1. No category

Advances learning
in pharmacy
practicE
objectives
Presented by: The CU Skaggs School of Pharmacy and Pharmaceutical Sciences
SATURDAY, FEBRUARY 22, 2014
Program Schedule
Advances in Pharmacy Practice: 2014
February 22, 2014
7:30 AM Sign‐in and Continental Breakfast
8:00 AM Announcements and Introductions
8:15 AM Immunizations 2014: What Pharmacists Can Do to Reduce Vaccinepreventable Disease
Wesley Nuffer, PharmD, CDE 9:15 AM 10:15 AM 10:30 AM 11:30 AM 12:30 PM 1:30 PM 2:30 PM 3:15 PM 3:30 PM 4:30 PM Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship
and Drug Development
Gerard Barber, RPh, MPH, FASHP Refreshment Break
Update on Current Medical Therapy for Diabetes
Michael McDermott, MD Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize
Progression and Complications
Sam Ellis, PharmD, BCPS, CDE Lunch
2014 Regulatory and Legislative Update: State and National Perspectives
Val Kalnins, RPh Drug Interactions Every Pharmacist Should Know
Daniel Malone, RPh, PhD Break
Evidence-based Treatment of Hypertension and High Blood Cholesterol:
Update on New Guidelines
Joseph Saseen, PharmD, FCCP, BCPS, CLS Program Evaluation and Wrap‐up
Learning Objectives
After attending each of the following presentations, participants should be able to:
Immunizations 2014: What Pharmacists Can Do to Reduce Vaccine-preventable Disease
ACPE# 0008‐0000‐14‐001‐L01‐P (1 contact hour – knowledge‐based) 1. Explain how vaccines and adjuvants stimulate the immune response and use this knowledge to recommend an appropriate immunization for a patient. 2. Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high‐dose, and different delivery systems) and outline vaccinations in the development pipeline. 3. List three steps that pharmacists can take to reduce the incidence of vaccine‐preventable diseases in their communities. Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship and Drug
Development
ACPE# 0008‐0000‐14‐002‐L01‐P (1 contact hour – knowledge‐based)
1. Describe the interplay of pathogen, host, and environment in the development of infectious disease and cite a recent example in which these elements were significant. 2. Citing at least one property of each, distinguish antimicrobial resistance from pathogen virulence. 3. Outline the purpose and multidisciplinary structure of an antimicrobial stewardship program and explain how pharmacists in outpatient and inpatient settings can promote appropriate antimicrobial usage. 4. Describe the potential indications and pharmacologic attributes of new antimicrobials currently in late‐stage development. Update on Current Medical Therapy for Diabetes
ACPE# 0008‐0000‐14‐003‐L01‐P (1 contact hour – knowledge‐based) 1. Explain the pathophysiology that underlies current therapies for type 1 and type 2 diabetes mellitus. 2. Given a patient case, describe how to individualize A1C targets and drug choices for that person. 3. Discuss practical aspects of initiating and adjusting old and new therapeutic agents for diabetes mellitus. Learning Objectives – continued
Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize Progression
and Complications
ACPE# 0008‐0000‐14‐004‐L01‐P (1 contact hour – knowledge‐based) 1. Outline the current evidence for the effectiveness of lifestyle interventions for the prevention or delay of progression to diabetes in patients who are at risk for diabetes. 2. Describe the non‐pharmacotherapeutic options to improve glucose control and reduce complications in patients with diabetes. 3. Given a profile of a patient with diabetes, provide two to three methods that a pharmacist could use to support the patient’s efforts to improve glucose control and subsequent diabetes complications. 2014 Regulatory and Legislative Update: State and National Perspectives
ACPE# 0008‐0000‐14‐005‐L03‐P (1 contact hour – knowledge‐based) 1. Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice of Pharmacy. 2. Summarize the latest developments in state and national initiatives and legislation related to pharmacy. 3. Describe the impact of FDA, DEA, and state board of pharmacy rules and proposed rules of 2012‐
2013. Drug Interactions Every Pharmacist Should Know
ACPE# 0008‐0000‐14‐006‐L01‐P (1 contact hour – knowledge‐based) 1. Describe the basic mechanisms for drug‐drug interactions. 2. Identify medications involved in clinically relevant interactions. 3. Given selected drug‐drug interactions, determine possible management strategies to minimize or avoid harm. Evidence-based Treatment of Hypertension and High Blood Cholesterol: Update on New
Guidelines
ACPE# 0008‐0000‐14‐007‐L01‐P (1 contact hour – knowledge‐based) 1. Describe the process for developing new hypertension, high blood cholesterol, and assessment of cardiovascular risk guidelines. 2. Review new guideline recommendations for the treatment of patients with hypertension and dyslipidemia. 3. List patient specific blood pressure goals and recommended treatments for patients with hypertension. 4. Identify patients who are eligible for statin‐based therapy and describe how they should be treated. Faculty
Conference Coordinators
Kathleen McCartney, PharmD Coordinator, Continuing Pharmacy Education University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Tonya Cook, PharmD, Clinical Pharmacy Specialist St. Mary’s Hospital Grand Junction, Colorado Brian Feagans, MS, RPh Pharmacy Clinical Manager St. Mary‐Corwin Hospital Pueblo, Colorado Brandi Koepp, PharmD, BCPS Pharmacy Clinical Coordinator Medical Center of the Rockies Loveland, Colorado Benton Westergaard Program Administrator, Continuing Pharmacy Education University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences Faculty – continued
Presenters
Gerard Barber, RPh, MPH, FASHP Coordinator P&T and Clinical Pharmacy Services, Co‐Chair, Pharmacy & Therapeutics Committee University of Colorado Hospital Samuel Ellis, PharmD, BCPS, CDE Associate Professor Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Denver Val Kalnins, RPh Executive Director Colorado Pharmacists Society Daniel Malone, RPh, PhD Professor College of Pharmacy University of Arizona Michael McDermott, MD Director Endocrinology and Diabetes Practice University of Colorado Hospital Wesley Nuffer, PharmD, CDE Assistant Professor Skaggs School of Pharmacy and Pharmaceutical sciences Joseph Saseen, PharmD, FCCP, BCPS, CLS Professor and Vice Chair Department of Clinical Pharmacy Professor, Department of Family Medicine CU schools of Pharmacy and Medicine Immunizations 2014: What Pharmacists Can Do to Reduce Vaccine-preventable
Disease
ACPE # 0008-0000-14-001-L01-P (1 contact hour – knowledge based)
Wesley Nuffer, PharmD, CDE
Assistant Professor
Department of Clinical Pharmacy
CU Skaggs School of Pharmacy and Pharmaceutical sciences
Learning Objectives
1. Explain how vaccines and adjuvants stimulate the immune response and use this knowledge to recommend
an appropriate immunization for a patient.
2. Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high-dose, and
different delivery systems)and outline vaccinations in the development pipeline.
3. List three steps that pharmacists can take to reduce the incidence of vaccine-preventable diseases in their
communities.
2/10/2014
Learning Objectives
• Explain how vaccines stimulate the immune response depending on vaccine type (live, inactivated, polysaccharide or conjugated) and use this knowledge to recommend an appropriate immunization for a patient
Immunizations 2014: What pharmacists can do to reduce vaccine‐preventable disease
Wesley Nuffer, PharmD, BCPS, CDE
February 22nd, 2014
Vaccine‐Mediated Immunity
http://www.historyofvaccines.org/content/how-vaccines-work
• Describe the latest developments for the influenza vaccine (trivalent vs. quadrivalent, high‐dose, and different delivery systems) and outline vaccinations in the development pipeline.
• List 3 steps that pharmacists can take to reduce the incidence of vaccine‐preventable diseases in their communities
Response to Disease
http://www.historyofvaccines.org/content/how-vaccines-work
1
2/10/2014
Polysaccharide Vaccines
• Stimulate B cells but not T cells
– “T‐cell independent”
– Less immunologic memory
– Lose “booster” effect
• Ineffective in immature immune system
– Children under 2 need conjugate
• Link to protein (tetanus, diptheria) to enhance immunity
• Now T cell immunity stimulated
Inactive and Live Vaccines
• Inactive vaccines won’t cause illness!
– Do not reproduce
– Utilize inert proteins/portions of the pathogen
– May administer inactive vaccines together Diptheria
• Live vaccines must reproduce to cause immunity
– Delay in immune response
– Theoretical risk to immunocompromised patients
– Dosing intervals may be relevant
• Can give two live vaccines simultaneously
• If not administered together, need to wait 28 days
Measles
Live vs Inactive Vaccines
Inactive Vaccines
Live Vaccines
- Live attenuated influenza
(LAIV)
- Herpes zoster
- Varicella
- Measles, mumps, rubella
- Rotavirus
- Yellow fever
- Oral typhoid
Influenza Vaccine
-
Inactivated influenza
Pneumococcal
Tdap & DTap
Hepatitis A
Hepatitis B
Human papillomavirus (HPV)
Inactive poliovirus
Meningococcal
Haemophilus influenzae
Rabies
Typhoid injection
1918 Influenza fears
2
2/10/2014
2013‐2014 Influenza Vaccine
• A/California/7/2009 (H1N1) pdm09‐like virus
• A (H3N2) virus antigenically like the cell‐propagated prototype virus A/Victoria/361/2011
• B/Massachusetts/2/2012‐like virus
• B/Brisbane/60/2008‐like virus (Quadrivalent only)
2014 Influenza Season
Influenza Vaccine without Eggs
• Development
– Isolation of the hemagglutinin (HA) protein
– No egg embryo or thimerosol used in production
– Contains HA protein of all three strains used for production
• Flublok
– Tri‐valent vaccine
– Approved in adults 18‐49 years old
– Shorter expiration date
• 16 weeks from the date of production
• Watch expiration date before administering
3
2/10/2014
High‐Dose Influenza Vaccine
• Provides same trivalent protection with 4x antigen load
• Indicated for people ≥ 65 years old
– Clinical studies demonstrate stronger antibody response – No data yet to show the vaccine leads to better illness protection
– On‐going study should answer effectiveness question in 2014‐15
• Higher adverse effects with high‐dose vaccine
– Local site reactions
– Headaches and fever
– Muscle aches
Alternate Delivery Routes & Devices
Alternative Vaccine Delivery Systems
• Intradermal devices
– Intradermal needles
– Needleless jet systems
• Oral delivery via encapsulation/stabilization
• Pulmonary delivery – Dry powder inhalers
– Nebulizers
– Intranasal delivery
• Micro needle delivery “Jet” System Vaccine Delivery
• Intradermal administration
– Delivers vaccine into the skin, rather than into muscle
• Smaller needle for delivery
• Less antigen required in preparation for similar efficacy
• Needleless “jet” systems
4
2/10/2014
Micro‐Needle Patch Delivery
Vaccines Under Development
•
•
•
•
•
•
•
•
•
•
•
HIV Tuberculosis
Salmonella
Hepatitis C
E Coli
Bioterrorism agents (anthrax, smallpox, ricin)
Epstein‐Barr
Malaria
Rabies
Streptococci group A & B
Cytomegalovirus
Nat Biotechnol 31, 1082-1085, 2013
Pharmacist’s Role: Beyond Influenza?
How many of you currently provide:
– S. Pneumoniae (Pneumovax)?
– Herpes Zoster (Zostavax)? – Hepatitis B?
– TdaP/Td?
– HPV?
– Meningococcal?
Pharmacist’s Role: Advocacy
Vaccine (Recommended population)
Vaccination rate (%)
Influenza (Age 50‐64)
44.5%
Influenza (Age >65)
66.6%
Influenza (HCP)
63.4%
Pneumococcal (High risk pts)
18.5%
Pneumococcal (Age >65)
59.7%
Tetanus in the past 5 years
52.3%
Hepatitis B
42.0%
Hepatitis B (HCP)
63.2%
Zoster (Age >60)
14.4%
National Health Interview Survey JAMA 3/2012
http://www.cdc.gov/flu/professionals/vaccination/vaccinecoverage.htm
5
2/10/2014
Pharmacist’s Role: Advocacy
Race/Ethnicity
Influenza (%)
Pneumococcal (%)
Hispanic
41.9%
39.0%
Black
56.1%
46.2%
White
67.7%
63.5%
Pharmacist’s Role: Education
• CDC resources
– MMWR listserv: www.cdc.gov/mmwr – Vaccine Information Statements (VIS)
• ACIP website
– http://www.cdc.gov/vaccines/acip/
– Vaccine schedules, catch‐up schedule, new recommendations
• Immunization Action Coalition (www.immunize.org)
National Health Interview Survey 2010
Vaccine Safety/Misinformation
– Good consumer information
– Resource for “hot topics”
Pharmacist’s Role: Safety
• Reporting of vaccine adverse events: VAERS
– www.vaers.hhs.gov
– Documentation of all patient‐reported adverse events
• Proper record keeping
The dangers of vaccinations to your child's long term health prospects and
longevity itself far outweigh any potential benefits touted by the pharmaceutical
industry for vaccines. The LIES and misinformation about vaccine benefits from the
drug industry is voluminous, overwhelming, and statistically provable. Don't allow
your child to go on the chopping block for these Liars and their profit margins. They
aren't working for you, they're servants of the corporate elite/Illuminati and the
Illuminati has a surreptitious population reduction agenda in place.
– Documentation of lot and expiration
– Providing proof of vaccination to patient
6
2/10/2014
Pharmacist’s Role: Vaccine Stability
Pharmacist’s Role: Vaccine Stability
Vaccine 2007; 25, 3980‐3986.
Pharmacist’s Role: Vaccine Delivery
• Accessibility
– See people when they’re “well”
– Adolescents
• Expertise
– Focus on patient‐care
– Decreasing distribution functions
• Public health emergencies
7
Infectious Disease Update: Trends in Antimicrobial Resistance, Stewardship and
Drug Development
ACPE # 0008-0000-14-002-L01-P (1 contact hour – knowledge based)
Gerard Barber, RPh, MPH, FASHP
Coordinator
P&T and Clinical Pharmacy Services,
Co-Chair, Pharmacy & Therapeutics Committee
University of Colorado Hospital
Learning Objectives
1. Describe the interplay of pathogen, host, and environment in the development of infectious disease and
cite a recent example in which these elements were significant.
2. Citing at least one property of each, distinguish antimicrobial resistance from pathogen virulence.
3. Outline the purpose and multidisciplinary structure of an antimicrobial stewardship program and explain
how pharmacists in outpatient and inpatient settings can promote appropriate antimicrobial usage.
4. Describe the potential indications and pharmacologic attributes of new antimicrobials currently in late-stage
development.
=
Disclosures
Thepresenterforthiscontinuingpharmacyeducation
activityreportsservingonthespeaker’sbureauforCubist
Pharmaceuticals.
• daptomycin
• nonbrandedantimicrobialstewardship
http://www.cdc.gov/drugresistance/threatreport2013/pdf/arthreats2013508.pdf
WhyisAntimicrobialResistance
Increasing?
Theenormousamountsofappropriate
&inappropriateantibioticusein
healthcareinstitutionsisthechief
culpritofantimicrobialresistancein
developedcountries?
EpidemiologicTriad
1. True
2. False
Environment
NumberofABXRX’es/1000inhabitantsin13
Europeancountries,1994&1997
Molstad,etal.ScandJInfectDis. 2002;34:366371.
HicksLA,etal.NEnglJMed2013;368:14611462
WebbBJ,etal.TransplProceed.2013:45:792297
Morbidity and Mortality Weekly Report (MMWR)
•MMWR
Notes from the Field: New Delhi Metallo--Lactamase–Producing Escherichia coli
Associated with Endoscopic Retrograde Cholangiopancreatography — Illinois, 2013
Weekly
January3,2014/62(51);10511051
InfectionswithcarbapenemresistantEnterobacteriaceae(CRE)*areincreasingamong
patientsinmedicalfacilities(1).CREthatproduceKlebsiellapneumoniaecarbapenemase
(KPC)havebeenresponsibleformuchoftheincreaseintheUnitedStates.However,New
Delhimetallolactamase(NDM)–producingCREhavethepotentialtoaddtothisburden.
Sincefirstreportedin2009,through2012,27patientswithNDMproducingCREhavebeen
confirmedbyCDCfromisolatessubmittedbystatelaboratories.SinceJanuary2013,atotal
of69patientswithNDMproducingCREhavebeenidentifiedintheUnitedStates;44
patientswerefromnortheasternIllinois.
ClinInfectDis.2006:42;647656.
RiskFactors
• ConcurrentSkin&SoftTissueInfection
• IVDA
PlacingtheNFL'sLawrenceTynes'MRSAProblemUnder
theMicroscope
ByDaveSiebert,MD
(FeaturedColumnist)onAugust30,2013
LawrenceTynes'PICCcanbeseeninhisrightarmasheholdsaplasticbulbfilled
withantibiotics.Courtesy:AmandaTynes'Twitter(@AmandaTynes9).
Source:
b/r
Areliableindicatorofapathogen’s
virulenceisitsresistanceto
antibiotics?
1. True
2. False
AntimicrobialCreep
VirulenceResistance
Virulence(Properties)
•
•
•
•
•
•
Resistance(perpanel)
Photobacteriumdamsela
Adhesion
Colonization
Invasion
Thermal,other,stabilities
Immuneresponsemodification
Toxinproduction
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Ami
Amp
Amp/sul
Cefz
Ceftx
Ceftz
Cip
Erta
Gent
Imi
Levo
Pip/taz
Tet
TMPSMX
Tobr
I
S
S
S
S
S
S
S
S
S
S
S
S
S
S
_______
BarberGR,etal.NEnglJMed2000;342:824
ByrneA,etal.CasesJournal 2009,2:9102
MechanismsofResistancetoAntibiotics
Genetic material from
external sources
(eg, plasmids)
Mutational events
Enzymatic inactivation
(eg, E-lactamase)
DNA replication
Topo
isomerase
Protein
mRNA
Nucleotide
biosynthesis
RNA
transcription
Efflux pumps
Decreased cell wall
permeability
Elimination or overproduction
of antibiotic target
AdaptedfromChopraI.CurrOpinPharmacol2001;1:464469
1.DecreasedPermeability:
• Cellwallchanges
• Porinchannelchanges
• Producebiofilms
Protein
synthesis
Ribosomal
protection
(eg, tet proteins)
mRNA
KeepingitSimple:
4MechanismsofResistancetoAntibacterialABX
2.ActiveEfflux:
• FQefflux
• Tetracyclineefflux
3.EnzymaticInactivation:
• lactamases
– Carbapenemases
• AGME
• Methylation
4.TargetSiteChanges:
• PBPs
• Ribosomalmodification
CDCDefinitionofCRE
• Resistanttoallofthefollowing3rd generation
cephalosporins:
Anon.ClinInfectDis.2010:50:10811083
Update
– Ceftriaxone
– Cefotaxime
– Ceftazidime
AND…
• Nonsusceptibletooneofthefollowing
carbapenems:
– Doripenem,Meropenem,orImipenem
CDCCREToolkit.
•MorbidityandMortalityWeeklyReport(MMWR)
•MMWR
Notes from the Field: Hospital Outbreak of Carbapenem-Resistant Klebsiella
pneumoniae Producing New Delhi Metallo-Beta-Lactamase
— Denver, Colorado, 2012
Weekly
February15,2013/62(06);108108
OnAugust16,2012,theColoradoDepartmentofPublicHealthandEnvironmentwas
notifiedoftwopatientsatanacutecarehospitalinDenverwithcarbapenemresistant
Enterobacteriaceae(CRE),specificallyKlebsiellapneumoniae (CRKP),isolatedfrom
respiratoryspecimensduringJuly–August.Both isolatesproducedNewDelhimetallobeta
lactamase(NDM).AreviewofmicrobiologyrecordsidentifiedathirdpatientwithNDM
producingCRKPisolatedfromarespiratoryspecimen,admittedinMay.Activesurveillance
culturesinSeptemberidentifiedanadditionalfivepatientscolonizedwithNDMproducing
CRKP.AninvestigationwaslaunchedbythehospitalandtheColoradoDepartmentofPublic
HealthandEnvironmenttoguideinfectioncontrolmeasuresandlimittransmission.
CREintheUS
• In2001,1.2%reportedatleastonecaseofCRE
toCDCviaNHSNorNNIS
• In2012,4.6%(181)ofallacutecarehospitals
(3918)reportedatleastoneCRE
– Rateforshortstayacutecarehospitals(n=145)was
3.9%
– Rateforlongtermacutecarehospitals(n=36)was
17.8%
– Rateshigherforhospitalswithmedicalschool
affiliationsandinhospitalswith>300beds
MMWR 2013;62:165170.
CREandMortality
• 58.8%casefatalityrateforICUpatients
• 7080%fatalityrateamongpatientswith
bacteremia
• Age,mechanicalventilation,malignancy,heart
disease,andICUstayhavebeenassociated
withincreasedmortalitywithCRE
• Removalofthefocusofinfectionwas
associatedwithsurvival
BilavskyE,etal.CurrOpinInfectDis23:327331.
GuptaN,etal.ClinInfectDis.2011;53:6067.
InfectionPrevention
• Reviewmicrobiologyrecordsforpreceding612
monthstoensurenocaseshavebeenseen
– Iffindacase,consideractivesurveillanceorprevalence
survey
• Handhygiene
• ContactPrecautions
– Performhandhygienebeforeandafterdonningagown
andgloves
– Donninggownandglovesbeforeenteringroom
– Removegownandglovespriortoexitingthepatient’s
roomandperformhandhygiene
• AntimicrobialStewardship(AMS)
MMWR.2009.58(10):25660.
Abouthandwashing…
Studiesshowthatthebestratesofappropriatehandwashing
techniqueamongseveralcliniciandisciplines(RN,MD,RPh,
etc.)areabout:
1.
2.
3.
4.
12%
25%
40%
60%
GoalsofAntimicrobialStewardship
GetSmartforHealthcare
Topics:
• Whyinpatientstewardship?
• Improvingstewardshipefforts–
tools/resources
• Evidencetosupportstewardshipefforts
• Resourcelibrary
(Adapted)
GoalsofAntimicrobialStewardship
ImprovingClinicalOutcomes
IMPROVEMENTMEASURES
•DecreaseLOS
•ImproveOrganism:ABXmatch
•Accuracyempiricregimens
•DecreaseOrganism:ABX
mismatch
•Rapidcorrectionof
mismatches
•Properdosing(includingPK/PD)
•ProperDOT
•FacilitateIVtoPO
• InpatienttoOPAT
•AppropriateABXD/Casindicated
n=300interventions
AVOIDANCE MANEUVERS
•Minimize“CollateralDamage”
•BacterialSuperinfection
Clostridiumdifficile
Stenotrophomonas sp.
•Fungalsuperinfection
•Waningactivityperantibiogram
•HospitalAcquiredInfection,other
•IncreaseLOS
KuhnS,etal.UCHABXMUE2012/13
32
Stewardshipoptimizespatientsafety:decreased
patientlevelresistance
Findings
Cmax/MIC
Criteria
Cipro
Standard
Antibiotic
duration
3 days
10 days
LOS ICU
9 days
Antibiotic
14%
resistance/
superinfection
ConcdependentABX:
AGs,quinolones
15 days
38%
T>MIC
TimedependentABX:
lactams
Studyterminatedearlybecauseattending
physiciansbegantotreatstandardcare
groupwith3daysoftherapy
SinghN,etal.AmJRespir Crit CareMed.2000;162:50511.
DoseOptimization
ExtendedInfusion,PiperacillinTazobactam
Amonginstitutionalantimicrobial
stewardshipprograms,whichofthe
followingpersonnelare,“keyplayers?”
1.
2.
3.
4.
5.
LodiseTP,etal.ClinInfectDis.2007;44:35763.
Infectiousdiseasephysicians
Pharmacists
Healthcareadministrators
Alloftheabove
1&2only
AMSProgram– KeyPlayers
• Administration,CSuite“Buyin”
• FormalCommitteeStructure
• PhysicianChampion(s)
– ID,Hospitalists,Hem/Onc
– Surgery– rare,butifwillingveryuseful
•
•
•
•
Pharmacy,specialtytrainingpreferred
IP(formerlyIC) – nursing,microbiology
QI/QA
Other– Informatics,SS/UR
AMSProgram– KeyComponents
•
•
•
•
•
•
•
•
Education
Prospectiveaudit– intervention&feedback
ABXrestriction,authorization
ABXordersets,Tx guidelines/pathways/CDSS
ABXoptimization
Streamlining/deescalation
IVtoPO
Monitoring– processesoutcomes
OwensJr,RC,AmbrosePG,NightingaleCH(Eds).AntibioticOptimization.2005
Dellit TH,etal.Clin InfectDis2007;44:159177.
TheCSuite…
Type:Administrator,MBA
$$$$Oriented
• RevenueGeneration
– MTMprograms
– Retail
• Costsavings
– ABXClass
– OverallABXBudget
–
UnpaidBeds
Type:MD,MPH,RN,RPh
MoreClinicallyOriented
• Outcomes
–
30dayReAdmits
–
LOS
–
MedicationSafety
– Meet,ExceedCore
Measures
Mustattach,alignwithtaskgroupsthataimtoimproveorganization
initiatives.Goodresults– especiallythoseviewedpubliclyusuallywellreceivedbyallCSuitetypes
Asshownbyinvitrotrials,minimizing
collateraldamagetofecalmicrobiotaisa
clearadvantageinsurotomycin’ssuccessin
limitingrelapseofClostridiumdifficile
associateddiarrhea?
1. True
2. False
OntheHorizon…
Surotomycinvs.Vancomycin
Surotomycin (PhaseIII)
Surotomycin
InPhaseIItrialvs vancomycin (n=199subjects):
• Proposedindication:Clostridiumdifficile diarrhea
• Oral,cycliclipopeptide
• 125mgor250mgpo BIDvsvancomycin 125mgpo
QID
• Eitherdoseregimen:noninferiortovancomycin
• Betterglobalcure(4weekspostlastdose)
– Lessrecurrenceateitherdose.StatisticallyNS;
– Seemswelltolerated.
Organism
(# isolates tested)
Bacteroides fragilis
group, including
DOT (21)
Prevotella spp.
(20)
Escherichia coli
(18)
Enterobacter spp
(18)
Klebsiella spp
(20)
MIC Range
Vancomycin
MIC90
MIC Range
MIC90
8,192
32 to 256
128
8,192
32 to 512
256
8,192
64 to 256
256
256 to 1,024
1,024
256 to 1,024
1,024
8,192 to > 8192
8,192 to >8,192
4,096 to >8,192
>8,192
> 8,192
DOT=distasonis,ovatus,thetaiotaomicron spp
MIC,MIC90inmcg/mL
PatinoH,et.al.51st ICAAC2011,Chicago,.IL:posterK205a
Adapted,Citron,etal.AAC 2012;56:16131615.
Agent Number
Chemical Name
(Company)
AFN-1252 (Affinium)
ABT-773 / cethromycin (originally
Abbott, Taisho, then Advanced Life
Sciences)
Study Phase
IIa (Acute skin, skinstructure
staphylococcal
infections)
MOA
Novel agent (Fabl-inhibitor).
Inhibits bacterial fatty acid
biosynthesis, targeting the
Fabl enzyme in staphylococci
[70].
Comments
Multicenter trials in US and
Canada for targeted oral
therapy of acute bacterial skin
and skin-structure (ABSSSI)
infections due to
staphylococci. Inactive
against streptococci including
enterococci and
Enterobacteriaceae.
III (moderate – severe Ketolide. Reversibly binds to Potent pneumococcal and
community-acquired the 50S subunit of the
atypical respiratory organism
bacterial pneumona) bacterial ribosome, blocking
activity, including macrolideprotein synthesis, preventing resistant strains. Oral
bacterial growth and
formulation; wide distribution
reproduction. Binds at 2 sites into pulmonary compartments
of bacterial ribosome
including epithelial lining fluid
compared with current
[71]. Like solithromycin,
macrolide agents binding at 1 additional side chain
site. (Note: solithromycin, a
structures / modifications
fluoroketolide discussed in
appear to ameliorate CNS
detail, binds at 3 sites and has adverse effects of
iv and po formulations).
telithromycin (lacks
telithromycin’s pyridineimidazole side chain) and
necessitate additional bacteria
mutations to effect resistance.
Has FDA orphan-drug-status
for prophylaxis in patients
exposed to inhalational B.
anthracis (anthrax) tularemia
Agent Number
Chemical Name
(Company)
BC-3881 (Nabriva Therapeutics)
Study Phase
II (Acute Bacterial
Skin and Skin
Structure Infections)
MOA
Novel pleuromutilin
antimicrobial; inhibits
bacterial protein synthesis
by interaction with 23S rRNA
of the 50S bacterial
ribosome subunit. Potent in
vitro activity against common
Gram-positive skin organisms
including S. aureus (MSSA
and MRSA), coagulasenegative Staphylococcus spp.
Streptococcus agalactiae, and
S. pyogenes. Also exhibits in
vitro activity against a broad
spectrum of Gram-positive and
gram-negative community
respiratory pathogens
including S. pneumoniae,
including Moraxella catarrhalis
and Haemophilis influenza as
well as atypical bacteria,
Legionella pneumophila,
Chlamydia pneumoniae, and
Mycoplasma pneumonia [74].
Comments
Intravenous formulation dosed
q12h in first human ABSSSI
trial (duration 5 – 14 days).
Previously utilized in veterinary
medicine or topical use in
humans (retapamulin,
Altargo®, Altabax® GlaxoSmith Kline) due to toxicity. In
ABSSSI demonstrated
comparable clinical success to
vancomycin. Relatively welltolerated among 141 subjects,
most frequent AEs were
headache, nausea, and
infusion site phlebitis.
Expected to move to Phase III
trials.
Agent Number
Chemical Name
(Company)
Study Phase
ACT-179811 / Cadazolid (Actelion)
III (C. difficileassociated diarrhea)
ACHN-975 (Achaogen)
I (safety, doseescalation trial)
MOA
Novel chimeric quinolonyloxazolidinone; having structural
elements of both quinolones
and oxazolidinones [77].
Novel, LpxC-inhibitor. LpxC-1
is an inhibitor of LpxC, a
deacetylase enzyme present
in many Gram-negative
bacteria [73].
Comments
In vitro studies show
bactericidal effect against C.
difficile. [Sweden] Phase II
dose escalation trials (n=84)
comparing cadazolid
suspension, 250mg, 500mg,
and 1g twice daily versus
vancomycin 125mg po 4-times
daily. Clinical cure rates, all
doses, non-inferior to
vancomycin, similar rates of
TEAE. Sustained clinical cure,
4 weeks from last dose,
favored cadazolid which was
as effective at 250mg dose as
1g doses.
Subcutaneous injection in
murine models infected with
MDR-Acinetobacter baumannii
do not actively kill or stunt
bacterial growth, but stunt
endotoxin production and the
subsequent ability of the
bacteria to activate the sepsis
cascade. Development to
target MDRO-gram-negatives
including MDR-Pseudomonas
aeruginosa.
Summary
Bugsvs.Humans
• “Bugs”herelongerthanhumans
– Moreofthem,lotsmorethanus
• Adapt,generatemuchmorequickly
• Noveldrugtomarket:~$1billion
• Antimicrobialstewardshipiscritical
– Selectivity:lotsof“goodbugs,”neededbugs
– Allaspects,trulymultidisciplinary
– Institutional,community,agricultural
• Timewilltell…
BarberGR.AmJHospPharm.2005;62:1143[Editorial]
LevySB.TheAntibioticParadox.2002.Perseus2nd ed.Cambridge,MA
WhyisAntimicrobialResistance
Increasing?
• SusceptibleHosts
• Lackofbasicinfectioncontrolmeasures
• SelectivepressuresABXuse
– Appropriate&inappropriate
• Unrecognizedcolonization
• Unrecognizedreservoirs(environmental)
• Movementofpatients,HCWs
– HospitalSNF,LTAC
– Hospital
Community
• LackofnovelmechanismABXspast3decades
Update on Current Medical Therapy for Diabetes
ACPE # 0008-0000-14-003-L01-P (1 contact hour – knowledge based)
Michael McDermott, MD
Director
Endocrinology and Diabetes Practice
University of Colorado Hospital
Learning Objectives
1. Explain the pathophysiology that underlies current therapies for type 1 and type 2 diabetes mellitus.
2. Given a patient case, describe how to individualize A1C targets and drug choices for that person.
3. Discuss practical aspects of initiating and adjusting old and new therapeutic agents for diabetes mellitus.
Disclosure
Michael McDermott MD
Type 2 Diabetes Mellitus
2014
No Conflict of Interest to Disclose
Michael T. McDermott MD
Director, Endocrinology and Diabetes Practice
University of Colorado Hospital
[email protected]
Talk Objectives
Diabetes Mellitus
Diagnosis 2014
1. Explain the pathophysiology that underlies current
therapies for type 1 and type 2 diabetes mellitus.
2. Emphasize the importance of individualization of
A1C targets and drug choices.
3. Discuss practical aspects of initiating and adjusting
old and new therapeutic agents for diabetes mellitus
Diabetes Mellitus
Fasting Glucose > 125 mg/dl
2 Hour PP Glucose > 200 mg/dl
A1C > 6.5%
Pre-Diabetes
Fasting Glucose: 100-125 mg/dl
2 Hour PP Glucose: 140-200 mg/dl
A1C: 5.7-6.4%
Consensus Recommendation: ADA, EASD, IDF 2009
Diabetes Mellitus
Diabetes Mellitus
28 Million Americans
Projection through 2033
5%
Type 2 DM
Type 1 DM
2033
Leading US Cause
Myocardial Infarction
Kidney Failure
Amputations
Blindness
2014
95%
1 New Case Every 17 Seconds
5,000 New Cases Every Day
2,000,000 New Cases Every Year
Huang ES, Diabetes Care 2009; 32:2225-9
1
Pre‐Diabetes
Food Consumption
79 Million Americans
Density of One US Fast Food Chain
Progression to Type 2 Diabetes
11% per Year
Prevention of Progression
Lifestyle Measures:  60%
Metformin:  30%
DPP Research Group. N Engl J Med 2002; 346:393-403. DPP Study
Tuomilehto J, N Engl J Med 2001; 344:1343-50. Finnish Study
Pan XR, Diabetes Care 1997; 20:537-44. Da Qing Study
Lack of Exercise
Obesity
Lack of Exercise
The Evolution of Man
2
Diet
Exercise
Ideal Diet for DM:
No Consensus
Walk 30 Minutes Daily
Mediterranean May Be Best
Main Goal
Calorie Restriction
-130 kcal/day
1 lb = 3500 kcal
Deficit: 500 kcal/day
Loss of 1 lb/week
Loss of 52 lb/year
“Well, the Parkers are dead.
You had to encourage them to
take thirds, didn’t you?”
Weight Loss
Loss of 1 lb in 27 days
Loss of 14 lb in 1 year
The 100 Meter Mosey
Type 2 Diabetes Mellitus
SGLT2 Inhibitors
Medication Development
Bromocriptine
Colesevelam
DPP4 Inhibitors
Pramlintide
GLP-1 Analogs
Meglitinides
Glucosidase Inhibitor
Thiazolidinediones
Basal Insulins
Rapid Acting Insulins
3500 kcal = 1 lb
Insulin
1920
Sulfonylureas
1960
Metformin
1990
2000
Type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus
Pathophysiology
Pathophysiology Based Therapy
 Glucose
Production
 CNS Effect
Insulin
Secretion
 CNS Effect
 Glucose
Production
Bromocriptine
Metformin
Hyperglycemia
Thiazolidinedione
Insulin
Secretion
Sulfonylurea
Meglitinide
Euglycemia
SGLT-2
Inhibitor
 Insulin
Resistance
 Incretin
Effect
 Insulin
Resistance
2010
GLP-1 Analog
DPP4 Inhibitor
 Incretin
Effect
 Glycosuria
Bile Acid
Resin
Glucosidase
Inhibitor
 Glucose
Absorption
3
Incretin Physiology
 Glucose
Production
 Appetite
 Satiety
 Insulin
 Glucagon
 Gastric
Emptying
Glucose
Dependent
L-Cells
GLP-1
T1/2 = 2 min
Due to DPP4
GLP-1 = Glucagon Like Peptide-1
DPP4 = Dipeptidyl Peptidase 4
Incretin Based Therapy
Incretin Based Therapy
(7-36)
T ½ : 1-2 min
GLP-1
(9-36)
[DPP4]
Inactive
GLP‐1 Analog / Agonist
 Resistant to DPP4 Action
 Prolonged Duration of Analog Action
DPP4 Inhibitor
 Prevents Native GLP-1 Breakdown
 Prolongs Duration of Native GLP-1 Action
Sodium Glucose Transporter 2 Inhibitors
Kidneys Filter + Reabsorb
Glucose: 180 g/day
90% through SGLT2
GLP-1 Analog: DPP4 Resistant
Exenatide (Byetta)
Liraglutide (Victoza)
Exenatide QW (Bydureon)
Dipeptidyl
Peptidase 4
GLP-1
Normal
SGLT2 Inhibitor
Glucose Loss
80-100 g/day
320-400 kcal/day
DPP4 Inhibitor: Inhibit GLP-1 Breakdown
Sitagliptin (Januvia)
Saxagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)
Sodium Glucose Transporter 2 Inhibitors
Generic
Canagliflozin
Dapagliflozin
Empagliflozin
Luseogliflozin
Ertugliflozin
Ipragliflozin
Tofogliflozin
ISIS 388626
EGT 1747
LX 4211
Trade Name
Invokana
Farxiga
NA
NA
NA
NA
NA
NA
NA
NA
Doses
100, 300 mg
5 mg
Glycosuria
Glycosuria
BG > 180 mg/dl
BG > 80 mg/dl
Colesevelam
Mechanism: Impairs Glucose Absorption
Target: Postprandial Glucose
Efficacy:  A1C ~ 0.5%
Name Brand: Welchol (625 mg tabs)
 Glucose
Absorption
Dose: 3 Tabs BID or 6 Tabs QAM
Additional Benefit: LDL Reduction ~20%
Cost per Month: $225
4
Bromocriptine
Mechanism: Reduces Insulin Resistance by
Enhancing CNS Dopaminergic Tone
Target: Postprandial Glucose
Efficacy: Monotherapy  A1C 0.4-0.6%
Enhances
Add-on Therapy  A1C 0.6-0.9% Dopaminergic
Tone
Name Brand: Cycloset (0.8 mg tabs)
Start: 1 Tab QAM
Titrate:  Weekly by 1 Tab to total dose of
2-6 Tabs (1.6 – 4.8 mg) QAM
Cost per Month: $299
Case History
Personalized Diabetes Care
Individualize
A1C Goal
Medications
Ismail-Beigi F, Ann Intern Med 2011;154:554-9
Inzucchi S, Diabetes Care 2012; 35:1364-79
Riddle M, Diabetes Care 2012;35:2100-7
Case History
HPI: 35 y.o. man with DM2 x 1 years
PMH: HTN
Lifestyle Modification: Emphasized
DM Meds: Metformin 2000 mg
PE: Ht 5’11” Wt 236 lb BP 132/82 P 74
Lab: A1C 7.8% SMBG: FBG 95-130
HPI: 78 y.o. woman with DM2 x 20 years
PMH: CAD, CHF, A Fib
Lifestyle Modification: Emphasized
DM Meds: Metformin 1000 mg
PE: Ht 5’6” Wt 157 lb BP 139/78 P 94
Lab: A1C 7.9%, Cr 0.7 SMBG: FBG 88-155
What is your target A1C for this patient?
A. < 6%
B. < 6.5%
C. < 7%
D. < 7.5%
E. < 8%
What is your target A1C for this patient?
A. < 6%
B. < 6.5%
C. < 7%
D. < 8%
E. < 9%
Personalized A1C Goal
A1C Goal < 7%
Recent Onset
No / Minimal Hypoglycemia
A1C Goal < 7.5% or < 8%
Known Cardiovascular Disease
Frequent Hypoglycemia
Short Life Expectancy
Advanced Age
Ismail-Beigi F, Ann Intern Med 2011;154:554-9
Inzucchi S, Diabetes Care 2012; 35:1364-79
Riddle M, Diabetes Care 2012;35:2100-7
Case History
HPI: 65 y.o. man with DM2 for 18 years. He has CAD
with 2 prior MI and moderate CHF. He fears having
hypoglycemic episodes, like he has had in the past.
DM Meds: Metformin 2000 mg
PE: Ht 6’0” Wt 223 lb BP 138/86 P 92
Lab: FBG 108-163 A1C 8.2% eGFR > 60
Lifestyle modification is strongly emphasized. What
medication would be least likely to cause hypoglycemia?
A. Basal Insulin
B. Mealtime Insulin
C. Sulfonylurea
D. Meglitinide
E. GLP-1 Analog
5
Case History
HPI: 57 y.o. woman with DM2 for 6 years. She is most
concerned about additional weight gain.
DM Meds: Metformin 2000 mg
PE: Ht 5’6” Wt 232 lb BP 132/82 P 82
Lab: FBG 122-173 A1C 8.0%
Personalized Diabetes Care
Individualize
A1C Goal
Lifestyle modification is strongly emphasized. What
medication would be least likely to cause weight gain?
A. Sulfonylurea
B. Thiazolidiendione
C. DPP4 Inhibitor
D. Basal Insulin
E. Mealtime Insulin
Type 2 Diabetes: Personalized Medication Choices
BG Target
FBG > PPBG
Metformin
Thiazolidinedione
Basal Insulin
PPBG > FBG
Sulfonylurea
DPP4 Inhibitor
GLP-1 Analog
SGLT-2 Inhibitor
Meglitinide
Glucosidase Inhibitor
Bile Acid Resin
Bromocriptine
Pramlintide
Prandial Insulin
Effect
Low BG Weight
Medications
Type 2 Diabetes Mellitus: Personalized Management
Cost
Lifestyle Intervention
++
++
+++
No
No
Yes
--

+
++
++
++
+
++
+
+
+
+
+
+
+++
Yes
No
No
No
Yes
No
No
No
No
Yes

--


------

+
+++
+++
+++
++
++
+++
+++
+++
++
+
Metformin
3 MOS A1C > Goal  Add:
GLP-1
Analog
DPP4
Inhibitor
SGLT-2
Inhibitor
Basal
Insulin
TZD
SU
Wt Loss
No Hypo
Wt Neutral
No Hypo
Wt Loss
No Hypo
Most
Effective
No
Hypo
Low
Cost
Bile Acid
Resin
Glucosidase
Inhibitor
Bromocriptine
Pramlintide
Basal/Bolus
Insulin
No
Hypo
Wt Loss
No Hypo
Most
Effective
LDL
Reduction
No
Hypo
MTM adapted from Inzucchi S, Diabetes Care 2012; 35:1364-79
Emergency Hospitalizations for Adverse Drug Events
Older U.S. Adults, 2007–2009
Hypoglycemia
Veterans
Hypoglycemia in DM2
2 x  Risk CV Events
ACCORD
Hypoglycemia in DM2
 Mortality Rate
Zhao Y
Seaquist E
DM1 and DM2
Hypoglycemia
3.4 x  Risk Mortality
McCoy R
Budnitz DS,N Engl J Med 2011;365:2002-12
Zhao Y, Diabetes Care 2012; 35:1126-32
Seaquist E, Diabetes Care 2012; 35:409-14
McCoy R, Diabetes Care 2012; 35:1897-1901
6
DM2 Medications: Hypoglycemia
DM2 Medications: Weight Change
Hypoglycemia
Rare Hypoglycemia
Weight Gain
Weight Neutral Weight Loss
Insulin
Meglitinide
Sulfonylurea*
Metformin*/**
DPP4 Inhibitor**
Bromocriptine**
Bile Acid Resin**
Glucosidase Inhibitor**
GLP-1 Analog***
SGLT-2 Inhibitor***
Pramlintide***
Thiazolidinedione
Thiazolidinedione
Insulin**
Meglitinide**
Sulfonylurea*/**
Metformin*
DPP4 Inhibitor
Bile Acid Resin
Bromocriptine
* Inexpensive
** Weight Neutral
*** Weight Loss
GLP-1 Analog
SGLT-2 Inhibitor
Pramlintide
* Inexpensive
** Hypoglycemia
Case History
HPI: 48 y.o. man with DM2 x 2 years. CKD from HTN.
DM Meds: Metformin 2000 mg, Sitagliptin 50 mg
PE: Ht 6’5” Wt 264 lb BP 142/95 P 80
Lab: FBG 86-122 Creatinine 1.7 eGFR 51 A1C 6.6%
Lifestyle modification is again emphasized.
What would you now recommend?
A. Stop Metformin; Start Basal Insulin
B. Reduce Metformin dose; Start GLP-1 Agonist
C. Reduce Metformin dose; Continue Sitagliptin
D. No Change in Therapy
E. Low Carbohydrate Diet
Metformin Use In People With CKD
eGFR
> 60
Action
Full Dose Metformin Appropriate
Monitor Renal Function Annually
45-59
Full Dose Metformin Appropriate
Monitor Renal Function Q 3-6 Months
30-44
Half Dose Metformin With Caution
Monitor Renal Function Q 3 Months
< 30
Stop / Avoid Metformin
Lipska KJ. Diabetes Care 2011; 34: 1431-7
Inzucchi S, Diabetes Care 2012; 35: 1364-79
Insulin
Ekstrom N, BMJ 2012; ePub ahead
Insulin Preparations
The Big Gun
Insulin
Onset
Lispro
5-15 min
Aspart
10-20 min
Glulisine 5-20 min
Glargine 1-4 hr
Detemir
1-4 hr
Regular 30-60 min
NPH
1-4 hr
Mixes
Peak
1-2 hr
1-3 hr
1-3 hr
none
none
2-4 hr
8-12 hr
Duration
3-5 hr
3-5 hr
3-5 hr
22-24 hr
20-24 hr
6-8 hr
12-20 hr
7
Basal Insulin Therapy
Insulin Pharmacokinetics
Indications
Lispro / Aspart / Glulisine
Glargine / Detemir
Regular
NPH
1-2 hr
 Ketonuria / Ketonemia
8-12 hr
+/- 24 hr
+/- Peakless
4-5 hr
 FBG > 250 mg/dl
 Random BG > 300 mg/dl
2-4 hr
Insulin
Injection
 A1C > 11%
6-8 hr
12-16 hr
 Weight Loss, Polydipsia, Polyuria
24 hr
 A1C > Goal on 1‐3 Oral Agents
Basal Insulin Therapy
Basal Insulin Therapy
Initiate and Titrate
Adjusting Basal to Control AM FBG
Glargine / Detemir / NPH HS
Start: 10-25 U Daily
Check: FBG x 2-3 Days
Goal:
AM FBG 80-130
Glargine / Detemir / NPH HS
Based on AM FBG, Adjust (choose):
Mean AM
FBG
Adjust Adjust Adjust Adjust Adjust
> 130
1U 2U 3U 4U 5U
No 
No 
No 
No 
No 
80-130
Average Basal Dose (DM2)
0.4-0.5 U/kg or 0.25 U/lb
+/- 24 hr
Summary
Start: 10-25 U Daily
Titrate:  by 1-5 U every 2-3 days until AM FBG 80-130
Mealtime Insulin Therapy
Basal Plus Insulin
Indications
Initiate and Titrate
Lispro / Aspart / Glulisine
 A1C > Goal – AM FBG at Goal
Start: 4-10 U at Largest Meal (Dinner Usually)
Titrate: Check BG at Bedtime or Before Next Meal
 PPBG > Goal – AM FBG at Goal
Depending on Meal Covered, Adjust Until:
HS BG < 140 mg/dl, OR
BG before Next Meal < 130 mg/dl
Next (if needed): Add Bolus at 2nd Largest Meal
Next (if needed): Add Bolus at 3rd Meal
8
Basal Plus Insulin
Basal Plus Insulin
Adjusting Bolus Insulin at Dinner
Adjusting Bolus Insulin at Lunch
Goal:
HS BG < 140
B
L
D
Bed
Goal:
Pre-Dinner BG < 130
B
L
D
Bed
Alternative Goal: 2 Hr PPBG < 180 mg/dl
Alternative Goal: 2 Hr PPBG < 180 mg/dl
Basal Bolus Insulin
Basal Bolus Insulin
Initiate and Titrate
Adjusting Bolus with Each Meal
Lispro / Aspart / Glulisine
Goal:
Next Pre-Meal BG < 130
Start: 4-5 U at Each Meal
Titrate: Check Pre-Meal BG and HS BG Daily
Goal:
HS BG < 140
Adjust Until:
BG before Each Meal < 130 mg/dl, AND
HS BG < 140 mg/dl
Consider: Carbohydrate Counting / Flexible Dosing
Using C:I Ratio and Correction Factor (CF)
B
L
D
Bed
Alternative Goal: 2 Hr PPBG < 180 mg/dl
Goal:
AM FBG 80-130
Average Total Daily Dose (DM2)
0.8-1.0 U/kg or 0.4 U/lb
Obesity Treatment as DM2 Strategy
Phentermine / Topiramate (Qsymia)
Medications – FDA Approved
Weight Effects
Phentermine:  appetite
Phentermine / Topiramate (Qsymia):  appetite
Lorcaserin (Belviq):  appetite
Orlistat (Xenical, Alli):  fat absorption
GLP‐1 Analogs:  appetite [DM2]
SGLT2 Inhibitors:  urine glucose [DM2]
Wt Loss
10-12%
Indications:
BMI > 30 kg/m2
BMI > 25 kg/m2 with obesity related disease
Gadde K, Lancet 2011; 16;377(9774):1341‐52
9
Phentermine / Topiramate (Qsymia)
Phentermine / Topiramate (Qsymia)
Glucose Effects
Clinical Notes
743 Patients (BMI 27-45):
Prediabetes (292), Metabolic Syndrome (451)
RCT: Q 7.5/46 mg, Q15/92 mg, or Placebo (Lifestyle) x 108 weeks
Qsymia Qsymia
Lifestyle
7.5/46 mg 15/92 mg + Placebo
 Combination: greater efficacy, fewer side effects
 Weight Loss: 10‐12% (20‐24 lb for 200 lb person)
 Doses (Phentermine / Topiramate): 3.75/23 mg, 7.5/46 mg, 15/92 mg
Weight Loss
10.9%
12.1%
DM2 Prevention
70.5%
78.7%
2.5%
 Cost: $150.00/month
 Off‐Label: use of generic Phentermine + Topiramate
Garvey WT, Diabetes Care 2013;doi:10.2337/dc13-1518 (e-pub)
Lorcaserin (Belviq)
Weight Effects
Lorcaserin (Belviq)
Glucose Effects
604 DM2 Patients (BMI 27-45):
RCT: Lorcaserin 10 mg QD vs 10 mg BID vs Placebo x 1 Year
Wt Loss
4-5%
Smith SR, N Engl J Med 2010;363:245‐56
Lorcaserin (Belviq)
Clinical Notes
 Serotonin 2C Receptor Agonist  Satiety
 Weight Loss: 4‐5% (8‐10 lb for 200 lb person)
 Previous Serotonin Agonists: Dexfenfluramine +
Fenfluramine caused cardiac valve disease
 2C Receptor: in Brain only and not in Heart
 Lorcaserin: No Evidence of Heart Valve Disease  Cost: $?/month
 Off‐Label: Use with Phentermine (unclear safety)
O'Neil PM, Obesity 2012; 20:1426-36
Treatment of Obesity
Bariatric Surgery
Multiple Surgery Types Available
Indications:
BMI > 40 kg/m2
BMI > 35 kg/m2 with obesity related disease
10
Bariatric Surgery
Bariatric Surgery
Weight Loss – 15 Years
Mortality – 15 Years
Hazard Ratio
(Adjusted)
0.71 (p=.01)
 29%
Control
Banding 14%
Vertical Banded
Gastroplasty 16%
Gastric Bypass 25%
Study of Obese Subjects (SOS)
Sjostrom L. N Engl J Med 2007;357:741-52
Study of Obese Subjects (SOS)
Sjostrom L. N Engl J Med 2007;357:741-52
Bariatric Surgery
Bariatric Surgery
Mortality Rate: < 1%
Adverse Events: ~ 20%
Beneficial Effects:
Randomized Trial: 43 Obese Patients with DM2
Roux-en-Y Surgery vs Intensive Lifestyle and Medications
One Year Follow-up
Roux-en-Y
Surgery






Lifestyle +
Medications
Weight Loss
25.8%
6.4%
DM2 Remission
60%
6%
Buchwald, JAMA 2004; 292:1724
Maggard, Ann Intern Med 2005; 142:547
DeMaria E, NEJM 2007; 356:2176
Sjostrom L, NEJM 2007; 357:741
Cummings D, Obesity Week 2013, Nov; Abstract T-66
EndoBarrier
Cardiovascular Disease
Diabetes Mellitus
Hyperlipidemia
Hypertension
Sleep Apnea
Mortality
Summary of Type 2 Diabetes Management








Obesity is the most important risk factor for DM2
Lifestyle modification can prevent DM2 and must be
part of all DM2 management plans
DM2 results from excess hepatic glucose production,
insulin resistance and relative insulin deficiency
Medications are available to address the multiple
known pathophysiological factors in DM2
A1C < 7% prevents microvascular complications
Hypoglycemia should be avoided
Glycemic goals and therapy should be personalized
Obesity treatment beneficial for DM2 managment
11
Thank You
Appendix
Type 2 Diabetes Mellitus
Prevention and Treatment
Diet
Lifestyle Modification
 No consensus regarding ideal diet for DM
 Main Goal: Calorie Restriction
 1 lb = 3500 kcal
 500 kcal/d deficit = 1 lb/week = 52 lb/year
Exercise
 Walk 30 min/day ~ 130 kcal
 130 kcal/d deficit = 1 lb/27 days = 14 lb/yr
Weight Loss
Metformin
Mechanism:
 Reduce insulin resistance (liver > muscle)
 Reduce hepatic glucose production
Products available
 Metformin
 Glucophage XR
 Glumetza
Start: 500 mg qd short acting preparation;
 weekly to 2000-2500 mg qd (BID dosing)
Start: 1000 mg qd long acting preparation;
 to 2000 mg qd in 1-2 weeks (QD dosing)
Avoid: eGFR < 30 ml/min; Severe liver disease
Sulfonylureas
Thiazolidinediones
Mechanism:
 Reduce insulin resistance (fat, muscle, liver)
Products available
 Pioglitazone (Actos)
 Rosiglitazone (Avandia)
Start: low or middle dose;  every 4-6 weeks,
as needed, to highest dose
Avoid: Class 2-4 CHF; significant edema;
Liver disease (except NASH)
Caution: Chronic renal failure (edema)
Bladder cancer
Mechanism: stimulate insulin secretion
Products available



Glyburide
Glipizide, Glipizide XL/ER
Glimepiride (Amaryl)
Start: low,  to maximum dose, as needed
Avoid: Chronic renal failure (Glipizide OK)
12
Meglitinides
Mechanism: stimulate insulin secretion
Products available


Repaglinide (Prandin)
Nateglinide (Starlix)
Start: lowest dose before each meal;
 to highest dose TID, as needed
Avoid: Chronic renal failure (Repaglinide OK)
Amylin Based Therapy
Mechanism: Glucagon Suppression
Postprandial Glucose Reduction
Products available

Incretin Based Therapy
Mechanism: Glucose-dependent Insulin Stimulation
Glucose-dependent Glucagon Suppression
GLP-1 Analog / Agonist
Exenatide (Byetta): Start 5 mcg BID;  to 10 mcg BID in 1 month
Liraglutide (Victoza): Start 0.6 mg QD,  to 1.2 mg QD in 2 wks,
 to 1.8 mg QD in 2 wks
Exenatide QW (Bydureon): 2 mg QW
DPP4 Inhibitor
Sitagliptin (Januvia): 100 mg QD (  dose in renal failure)
Saxagliptin (Onglyza): 2.5 or 5 mg QD (  dose in renal failure)
Linagliptin (Tradjenta): 5 mg QD (no dose change in renal failure)
Alogliptin (Nesina): 25 mg (  dose in renal failure)
Flexible Mealtime Bolus Insulin
Bolus Components
C:I Ratio: Gm of Carb covered by 1U Insulin
CF: Expected BG drop from 1U Insulin
Add if pre-meal BG high
Pramlintide (Symlin)
Type 1 DM:
Starting Calculations at UCH
Start 15 ug TID.  q 3 days to 30 ug TID,
C:I = 500/TDD (~15:1) CF = 1650/TDD (~50:1)
to 45 ug TID, and to 60 ug TID.
Type 2 DM:
Start 60 ug TID.  in 3-7 days to 120 ug TID.
Goal for Dose Adjustment
2 Hr PPBG < 180 mg/dl or
Next Pre-meal BG < 130 mg/dl or
PPBG 30-50 mg/dl above Pre-meal BG
13
Improving Outcomes from Pre-diabetes to Diabetes: Strategies to Minimize
Progression and Complications
ACPE # 0008-0000-14-004-L01-P (1 contact hour – knowledge based)
Samuel Ellis, PharmD, BCPS, CDE
Associate Professor
Skaggs School of Pharmacy and Pharmaceutical Sciences
University of Colorado Denver
Learning Objectives
1. Outline the current evidence for the effectiveness of lifestyle interventions for the prevention or delay of
progression to diabetes in patients who are at risk for diabetes.
2. Describe the non-pharmacotherapeutic options to improve glucose control and reduce complications in
patients with diabetes.
3. Given a profile of a patient with diabetes, provide two to three methods that a pharmacist could use to
support the patient’s efforts to improve glucose control and subsequent diabetes complications.
DisclosureStatement
Improving Outcomes from
Pre-diabetes to Diabetes:
– Ihavenorelevantfinancialrelationshipswithcommercialinterests
pertainingtothecontentpresentedinthisprogram.
Strategies to Minimize Progression and Complications
February22,2014
Sam Ellis, PharmD, BCPS, CDE
Associate Professor
University of Colorado Skaggs School of Pharmacy
and Pharmaceutical Sciences
Objectives
1.
Outlinethecurrentevidencefortheeffectivenessoflifestyle
interventionsforthepreventionordelayofprogressiontodiabetesin
patientswhoareatriskfordiabetes.
2.
Describethenonpharmacotherapeuticoptionstoimproveglucose
controlandreducecomplicationsinpatientswithdiabetes.
3.
Givenaprofileofapatientwithdiabetes,provide23methodsthata
pharmacistcouldusetosupportthepatient’seffortstoimprove
glucosecontrolandsubsequentdiabetescomplications.
Questions:
Take23minutesandthinktobrainstorm
Q1:Whatdoyoudoforyourpatientswithdiabetes?
Q2:Whatshouldwebedoingforourpatientswith
diabetes?
Age-Adjusted Prevalence of Obesity and Diagnosed
Diabetes Among U.S. Adults Aged 18 Years or older
DiabetesPrevention
Obesity (BMI 30 kg/m2)
1994
• RoleofDiet
• RoleofExercise
• RoleofMedications
No Data
Diabetes
2010
2000
<14.0%
1994
14.0-17.9%
18.0-21.9%
22.0-25.9%
>26.0%
2010
2000
No Data
<4.5%
4.5-5.9%
6.0-7.4%
7.5-8.9%
>9.0%
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at
http://www.cdc.gov/diabetes/statistics
DefiningPreDM:Categoriesof
IncreasedRisk
A1c Values
Impaired fasting glucose Impaired glucose tolerance
PrevalenceofPrediabetesintheUS
In20052008:
• 35%ofU.S.adultsaged20yearsorolderhad
prediabetes
• 50%ofthoseaged65yearsorolderhadprediabetes
• ApplyingthispercentagetotheentireU.S.
populationin2010yieldsanestimated79million
Americansaged20yearsorolderwithprediabetes.
ADAcriteriafortestingfordiabetesin
asymptomaticpatients
1. Alladultswhoareoverweight(BMI25)andhave
1ormoreadditionalriskfactors
– Physicalinactivity
– Firstdegreerelativewithdiabetes
– Highriskrace/ethnicity(e.g.,AfricanAmerican,Latino,Native
American,AsianAmerican,PacificIslander)
– Womenwhodeliveredbaby>9lbsorwithGDM
– HTN
– HDL<35mg/dLand/orTG>250mg/dL
– WomenwithPCOS
– A1C5.7%,IGT,orIFGonprevioustest
– Otherconditionsassociatedwithinsulinresistance
– HistoryofCVD
StudytoPreventDiabetes:Diabetes
PreventionProgram(DPP)
x Topreventordelaythedevelopmentof
type2diabetesinpersonswithimpaired
glucosetolerance(IGT)
Knowler WC, et al. for the Diabetes Prevention Program Research
N Engl J Med. 2002;346:393-403.
ADA 2013 Standards of Care. Table 4, pS14.
StudyInterventions
LifestyleIntervention
Eligible participants
Anintensiveprogramwiththefollowing
specificgoals:
Randomized
Standard lifestyle recommendations
• > 7% loss of body weight and maintenance of
weight loss
– Dietary fat goal -- <25% of calories from fat
Intensive
Lifestyle
(n = 1079)
Metformin
Placebo
(n = 1073)
(n = 1082)
– Calorie intake goal -- 1200-1800 kcal/day
• > 150 minutes per week of physical activity
DiabetesIncidenceRatesbyAge
DPP: Incidence of Diabetes
– Placebo:11%/yearincidence
– Metformin:7.8%/yearincidence*
– Lifestyleintervention:4.8%/yearincidence*
• Riskreduction:
– 31%bymetformin
Cases/100 person-yr
• Metformin,intensivelifestylemodificationdelayedor
preventedtype2diabetesvsplacebo(11%/year
incidence)
Lifestyle
Metformin
Placebo
12
8
4
– 58%bylifestyle
– 39%lifestylevsmetformin
0
25-44 (n=1000)
*P<0.001
vs placebo
Knowler WC, et al. for the Diabetes Prevention Program Research
N Engl J Med. 2002;346:393-403.
HowDoWeReplicateDPP
CDC:NationalDiabetesPreventionProgram
www.cdc.gov/diabetes/prevention/about
www.cdc.gov/diabetes/prevention/pdf/dprp_standar
ds_09022011.pdf
Nationallyrecognizeddiabetespreventionprogram
InauguralpartnersweretheYMCAandUnitedHealth
Evidencedbasedprogramusinglifestylecoaches
4pharmaciesnationallyrecognized
45-59 (n=1586)
> 60 (n=648)
Age (years)
The DPP Research Group, NEJM 346:393-403, 2002
OutcomesAssociatedwiththe
YMCADPPModel
Intervention:
- Standard curriculum
- 12 sessions
- 60-90 minutes each
- Over 8 months
Colorado:
Firstcertifiedprogramin2013
CurrentlynopharmaciesarerecognizedinCO
Ackermann RT, etal. Chronic Illness. 2011: 7(4) 279–290
WhatistheRoleofthePharmacist?
• Whatroledopharmacistshaveindietary
educationanddiseaseprevention?
ReimbursementforNationalDPP
Thirdpartyreimbursementforrecognizedsites
Reimbursementisbasedonperformanceofthe
DPP
Weightloss
Percentofvisitsattended
Reimbursementisbetterforpreventionthan
management
OtherStrategiestoImproveGlucose
Control
CostsofDiabetesMedication
Nonadherence
¾ 4050%ofpatientswithDiabetesareconsidered
nonadherent(basedonMPR<80%)
Brainstormfor12minutesaboutwhatother
interventions(excludingdietandexercise)may
improveglucosecontrolinapatientwith
diabetes
• 37%lesspharmacycosts
• 7%loweroutpatientcosts
• 41%higherinpatientcosts
Improvingmedicationadherencewouldresultin
costsavingsof$661millionto$1.16billionperyear
Egede LE, etal. Diabetes Care 35:2533–2539, 2012
ClinicalImplicationsofNonadherence
MedicationAdherence
Howdoyoucurrentlyassessmedicationnonadherence
• KPCOData
inover
11,000pts
• UsedPDC
<80%
Howdoyouknowyourpatientisadherent?
Refills
Selfreport(Morisky)
Proportionofdays
covered(PDC)
ContinuousData
Ho MP, etal., Arch Intern Me. 2006;166:1836-41
BenefitsofIncrementalChangesto
Adherence
• InitialDrugTx
• Each10%
increasein
adherence
resultedin0.1%
increase
• Otherstudies
havereported
upto0.25%
decreaseinA1c
foreach10%
improvementin
adherence
Rozenfeld Y, etal. Am J of Managed Care. 2008;14:71-75
BarrierstoMedicationAdherence
• Lackofknowledge
– Unsureofmedicationbenefits
– Concernofmedicationsafety
• Fearofhypoglycemia
– Insulin
– SU
• Costs
• Myths(many)
StrategiestoImproveMedication
Adherence
•
•
•
•
•
•
•
•
HowtoMotivatethePatient
1. Motivationalinterviewing isaperson
centered,directivemethodof
communicationforenhancingintrinsic
motivationtochangebyexploringand
resolvingambivalence
PatientEducation
AutomatedRefillSystem
Refills
MedicationDiscountPrograms
SpecialPackaging
Reminders
Technology
MotivationalInterviewing
• R =Resistingthe rightingreflex;
• U=Understandingandexploringthepatient’sown
motivations;
• L =Listeningwithempathy;
• E =Empoweringpatients,encouragingtheirhopeand
optimism.
GlucoseTestingtoImproveGlucose
Control
CostsofSMBGinUSA
• Whoshouldtesttheirbloodglucose?
• HowoftenshouldapatientwithdiabetestesttheirBG?
• Whoisresponsibleforprovidingmeaningtotheseself
monitoringofbloodglucose(SMBG)values?
• WhatistheroleofthedoctorinevaluatingSMBGvalues?
• Doesitimproveglucosecontrol?
Sam’sSimpleMath
•
•
•
•
•
26millionpeoplewithDM(T1andT2DM)
7millionundiagnosed
Assumethat10millionAmericanstestoncedaily
$0.50 $1.00perstrip
$510million/dayOR$150300million/month
$1.83.6Billionperyear
BenefitsofGlucoseTesting
DiabetesType
H1c Effects
Hypoglycemia
Type1diabetes
Possiblebeneficialeffectin
loweringHbA1c
Possiblebeneficialeffectin
identifyinghypoglycemic
events
(lowlevelevidence)
(lowlevelevidence)
Type2usinginsulin
Possiblebeneficialeffectin Possiblebeneficialeffectin
loweringHbA1c
identifying
(lowlevelevidence)
hypoglycemicevents(low
levelevidence)
Type2notusinginsulin
Noclinicallyrelevanteffect Nobeneficialeffectin
inloweringHbA1c
identifyinghypoglycemic
(highlevelevidence)
events
(moderatelevelevidence)
Cefalu WT, Diabetes Care. 2013;36:176
ADAGuidelineStatementon
SMBG
1.Whenprescribedaspartofabroadereducational
context,SMBGresultsmaybehelpfultoguide
treatmentdecisionsand/orpatientselfmanagement
forpatientsusinglessfrequentinsulininjectionsor
noninsulintherapies.(E)
2.WhenprescribingSMBG,ensurethatpatientsreceive
ongoinginstructionandregularevaluationofSMBG
techniqueandSMBGresults,aswellastheirabilityto
useSMBGdatatoadjusttherapy.(E)
ADA Standards of Care, 2013
Sam’sIdealisticSMBGGoal
FrequencyofTesting
1. Allpatientswouldtestwithapurpose
2. Testinpairsorstructuredglucosetesting
3. Allpatientswouldbeeducatedonhowto
problemsolveandmanageabnormalBGs
oridentifytrends
4. Allproviderswoulddownloadmeters
5. Allproviderswouldinterpretreports
6. Drugtherapywouldtargetglucosedefects
HowoftenshouldwetellpatientstotestBG?
(weekly,daily,twicedaily,4timesdaily7
timesdaily)
• StructuredTestingisrelativelynew
• Takesadvantageofseveraldaysofmore
intensemonitoring
• Patientstestwithapurpose
STePStudy:360ViewSMBGlog
Study:STePProgram
• PatientsenrolledtostructuredSMBGtesting
program(enhancedgroup)orusualcare
• Patientsaskedtokeeprecordsinaglucoselog
• Duration:12months
• Enhancedgrouppatientsandprovidersreceived
trainingoninterpretationofdata
Polonsky W, etal. Diabetes Care, 2011
STePStudy:360ViewSMBGlog
SMBG:StructuredvsUsualCare
Polonsky, W. Diabetes Care 2011
SMBG:StructuredvsUsualCare
adherentvsnonadherent
RoleofthePharmacist
ClinicalInertia:STePStudy
Conclusions
• 57%weightlossthroughdietandexercisereducesthe
progressiontodiabetesby58%inpatientswithpredm
• Whatistheroleofthepharmacists?
Summary:
1. SMBGisbeneficialinpatientswithtype2diabetes
(notoninsulin)ifusedappropriatelybythe
patientandprovider
2. Patientsandprovidersneedtoevaluatedata
(downloads)
3. Improvededucationaleffortsforprovidersand
patients
• Thisweightlosscannowbereimbursedthrougha
nationallyrecognizedDPP
• Medicationnonadherenceoccursin4050%ofpatients
withdiabetesandpharmacistshaveanexcellent
opportunitytoaddressthisissue
• TestingBloodglucosesinastructuredmannercangive
theproviderandpatientabetterunderstandingoftheir
diabetescontrolwhichleadstoimprovedprescribingand
overallglucosecontrol.
Summary
Pharmacistscanplayasignificantrolein
improvingdiabetesselfcarethroughimproving:
• Diet/exercise(forprediabetesanddiabetes)
• Improvingmedicationadherence
• Educatingpatientsandprovidersabout
structuredglucosetesting
2014 Regulatory and Legislative Update: State and National Perspectives
ACPE # 0008-0000-14-005-L03-P (1 contact hour – knowledge based)
Val Kalnins, RPh
Executive Director
Colorado Pharmacists Society
Learning Objectives
1. Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice
of Pharmacy.
2. Summarize the latest developments in state and national initiatives and legislation related to pharmacy.
3. Describe the impact of FDA, DEA, and state board of pharmacy rules and proposed rules of 2012-2013.
2/10/2014
Objectives
2014 Regulatory and Legislative Update:
State and National Perspectives
Val Kalnins, R.Ph
CPS Executive Director
• Discuss the latest developments concerning the Affordable Care Act and how they will affect the practice of pharmacy.
• Summarize the latest developments in state and national initiatives and legislation related to pharmacy.
• Describe the impact of FDA, DEA and state board of pharmacy rules and proposed rules of 2012‐2013.
February 22, 2014
H.R. 3200
America’s Affordable Health Choices Act
Disclosure Statement – no financial relationships to disclose
Val Kalnins has no relevant financial relationships with commercial interests pertaining to the content presented in this program.
Pharmacy Principles of HCR
Introduced 7/14/2009 by Rep. Dingell
Sets provisions governing health insurance plans and issuers
• Five different bills
•
•
–
–
3 in the House of Representatives (Tri‐Committee
2 in the Senate (HELP and Finance)
Pharmacy Principles of HCR
Principle I: Quality and Safety
•
•
•
Improve Quality and Safety of Medication Use
Assure Patient Access to Needed Medications & Pharmacy Services
Promote Pharmacy and Health Information Technology Interoperability
 Provide access to MTM services
 Provide compensation for MTM services
Principle II: Infrastructure
 Include pharmacists in workforce strategies
 Provide patient choice of MTM provider (w/in their plan)
 Provide appropriate reimbursement for dispensing‐
related services
 Ensure no artificial barriers to generic substitution
1
2/10/2014
Pharmacy Principles of HCR
Principle III: Health Information Technology
Provide pharmacists access to patient information in an electronic, interoperable, multi‐directional format
Establish and provide pharmacist access to grants
Ensure access to information, while protecting patient information
Pharmacy Principles of HCR
•
•
•
•
•
Health Care Reform – Final Bill
HR 3590
Amend the Internal Revenue Code of 1986 to modify the first‐time homebuyers credit in the case of members of the Armed Forces and certain other Federal employees
PL 111‐148
The Patient Protection and Affordable Care Act
Repeal of ACA
Unconstitutional
‐ Commerce Clause ‐ Taxing Power of Congress
• Lower Courts Decisions
• 5/4 ruling upholds almost all the ACA
•
Provide Medication Therapy Management Services Include Pharmacists as Part of Integrated Care Models Include Pharmacists in Payments for Transitional Care Activities
Conduct a MTM Pilot Include Pharmacists in Workforce Strategies
Health Care Reform – Final Bill
H.R. 4872
Health Care and Education Reconciliation Act of 2010 (Final Health Care Legislation)
PL 111‐152
Reconciliation Act
Supreme Court Ruling
• Neither “side” liked the opinion
– “Against” disagreed about the individual mandate
– “For” disagreed that the individual mandate was a tax and therefore constitutional
• What was lost: states don’t have to accept the Medicaid expansion or lose all Medicaid funding
2
2/10/2014
Repeal of ACA
The House of Representatives has voted ____ times to repeal or “dismantle” ACA
These repeal votes A. are for political “show”
B. affect public perception of ACA
C. have had major effects on ACA
D. all of the above
Web Site
October 100,000 enrolled
November 250,000 enrolled
December 975,000
Sec. Sebelius Announces 2.1 Million enrolled (12/30/13)
• 3.5 % have actually paid a premium and thereby enrolled in coverage.
• System that transmits information to insurers?
•
•
•
•
Enrollment Demographics
• Hard to Say
• Are young adults enrolling?
22% (data from 7 state exchanges)
40% hoped or expected
• “Death spiral?”
• Are insurance companies worried?
Enrollment
• As of December 31, 3013, ____ million people now have health coverage because of the Affordable Care Act
•
•
•
•
A. 3.7 B. 6.4
C. 8.1
D. 9.6
Insurance Co Protections
Three R’s
• Reinsurance
Pot of money for reimbursement • Risk Corridors
If insurers costs higher than planned,
gov’t pays excess
• Risk Adjustment
Insurance Co’s pay each other
3
2/10/2014
Like Your Plan – Keep It
• Grandfathered Plans – those that existed on March 23, 2010 are exempt from some new requirements.
• These plans can continue to "innovate and contain costs by allowing insurers and employers to make routine changes without losing grandfather status."
Like Your Plan – Keep It
• HHS Rules‐Lose Grandfather Status if:
‐ Cut or Reduce Benefits
‐ Raise Co‐Insurance Charges
‐ Significantly Raise Co‐Payment
‐ Significantly Raise Deductibles
‐ ‐ Significantly Lower Employer ‐ ‐ Add or tighten annual limit
‐ Change Insurance Companies.
Contributions
Like Your Plan – Keep It
Like Your Plan – Keep It
• How many have had their insurance cancelled? 4.7 Million
• Only affect those who buy their own insurance? 5% of population=15 Million
• Those with Employer Sponsored Insurance=156 Million
• Federal Register, page 34552 6/17/10
“the Departments’ mid‐range estimate is that 66 percent of small employer plans and 45 percent of large employer plans will relinquish their grandfather status by the end of 2013.”
What The ACA Does
ACA Shortcomings
Helps 32 Million Get Insurance
Prohibits use of preexisting conditions as a reason for denial of services Covers preventive services under Medicare.
Closes Medicare Part D “donut hole.” Covers children until age 26
Mandates coverage by 2014
Creates “Exchanges.”
• No requirements to change care delivery and payment systems to decrease costs/increase value (supports pilot programs only)
• Penalties on business too low (penalties lower than providing health insurance)
• Penalties on individuals too low
• Capacity improvements will lag demand
• Not all will be covered (34 million nation‐wide.)
•
•
•
•
•
•
•
4
2/10/2014
ACA: 2014
ACA: 2014
•
•
Mandate insurance coverage
•
Penalty of $95 or 1% of income
Penalty of $695 or 2.5% of income (2016)
Penalty applies to each adult in household
$2085 annual limit for families
Not fined if financial hardship, American Indian, religious exemption or prisoner. – Not fined if cheapest plan>8% of income
– Not fined if income too low
–
–
–
–
–
•
•
•
•
Establish Insurance Exchanges
Insurance companies can’t place lifetime or annual limits.
Denial of coverage for preexisting conditions prohibited.
Denial of coverage for health conditions, past medical problems or gender prohibited.
Insurers can charge those >65 no more than 3 x the amount charged to younger adults.
Expands Medicaid
ACA: Pharmacy Provisions
ACA: Pharmacy Provisions
• Where “Pharmacist” appears in the 2409 page document ‐ Innovations in Health Care Workforce (3021)
‐ Independence at Home Pilot(3024)
‐ Reducing wasteful dispensing of outpatient Rx drugs in LTCFs (3310)
‐ Grants or Contracts to implement Med Management Services in treatment of chronic diseases (3503)
‐ Health Care Workforce (5101 pg 1272)
‐ Geriatric Career Incentive Award (5305 ‐ Improvement in MTM Part D (10328)
• Team members for “independence at home medical practice” and “patient‐centered medical homes”
‐
5
– Access to pharmacist‐delivered medication management services including medication reconciliation
• Providers for pharmacist‐delivered medication management services under scope of practice (specifically for high risk patients)
• Medicare Part D plan sponsors must offer medication management services with annual pharmacist review
ACA: Pharmacy Provisions
• Collaborative pharmacy practice agreements as allowed by state law and scope of practice; can include:
– patient assessment
– formulating treatment plan
– selecting, initiating, modifying, recommending changes to or administering medication therapy
– patient monitoring
ACA: Pharmacy Provisions
•
Medication Therapy Management must be offered by Med D Plans to include:
‐ review of individual’s medications
‐ written or printed summary
‐ follow up interventions
‐ automatic enrollment of beneficiaries
‐ offer opt‐out option
‐ assessment, at least quarterly, of those
not enrolled in MTM program
5
2/10/2014
ACA: Pharmacy Opportunities
ACA: Pharmacy Opportunities
•
•
•
•
•
Establishes Center for Medicare and Medicaid Innovation (3021) Pilot Program for Integrated Care (2704)
Independence at Home Demonstration (3024)
Community‐Based Care Transitions Program (3026)
Community Health Team to Support the Patient Centered Medical Home (3502)
ACA: Pharmacy Opportunities
•
•
Medication Management Grant Program
Establishes National Health Care Workforce Commission
‐ definition of “health care workforce” includes pharmacists
‐ definition of “health professionals” includes
clinical pharmacists, representatives of schools of pharmacy and pharmacists
“Improving Care Transitions Optimizing Medication Reconciliation”
• Scope of practice could enhance role in patient care
• Transition of Care
• Medication Reconciliation
• Medical homes, Accountable Care Organizations and other delivery/payment system reform pilots could support an expanded role in chronic disease management and medication counseling, monitoring, etc.
• ASHP and APhA released a white paper highlighting the need for pharmacists to take leadership in implementing medication reconciliation.
• Applying a standardized approach will help cut down on medication errors ‐ when approximately half of them are attributed to communication at transitions of care. • White paper indicated a strong medication reconciliation strategy uses HIT solutions to help share important clinical information.
Med Rec and Meaningful Use
Reducing Hospital Readmissions
• Incorporating pharmacists in all stages of the medication reconciliation process remains vital for providing safe and effective patient care
• CMS recently released stage 2 criteria for meaningful use of certified electronic health records (EHR) technology
• Newly released criteria/objectives/measures: – medication reconciliation: 'Perform medication reconciliation for more than 65 percent of transitions of care in which the patient is transitioned into care..' • The Hospital Readmissions Reduction Program levels penalties against hospitals with "excessive readmissions" after risk adjustments are applied. • penalties will apply to all Medicare payments, not just those associated with excessive readmissions. • reimbursement reductions begin in 2013, with penalties determined by clinical outcomes monitored in federal fiscal 2012 (Oct 2011‐Oct 2012)
• Utilize Treatment Guidelines
6
2/10/2014
National
Legislation and Initiatives
Opportunities for Pharmacy
• Pharmacists Recognized as Health Care Providers
• Report to U.S. Surgeon General
• Patient Centered Primary Care Collaborative (PCPCC)
• Comprehensive Medication Management
• Accountable Care Organizations
FDA/DEA &
State Board of Pharmacy Rules
•
•
•
•
Return and Disposal of CS (DEA Rule)
Drug Shortages (FDA Rule)
Behind the Counter Drugs (FDA Rule)
CO Board of Pharmacy Rules
•
•
•
•
•
Compounding (Federal)
Provider Status (CA)
Improve Access to MTM Services
Better Care Programs
Reschedule Hydrocodone Combination Products
State
Legislation and Initiatives
• Colorado Coalition for Prescription Drug Abuse Prevention • Prescription Drug Monitoring Program • Medication Synchronization
• Telepharmacy
• Compounding
7
Drug Interactions Every Pharmacist Should Know
ACPE # 0008-0000-14-006-L01-P (1 contact hour – knowledge based)
Daniel Malone, RPh, PhD
Professor
College of Pharmacy
University of Arizona
Learning Objectives
1. Describe the basic mechanisms for drug-drug interactions.
2. Identify medications involved in clinically relevant interactions.
3. Given selected drug-drug interactions, determine possible management strategies to minimize or avoid
harm.
2/24/2014
DRUG-DRUG INTERACTIONS
EVERY PHARMACIST SHOULD
KNOW
Dan Malone, RPh, PhD
Professor
University of Arizona
Terminology
• Drug-drug interaction (DDI):
Clinically meaningful alteration in the effect of
one drug (object) as a result of coadministration of another (precipitant)
• Potential drug-drug interaction (PDDI):
Co-prescription or co-administration of drugs
known to interact, regardless of whether harm
ensues
DDI Prevalence in Elderly
• Elderly veterans with
new DDI at ED
discharge:1 13%
• Older adults exposed to
a “major” DDI:2 4%
• Medicare Part D
enrollees exposed to
certain DDIs: 7.3%
1) J Am Geriatr Soc. 2008;56:875-80. 2) JAMA. 2008;300:2867-78.
DISCLOSURE STATEMENT
Daniel Malone
I have no relevant financial relationships with
commercial interests pertaining to the content
presented in this program.
Drug Interaction Knowledge and
Information Sources
• Prescriber knowledge is lacking1,2
• 42.7% of drug pairs correctly identified1
• Information sources use by prescribers3
also lacking knowledge4
• Pharmacists 68.4%
• PDA 15.8%
similar to online resources
• Alerts 10.8%
• Other sources 5.1%
known to be problematic
e.g., compendia, labeling
1) Ko et al. Drug Saf. 2008;31(6):525-536. 2) Glassman. Med Care.
2002;40(12):1161-1171. 3) Ko et al. Res Social Adm Pharm. 2008;4(4):355366. 4) Weideman et al. Am J Health Syst Pharm 1999 56: 1524-1529.
Health Systems Approach to DDIs
• Evidence for DDIs is lacking
• Very few well-controlled studies
• Lack of concordance among DDI compendia1
• Differing severity rating systems, terminology,
methodologies
• Limitations of DDI clinical decision support2-4
• “Alert fatigue”
• High rates of alert override
1) Abarca et al. J Am Pharm Assoc (2003). 2004;44(2):136-141. 2) Grizzle et al. Am J Manag Care.
2007;13(10):573-578. 3) Murphy et al. Am J Health Syst Pharm. 2004;61(14):1484-1487. 4) Abarca et
al. J Manag Care Pharm. 2006;12(5):383-389.
1
2/24/2014
Improving Knowledge to Prevent
Exposure to Potential DDIs
Drug A +
Drug B
• Understanding basic concepts allows for more
Drug Interaction Defenses
Prescriber’s Knowledge
Computer Screening
rationale DDI predictions
• Prevent adverse DDIs by making patient- and
situation-specific assessments
• When appropriate:
Pharmacist’s Knowledge
Patient Risk Factors
Pharmacogenetics
Drug Administration
Patient
Education
• Avoid concomitant administration
• Implement alternative therapeutic strategies
Defenses
Monitoring
• Take precautionary measures
ADR
Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990
A+B
Pharmacokinetic Drug Interactions
“When the Holes Line Up”
Prescriber’s Knowledge
Computer Screening
Pharmacist’s Knowledge
Patient Risk Factors
Drug Administration
Patient Education
Monitoring
Defenses
ADR
Latent Failures
Hansten PD, Horn JR. Modified from: James Reason, Human Error, 1990
Drug Interaction Mechanisms
• Pharmacodynamic
•
Additive or antagonistic pharmacologic
effects
• Pharmacokinetic
Absorption
• Distribution
• Metabolism
• Excretion
•
Altered drug elimination is the most
common cause of adverse PK DDIs
• GI absorption
• Drug binding in GI tract
• Alterations in GI motility
• Alterations in GI pH
• Cytochrome P450
• Induction or inhibition
• Transport proteins
• Induction or inhibition
• Plasma protein binding
• ? clinical significance
P-glycoprotein (PGP):
an efflux transporter
Figure reproduced with permission from BioMed Central
(http://www.biomedcentral.com):
Edwards G. Filaria J. 2003;2(Suppl 1):S8.
Drug Interaction Mechanisms (continued)
Pharmacokinetic Interactions
• GI absorption
• Drug binding in GI tract
• Alterations in GI motility
• Alterations in GI pH
• Plasma protein binding
• Not clinically significant
• Cytochrome P450 (CYP)
• Induction or inhibition
• Transport proteins (P-glycoprotein [PGP])
• Induction or inhibition
2
2/24/2014
Cytochrome P450 (CYP) Enzymes
Human
CYP
CYP
Family
Subfamily
Gene
1
A
B
2
C
3
D
E
A
2
6
8
9
19
6
1
4
Clopidogrel
Tamoxifen
Macrolides, Azole
antifungals
Analysis of Arizona Medicaid Claims
16 Drug
Combinations
Identified
Prescription Claims
N = 1,723,924
• Collapse to patient level
Persons
N = 38,418
Who Prescribes Drug-Drug Interactions?
Potential Drug-Drug Interactions
by the Same Prescriber
70
60
50
40
30
20
10
0
Overall lapping days supply
Potential Drug-Drug Interactions
N = 25,553
• 67-year-old woman
• Diagnosed with pneumonia after
mitral valve repair
• Developed the following on
electrocardiogram...
Past Medical History
•Chronic atrial fibrillation
•Heart failure
•Hypertension
•Hypothyroidism
•Obesity
Medications
New medications:
•Amiodarone
•Levofloxacin
Case adapted from: Proc (Bayl Univ Med Cent). 2006;19(4):345-6.
Usually Avoid This Combination
Amiodarone-Levofloxacin
Risk Factors for TdP
• Additive risk of QTc
• Concomitant QTc-prolonging drugs
prolongation
• Potentially fatal
• Data limited regarding
arrhythmogenic risk of
drugs alone or in
combination
• Female
• Advancing age
• Cardiac disease
• Bradycardia
• Familial history long QT syndrome
• Electrolyte disturbances (e.g., low K+,
Mg++, Ca++)
QTc=rate-corrected QT interval on electrocardiogram; TdP=torsades de pointes
3
2/24/2014
Prolonged QT Risk Groups
Risk of Torsades
• Disopyramide
• Procainamide
• Quininidine
•
•
•
•
Amiodarone
Dofetilide
Ibutilide
Sotalol
• Ciprofloxacin
• Flecainide
•
•
•
•
Gemifloxacin
Levofloxacin
Moxifloxacin
Ofloxacin
• 77-year-old woman
• Presented with episodes of
• Azithromycin
• Clarithromycin
• Erythromcyin
QT drug lists by risk groups. Arizona Center for Education and Research on
Therapeutics. Available at: http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm
Warfarin-NSAID
Past Medical History
•Aortic valve replacement
•Atrial fibrillation
•Heart failure
•Hypertension
•Ischemic heart disease
Conditional Risk
of Torsades
Possible Risk of
Torsades
Usually Avoid This Combination
Case adapted from: Med J Aust. 1996;164(11):700-1.
Usually Avoid This Combination
Warfarin-NSAID (continued)
• Acetaminophen or opioids preferred
• Additive risk of bleeding
• Limit acetaminophen & monitor
• Some NSAIDs may also alter warfarin PK
• Considerable increased risk of GI bleeding1
• 13-fold higher risk hospitalization for hemorrhagic PUD
vs. neither drug; 4-fold higher risk with either drug
alone
• Co-prescribing common despite
vomiting bright red blood and
passing bloody stools
• INR 2.1 (target 2.5-3.5)
• Severe dyspnea due to aspiration
• Expired from hypotension and
multisystem failure
Medications
Chronic medications:
•Warfarin
•Furosemide
•Lisinopril
•Metoprolol
New medication:
•Ibuprofen (OTC)
risks2,3
• Most common among top 25 clinically significant
outpatient DDIs (242.7 per 1,000 warfarin recipients)
• COX-2 inhibitors
• No conclusive evidence for lower risk
• Aspirin
• Antiplatelet aspirin therapy increases minor bleeding risk
• If combined use necessary
• Monitor for bleeding
• Consider prophylaxis for NSAID-associated GI injury
1) Shorr et al. Arch Intern Med. 1993;153(14)1665-70. 2) Malone et al. J Am Pharm
Assoc (2003). 2004;44(2):142-51. 3) Malone et al. Am J Health Syst Pharm.
2005;62(19):1983-91.
Take Precautions with This Combination
Warfarin-Carbamazepine
• Carbamazepine induces warfarin metabolism
• The warfarin dose was likely previously increased
to adjust for enzyme induction
• Stopping the enzyme inducer would increase the
warfarin concentration
• The warfarin dose would be then excessive if not
adjusted
• Consider effects of stopping the precipitant drug –
generally not detected by software
Take Precautions with this Combination
Carbamazepine-Clarithromycin
• Clarithromycin inhibits carbamazepine
metabolism by CYP3A4
• Consider alternatives
• Azithromycin or non-macrolide depending on
infection and susceptibilities
• If combined use necessary, adjust and monitor
• Temporarily decrease carbamazepine dosage
(30%-50%) and monitor concentrations
• Warn patients of toxicity symptoms
4
2/24/2014
• 45-year-old postmenopausal
woman
• Underwent surgery,
chemotherapy, and radiation
therapy, followed by 6 months
tamoxifen
• Pharmacogenetic testing for
CYP2D6: extensive metabolizer
• Developed recurrence of
depressive symptoms
Past Medical History
•ER+ invasive breast
cancer
•Major depressive disorder
Medications
Chronic medications:
•Tamoxifen
Take Precautions with this Combination
Tamoxifen-Fluoxetine
• Fluoxetine inhibits conversion of prodrug
tamoxifen by CYP2D6 to its primary active
metabolite
• Concern regarding increased risk breast cancer
recurrence
• Alternative antidepressants
• Citalopram, sertraline, and venlafaxine do not
significantly inhibit CYP2D6
• Bupropion, duloxetine, and paroxetine also inhibit
CYP2D6
• Reasonable to avoid known CYP2D6 inhibitors
based on current data
Case adapted from: Am J Psychiatry. 2008;165(10):1251-5.
Past Medical History
•Hypertension
•Hyperlipidemia
Medications
Chronic medications:
•Simvastatin
•Lisinopril
•Aspirin
New medication:
•Itraconazole
• 74-year-old man
• Started treatment for toenail infection
• 3 weeks later, lower extremity pain while golfing
• Pain progressed to upper extremities and neck,
urine turned brown
• CK 22,800,000 U/L (reference range: 32-267)
Usually Avoid this Combination
Simvastatin-Itraconazole
• Itraconazole inhibits simvastatin metabolism by
CYP3A4
• Antifungal alternatives
• Consider terbinafine (not CYP3A4 inhibitor) or
ciclopirox nail lacquer (not absorbed)
• Avoid azole antifungals (inhibit CYP3A4)
• Hold simvastatin (short-term)
• NOT in unstable angina or immediately post-MI
• Statin alternatives
• Consider fluvastatin, rosuvastatin or pravastatin (not
CYP3A4 substrates)
• Avoid lovastatin and atorvastatin (to a lesser extent)
CK=creatine kinase
Case Adapted from: Ann Pharmacother. 2006;40(4):753-7.
Usually Avoid this Combination
Simvastatin-Amiodarone
Clinically Relevant Interactions
• Amiodarone inhibits simvastatin metabolism by
CYP3A4
• Statin alternatives
• Consider fluvastatin, rosuvastatin, pravastatin (not
Object
Medications
Precipitant
Medication
DDI-Specific
Hospitalization:
Odds Ratio
95% CI
DDI-Specific
Medical
Outcome:
Odds Ratio
95% CI
Total Healthcare
Cost Difference in
Follow up Period
Amiodarone and/or
Sotalol
Macrolides or
quinolones
1.13 (0.94-1.36)
1.52 (1.40-1.66)
$1923
($1348 - $2497)
Amiodarone
Macrolides
1.21 (0.60-2.46)
1.84 (1.32-2.55)
$2784
($1509 - $4059)
Amiodarone
Quinolones
1.16 (0.94-1.42)
1.57 (1.43-1.74)
$2756
($2011 - $3500)
Carbamazepine
Azole Antifungals
3.00 (1.09-8.25)
2.40 (1.57-3.67)
$785 ($382 - $1187)
Carbamazepine
Macrolides
10.00 (1.28-78.12)
2.00 (1.23-3.27)
$1181
($722 - $1640)
metabolized by CYP3A4)
• Avoid lovastatin and atorvastatin (to a lesser extent)
• If combined use necessary
• Maximum simvastatin dose: 20 mg/day
• Warn patients to report muscle pain, tenderness, or
weakness
Risk Factors for Rhabdomyolysis
• Advanced age (>65 years)
•Uncontrolled hypothyroidism
•Renal impairment
5
2/24/2014
Clinically Relevant Interactions
Object
Medication
Precipitant
Medication
DDI-Specific
Hospitalization:
Odds Ratio
95% CI
DDI-Specific
Medical
Outcome:
Odds Ratio
95% CI
Warfarin Interactions
Object
Medication
Total Healthcare
Cost Difference in
Follow up Period
Amiodarone
2.26 (1.89-2.70)
2.24 (2.02-2.48)
Warfarin
Sulfamethoxazole
3.40 (2.53-4.57)
2.87 (2.42-3.41)
Metronidazole
4.72 (3.22-6.91)
7.70 (6.03-9.83)
2.37 (1.70-3.31)
3.62 (2.90-4.53)
1.41 (1.00-1.99)
Azole Antifungals
2.00 (0.50-8.00)
1.33 (0.46-3.84)
$994 ($810 - $1177)
Lovastatin or
Simvastatin
Macrolides
-
9.00 (1.1471.04)
$872 ($781 - $962)
Warfarin
Lithium
NSAIDS
2.00 (0.37-10.92)
3.22 (1.90-5.47)
$681 ($491 - $870)
Warfarin
Warfarin
•Pharmacodynamic interaction: additive
• > 65 years old
•Patient Management:
• Hepatic impairment
• Co-administration of nitrates with
sildenafil may be appropriate under
certain conditions.
• Severe renal impairment
Drug
ACC/AHA Recommendations
for nitrate administration
sildenafil
24 hours
tadalafil
48 hours
vardenafil
24 hours (not in guideline)
$1656
($1382 - $1930)
$3252 ($2869 $3634)
$4533 ($4043 $5022)
$6130 ($5377 $6883)
1.67 (1.39-2.02)
$467 ($288 - $646)
Warfarin
Statins
1.61 (1.37-1.89)
1.83 (1.67-2.00)
$515 ($424 - $606)
Warfarin
NSAIDS
3.26 (2.49-4.26)
2.45 (2.09-2.87)
$1940
($1763 - $2117)
• Proposed mechanism of interaction:
•
•
•
•
•Predisposing factors:
Fluconazole or
Voriconazole
Fenofibrate or
Gemfibrozil
Total Healthcare
Cost Difference
in Follow up
Period
Statins and Gemfibrozil (Fibrates)
hypotensive effects
•flushing, dizziness, headache, death
DDI-Specific
Medical
Outcome:
Odds Ratio
95% CI
DDI-Specific
Hospitalization:
Odds Ratio
95% CI
Warfarin
Lovastatin or
Simvastatin
Other Interactions to Avoid
Sildenafil and Nitrates
Precipitant
Medication
Displacement of protein binding
Atypical enzyme interaction
Direct action on myocytes
Interference with multiple drug resistance protein (MDRP)
• Risk of co-administration:
Severe myopathy, Rhabdomyolysis, Acute renal failure
• Evidence:
•
PK studies and reviews of FDA Adverse Event Reporting databases
Overall incidence is rare but serious
•
•
Risk is higher for gemfibrozil than fenofibrate (15x)
Simvastatin has highest reporting rate (4/100,000)
•
• >80% of reported rhabdomyolysis cases resulted in hospitalization for renal failure
Colchicine-Clarithromycin
Summary
• Colchicine is substrate for CYP3A4 and PGP
• Clarithromycin is potent inhibitor of both
• FDA database: 60 fatalities (as of 2010)
• Retrospective case series of 88 patients
• Drug interaction knowledge is poor among
• 9 expired
• Adverse outcomes
• Pancytopenia
• GI effects: diarrhea, N/V, pain
• Myopathy
• Multi-organ failure
• Onset
• Time to symptoms – approximately 4 days
• Time to death (< 2 weeks)
health professionals
• Many DDIs result from multiple prescribers
– but not all
• Interactions can be harmful
•  Hospitalization
•  Morbidity
•  Costs
6
2/24/2014
RED Flag Medications
• Warfarin
• Macrolide antibiotics
• Clarithromycin / erythromycin
• Azole antifungals
• Anti-epileptic medications
• Amiodarone
7
Evidence-based Treatment of Hypertension and High Blood Cholesterol: Update on
New Guidelines
ACPE # 0008-0000-14-007-L01-P (1 contact hour – knowledge based)
Joseph Saseen, PharmD, FCCP, BCPS, CLS
Professor and Vice Chair
Department of Clinical Pharmacy
Professor, Department of Family Medicine
CU schools of Pharmacy and Medicine
Learning Objectives
1. Describe the process for developing new hypertension, high blood cholesterol, and assessment of
cardiovascular risk guidelines.
2. Review new guideline recommendations for the treatment of patients with hypertension and dyslipidemia.
3. List patient specific blood pressure goals and recommended treatments for patients with hypertension.
4. Identify patients who are eligible for statin-based therapy and describe how they should be treated.
2/10/2014
Evidence-Based Treatment of
Hypertension and High Blood
Cholesterol:
Update on New Guidelines
Disclosure Statement – no
financial relationships to disclose
Joseph Saseen
Statement of Disclosure
Saturday, February 22, 2014
Joseph Saseen, Pharm.D., FASHP, FCCP, BCPS
Professor and Vice Chair, Department of Clinical Pharmacy
University of Colorado Anschutz Medical Campus
I have no relevant financial relationships with
commercial interests pertaining to the content
presented in this program.
Learning Objectives
Patient Cases
• Describe the process for developing new
hypertension, high blood cholesterol, and
assessment of cardiovascular risk guidelines
• Review new guideline recommendations for the
treatment of patients with hypertension and
dyslipidemia
• List patient specific blood pressure goals and
recommended treatments for patients with
hypertension
• Identify patients who are eligible for statin-based
therapy and describe how they should be treated
50-year-old African American man has hypertension. His a
smoker. Despite lifestyle modifications for 6 months, BP is
156/96 mm Hg. TC = 205 mg/dL, HDL-C = 40 mg/dL, LDL-C =
120 mg/dL, triglycerides = 225 . No chronic medications.
70-year-old woman with hypertension, CHD (s/p MI),
dyslipidemia. Adherent with atorvastatin 20 mg daily,
carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP
is 144/90 mm Hg. No fasting lipid panel available.
60-year-old white man with hypertension and type 2
diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25
mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is
128/78 mm Hg, LDL-C is 65 mg/dL.
How should these patients be treated?
2004: NCEP ATP III Goals
Risk Category
High Risk: CHD or
CHD Equivalent
(10-y risk > 20%)
Moderately High
Risk: 2+ Risk
Factors
(10-y risk 10-20%)
Moderate Risk: 2+
Risk Factors
LDL-C
Goal
Non-HDL-C
Goal
Initiate
TLC
Consider Drug
Treatment
(mg/dL)
(mg/dL)
(mg/dL)
(mg/dL)
<100
<130
100
100
<100: for high risk patients
Optional Goal:
<70*
<100
<130
Optional Goal:
<160
130
<100
<130
<160
130
100 – 129: consider to
achieve LDL-C goal of <100
130
160
160
190
160 – 189: LDL-C Lowering
Drugs Optional
National Heart Lung and Blood Institute:
Systematic Evidence Reviews in Development
Director's Corner Message: NHLBI adopts new collaborative partnership
model for clinical practice guidelines development
Draft
Finished
Federal
Review
Expert
Review
Advisory
Council
HHS
Clearance
Partnerships
Formed
Blood
Pressure
Partner
Release
Completed
Completed
Completed
Completed
Pending
Ongoing
Cholesterol
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Obesity
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Lifestyle
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Risk
Assessment
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
(10-y risk < 10%)
Lower Risk: 0-1
Risk Factors
<160
(10-y risk < 10%)
* For Very High Risk patients
<190
NCEP ATP III =National Cholesterol Education Program.
Adult Treatment Panel III guidelines. TLC= Therapeutic Lifestyle changes
Grundy S, et al. Circulation. 2004;110:227-239.
Last Updated November 2013
http://www.nhlbi.nih.gov/guidelines/indevelop.htm#status
1
2/10/2014
Clinical Practice Guidelines for Prevention
(November 12, 2013)
2013 ACC/AHA Guidelines Focus
Three Critical Questions
• What evidence supports LDL-c goals for
secondary prevention?
• What evidence supports LDL-c goals for primary
prevention?
• What is the impact of the major cholesterol
drugs on efficacy/safety in the populations?
http://networking.americanheart.org/blogs/6/785
What is new in the 2013 ACC/AHA
Blood Cholesterol Guideline?
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ASCVD Statin Benefit Groups
Heart healthy lifestyle habits are the foundation of ASCVD prevention. In individuals not receiving cholesterol-lowering drug therapy, recalculate
estimated 10-y ASCVD risk every 4-6 y in individuals aged 40-75 y without clinical ASCVD or diabetes and with LDL–C 70-189 mg/dL.
Yes
Adults age >21 y and a
candidate for statin therapy
Yes
Clinical
ASCVD
No
The panel makes no
recommendations for or against
specific LDL-C or non-HDL-C
targets for primary or secondary
prevention of ASCVD
Yes
High
Daily dose lowers
LDL-C by approx.
≥50%
Moderate
Daily dose lowers
LDL-C by approx.
20% to <50%
Age >75 y OR if not candidate for
high-intensity statin
Moderate-intensity statin
High-intensity statin
(Moderate-intensity statin if not
candidate for high-intensity statin)
LDL-C
≥190 mg/dL
Definitions of High- and
Moderate-Intensity Statin Therapy
Age ≤75 y
High-intensity statin
(Moderate-intensity statin if not
candidate for high-intensity statin)
No
Yes
Diabetes
Type 1 or 2
Age 40-75 y
Yes
Moderate-intensity statin
Estimated 10-y ASCVD risk ≥7.5%*
High-intensity statin
No
Estimate 10-y ASCVD Risk
with Pooled Cohort Equations*
≥7.5% estimated
10-y ASCVD risk
and age 40-75 y
Yes
Moderate-to-High Intensity Statin
No
ASCVD prevention benefit of statin therapy may be less clear in other groups In selected individuals, consider additional factors influencing
ASCVD risk‡ and potential ASCVD risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
4 Statin Benefit Groups
Clinical
ASCVD
LDL-C
≥190 mg/dL
Diabetes
Type 1 or 2
Age 40-75 y
≥7.5%
estimated 10-y
ASCVD risk
and age 40-75 y
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Clinical Atherosclerotic
Cardiovascular Disease (ASCVD)
• Coronary heart disease (CHD)
– Acute Coronary Syndromes
– History of myocardial infarction
– Stable or unstable angina
– Coronary revascularization
• Symptomatic carotid artery disease
– Stroke
– TIA presumed to be of atherosclerotic origin
• Peripheral arterial disease or revascularization
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
2
2/10/2014
ACC/AHA 2013 Blood Cholesterol Guideline:
ACC/AHA 2013 Blood Cholesterol Guideline:
ASCVD
ASCVD
Class I Recommendations
Level of
Evidence
High-Intensity statin therapy should be initiated or continued as
first line therapy in men and women for < 75 years of age who
have clinical ASCVD, unless contraindicated
A
In individuals with clinical ASCVD in whom high-Intensity statin
therapy would otherwise be used, when high-intensity statin
therapy is contraindicated or when characteristics predisposing to
statin-associated adverse effects are present, moderate-intensity
statin should be used as the second option if tolerated
A
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Level of
Evidence
In individuals with clinical ASCVD >75 years of age, it is reasonable
to evaluate the potential for ASCVD risk-reduction benefit and for
adverse effects, DDIs, and to consider patient preferences, when
initiating a moderate to high-intensity statin. It is reasonable to
continue statin therapy in those who are tolerating it
B
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Statin Intensity
High-Intensity
Moderate-Intensity
Low-Intensity
Daily dose lowers
LDL–C on average,
by ~ ≥ 50%
Daily dose lowers
LDL–C on average,
by ~ 30 to <50%
Daily dose lowers
LDL–C on average,
by <30%
Atorvastatin (40)–80 mg Atorvastatin 10 (20) mg
Rosuvastatin 20 (40) mg Rosuvastatin (5) 10 mg
Simvastatin 20–40 mg
Pravastatin 40 (80) mg
Lovastatin 40 mg
Fluvastatin XL 80 mg
Fluvastatin 40 mg bid
Pitavastatin 2–4 mg
Class IIa Recommendation
Simvastatin 10 mg
Pravastatin 10–20 mg
Lovastatin 20 mg
Fluvastatin 20–40 mg
Pitavastatin 1 mg
4 Statin Benefit Groups
Clinical
ASCVD
LDL-C
≥190 mg/dL
Diabetes
Type 1 or 2
Age 40-75 y
≥7.5%
estimated 10-y
ASCVD risk
and age 40-75 y
Specific statins and doses are noted in bold that were evaluated in randomized controlled trials.
Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed
in italics.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
LDL-C ≥ 190 mg/dL
Class I Recommendations
Adults ≥21 years of age with primary LDL–C ≥190 mg/dL
should be treated with statin therapy
(10-year ASCVD risk estimation is not required):
• Use high-intensity statin therapy unless contraindicated
• For individuals unable to tolerate high-intensity statin
therapy, use the maximum tolerated statin intensity
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Level of
Evidence
B
National Lipid Association:
Familial Hypercholesterolemia
• Familial hypercholesterolemias (FH) are genetic
defects resulting in severe cholesterol elevations
and increased risk of premature CHD
• Prevalence of FH is 1 in 300 to 500
– Homozygous FH affects 1 in 1,000,000
• Aggressive lipid lowering is necessary
– Target LDL-C reduction of at least 50%
– Greater LDL-C reductions may be necessary
for FH patients with other CHD risk factors
Journal of Clinical Lipidology 2011;5:133–140.
3
2/10/2014
ACC/AHA 2013 Blood Cholesterol Guideline:
LDL-C ≥ 190 mg/dL
Class IIa Recommendation
Level of
Evidence
For individuals ≥21 years of age with an untreated primary
LDL–C ≥190 mg/dL, it is reasonable to intensify statin
therapy to achieve at least a 50% LDL–C reduction.
B
Class IIb Recommendation
C
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
LDL-C
≥190 mg/dL
Diabetes
Type 1 or 2
Age 40-75 y
≥7.5%
estimated 10-y
ASCVD risk
and age 40-75 y
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Primary Prevention in DM and
LDL-C 70-189 mg/dL
Class I Recommendation
Level of
Evidence
Moderate-Intensity statin therapy should be initiated or
continued for adults 40 to 75 years of age with DM
A
Class IIa Recommendation
Level of
Evidence
High-Intensity statin therapy is reasonable for adults age
40 to 75 years of age with DM with a 10 year ASCVD risk >
7.5% unless contraindicated
B
In adults with DM less than 40 or > 75 years of age it is
reasonable to evaluate for the potential ASCVD benefits
and for adverse effects, DDIs, and to consider patient
preference when deciding to initiate, continue, or intensify
statin therapy
C
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
2013 ACC/AHA Guideline on the
Assessment of Cardiovascular Risk
• Based on the Pooled Cohort Equations
• Predicts 10-year risk (and lifetime risk) of:
– Nonfatal/Fatal Myocardial Infarction
– Nonfatal/Fatal Stroke
• Information required:
– Age, sex, race, total cholesterol, HDL-C,
systolic blood pressure, blood pressure
lowering medication use, diabetes status,
smoking status
http://my.americanheart.org/cvriskcalculator
48-year-old African American man with type 2 diabetes. Nonsmoker. BP is 136/86 mm Hg on antihypertensive drug
therapy. TC = 200 mg/dL, HDL-C = 45 mg/dL, not on a statin.
10‐Year and Lifetime ASCVD Risks
69.0
70.0
Clinical
ASCVD
Level of
Evidence
For individuals ≥21 years of age with an untreated primary
LDL–C ≥190 mg/dL, after the maximum intensity of statin
therapy has been achieved, addition of a nonstatin drug
may be considered to further lower LDL–C. Evaluate the
potential for ASCVD risk reduction benefits, adverse effects,
drug-drug interactions, and consider patient preferences.
80.0
4 Statin Benefit Groups
4 Statin Benefit Groups
Clinical
ASCVD
LDL-C
≥190 mg/dL
Diabetes
Type 1 or 2
Age 40-75 y
≥7.5%
estimated 10-y
ASCVD risk
and age 40-75 y
Predicted Risk (%)
60.0
50.0
40.0
30.0
20.0
16.7
3.5
10.0
5.0
0.0
Your 10‐Year ASCVD 10‐Year ASCVD Risk
Risk (%)
(%) for Someone
Your Age with
Optimal Risk Factor
Levels (shown above
in column E)
http://my.americanheart.org/cvriskcalculator
Your Lifetime ASCVD Lifetime ASCVD Risk
Risk* (%)
(%) for Someone at
Age 50 with Optimal
Risk Factor Levels
(shown above in
column E)
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
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2/10/2014
ACC/AHA 2013 Blood Cholesterol Guideline:
Major CV Events at Different Levels of Risk in Primary Prevention
Baseline Risk
Categories
Events (% per year)
Statin/
Control/
more statin
Less
(n=1904)
(n=2425)
< 5%
148 (0.35%)
Risk ratio & 95% CI
229 (0.53%)
0.61 (0.45-0.81)
> 5% to < 10%
487 (1.02%)
716 (1.53%)
0.66 (0.57-0.77)
> 10% to < 20%
854 (2.52%)
1003 (2.98%)
0.82 (0.72-0.93)
> 20% to < 30%
294 (4.40%)
351 (5.28%)
0.81 (0.65-1.01)
> 30%
121 (7.29%)
126 (8.16%)
0.83 (0.58-1.18)
Subtotal
1904 (1.44%)
2425(1.84%)
0.75 (0.70-0.80)
0.6 0.8
1.0
Statin/more
statin
1.2
1.4
Control/
Less
Cholesterol Treatment Trialists Collaboration. Lancet 2012;380:581-90.
Primary Prevention no DM and
LDL-C 70-189 mg/dL
Class I Recommendations
The pooled cohort equations should be used to estimate 10 year
ASCVD risk for individuals with and LDL-C between 70 to 189
mg/dL without clinical ASCVD to guide initiation of statin therapy
for primary prevention
B
Adults age 40 to 75 years of age without clinical ASCVD or DM
and a 10 yr ASCVD risk > 7.5% should be treated with a
moderate to high intensity statin therapy
A
Class IIa Recommendations
B
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Assess medication and
lifestyle adherence
Fasting lipid panel
Primary Prevention no DM and
LDL-C 70-189 mg/dL
In adults with LDL–C <190 mg/dL who are not otherwise identified in a
statin benefit group, or for whom after quantitative risk assessment a
risk-based treatment decision is uncertain, additional factors may be
considered to inform treatment decision making. In these individuals,
statin therapy for primary prevention may be considered after
evaluating the potential for ASCVD risk reduction benefits, adverse
effects, drug-drug interactions, and discussion of patient preferences.
Level of
Evidence
Reasonable to offer moderate intensity statin to adults 40 to 75
years of age with LDL-C 70-189 mg/dL, without clinical ASCVD or
DM and a 10 year ASCVD risk of 5 to < 7.5%
ACC/AHA 2013 Blood Cholesterol Guideline:
Class IIb Recommendations
Level of
Evidence
Anticipated
therapeutic
response?
Level of
Evidence
C
• Additional Risk Factors:
– LDL-C > 160 mg/dL or genetic hyperlipidemia; Family hx ASCVD
in father < 55 yrs of age or mother < 65 years of age; hsCRP > 2
mg/dL, CAC score > 300 Agatston units or > 75 percentile for age,
sex, and ethnicity; ABI < 0.9; or lifetime risk of ASCVD
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Safety Recommendations
• Moderate-intensity statin therapy should be used
in individuals in whom high-intensity statin
therapy would otherwise be recommended when
characteristics predisposing them to statin
associated adverse effects are present
Yes
Reinforce continued adherence
Follow-up 3-12 mo
•
•
Indicators of anticipated therapeutic response and
adherence to selected statin intensity:
High-intensity statin therapy† reduces LDL–C approx.
≥50% from the untreated baseline
Moderate-intensity statin therapy reduces LDL–C approx.
30% to <50% from the untreated baseline.
No
Less-than-anticipated
therapeutic response
Yes
Anticipated
therapeutic
response?
No
Intolerance to
recommended
dose of statin
therapy
Yes
Management of
statin intolerance
No
Reinforce improved adherence
Increase statin intensity
OR
Consider addition of nonstatin drug therapy
Reinforce medication adherence
Reinforce adherence to intensive lifestyle changes
Exclude secondary causes of hypercholesterolemia
Follow-up 4-12 wk &
thereafter as indicated
Follow-up 4-12 wk
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Characteristics Predisposing
Individuals to Statin Adverse Effects
•
•
•
•
Multiple or serious comorbidities
Previous statin intolerance or muscle disorders
Unexplained ALT elevations >3 times ULN
Patient characteristics or concomitant use of
drugs affecting statin metabolism
• >75 years of age
Additional characteristics: History of hemorrhagic stroke and Asian ancestry
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
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2/10/2014
ACC/AHA 2013 Blood Cholesterol Guideline:
ACC/AHA 2013 Blood Cholesterol Guideline:
Statin Safety Recommendations
Statin Safety Recommendations
• Individuals receiving statin therapy should be
evaluated for new-onset diabetes mellitus and
those who develop diabetes mellitus during
statin therapy should engage in CV risk
reduction lifestyle modifications and continue
statin therapy to reduce their risk of ASCVD
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Lipid-Lowering Therapies
Statins
(atorvastatin, fluvastatin, lovastatin, pravastatin,
pitavastatin, rosuvastatin, simvastatin)
Bile acid sequestrants
(colesevelam, cholestyramine, colestipol)
Nicotinic acid
Fibric acid derivatives
(gemfibrozil, fenofibrate)
Cholesterol absorption
inhibitor (ezetimibe)
Omega-3 fatty acids
(Rx strength)
• Serum creatine kinase (CK) values should not
be routinely measured in individuals receiving
statin therapy
• During statin therapy, it is reasonable to
measure CK in individuals with muscle
symptoms, including pain, tenderness, stiffness,
cramping, weakness, or generalized fatigue
• Decreasing the statin dose may be considered
when 2 consecutive values of LDL–C levels are
<40 mg/dL
Nonstatin Drugs
LDL-C
HDL-C
TG
 18-63%
 5-15%
 7-30%
 15-30%
 3-5%
0 or 
 5-25%
 15-35%
 20-50%
 5-20% or 
 10-20%
 20-50%
 18%
 1%
 7%
?
 9%
 45%
The panel could find no data supporting the
routine use of nonstatin drugs combined with
statin therapy to reduce further ASCVD events
• In individuals who are candidates for statin
treatment but are completely statin intolerant, it
is reasonable to use nonstatin cholesterollowering drugs that have been shown to reduce
ASCVD events in RCTs if the ASCVD riskreduction benefits outweigh the potential for
adverse effects.
Executive summary of NCEP ATP III. JAMA. 2001; 285:2486-97; Crestor package insert. Astra-Zeneca, 2009;
Zetia package insert. Merck/Schering-Plough Pharmaceuticals, 2009; Lovaza package insert.
GlaxoSmithKline, 2009; Livalo package insert. Kowa Pharmaceuticals America, 2010.
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
ACC/AHA 2013 Blood Cholesterol Guideline:
Additional Recommendations
• The panel makes no recommendations
regarding the initiation or discontinuation of
statins in patients with NYHA Class II-IV
ischemic systolic heart failure or in patients on
maintenance hemodialysis
Parting Thoughts….
• Identified 4 statin benefit groups
• Statin intensity is clinically important
• High-priority research areas to evaluate
evidence gaps:
– Primary prevention in patients > 75 years
– Goals vs fixed-dose statin therapy
– Low-intensity statin plus nonstatin in statinintolerant patients
– New onset diabetes with statin therapy
– Role of new and emerging drug therapies
Stone NJ, et al. Circulation. 2013: published online before print November 12, 2013.
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2/10/2014
National Heart Lung and Blood Institute:
Systematic Evidence Reviews in Development
Director's Corner Message: NHLBI adopts new collaborative partnership
model for clinical practice guidelines development
Draft
Finished
Federal
Review
Expert
Review
Advisory
Council
HHS
Clearance
Partnerships
Formed
Blood
Pressure
Partner
Release
Completed
Completed
Completed
Completed
Pending
Ongoing
Cholesterol
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Obesity
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Lifestyle
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
Risk
Assessment
Completed
Completed
Completed
Completed
Pending
Ongoing
ACC/AHA
THE WRITING ON THE WALL…..
COMMENTARY
JNC 8 Transmogrified
Barry J. Matterson, MD, MBA
J Clin Hypertens 2013;10:704.
Last Updated November 2013
http://www.nhlbi.nih.gov/guidelines/indevelop.htm#status
SO WHAT CAME NEXT…..
Tuesday December 17, 2013
Clinical Practice Guidelines for the Management of
Hypertension in the Community
A Statement by the American Society of Hypertension (ASH) and the
International Society of Hypertension (ISH)
Wednesday December 18, 2014
2014 Evidence-Based Guideline for the
Management of High Blood Pressure in Adults
Report From the Panel Members Appointed to the Eighth Joint National
Committee (JNC 8)
J Hypertens 2014 Jan;32(1):3-15
JNC 8 Original Critical Questions
• Among adults with hypertension, does initiating
antihypertensive pharmacologic therapy at specific
BP thresholds improve health outcomes?
• Among adults, does treatment with an
antihypertensive pharmacological therapy to a
specified BP goal lead to improvements in health
outcomes?
• In adults with hypertension, do various
antihypertensive drugs or drug classes differ in
comparative benefits and harms on specific health
outcomes?
http://www.nhlbi.nih.gov/guidelines/cvd_adult/background.htm
JAMA. doi:10.1001/jama.2013.284427
ASH/ISH : General Recommendations
Age < 80 years:
• Goal BP is usually <140/90 mm Hg
• Past guidelines recommended <130/80 mm Hg for
diabetes, chronic kidney disease (CKD), and coronary
artery disease; however, evidence to support this lower
target in patients with these conditions is lacking
• Some experts still recommend <130/80 mm Hg if
albuminuria is present in CKD
“JNC 8” Report: General Recommendations
Age ≥ 60 years:
• initiate pharmacologic treatment at BP ≥150/90 mmHg
and treat to a goal <150/90 mm Hg
(Strong Recommendation – Grade A)
• if pharmacologic treatment results in lower achieved
SBP (e.g., <140 mm Hg) and treatment is well tolerated
and without adverse effects on health or quality of life,
treatment does not need to be adjusted.
(Expert Opinion – Grade E)
Age ≥ 80 years:
• Threshold for starting and target for treatment is ≥150/90
mmHg (if CKD or diabetes, consider <140/90 mm Hg)
Age < 60 years:
• initiate pharmacologic treatment to lower BP at ≥140/90
mmHg and treat to a goal BP<140/90 mmHg
(DBP: For ages 30-59 years, Strong Recommendation – Grade A.
DBP: For ages 18-29 years. SBP: Expert Opinion – Grade E)
J Hypertens 2014 Jan;32(1):3-15
JAMA. doi:10.1001/jama.2013.284427
7
2/10/2014
“Evidence Supporting a SBP Goal <150 mm Hg
in Patients Aged ≥60 Years: The Minority View”
ASH/ISH Guideline
Jackson T. Wright Jr., MD, PhD; Lawrence J. Fine, MD, DrPH; Daniel T. Lackland, PhD;
Gbenga Ogedegbe, MD, MPH, MS; and Cheryl R. Dennison Himmelfarb, PhD, RN, ANP
• Minority of the JNC 8 panel:
– Disagreed with increasing SBP goal from 140 to 150 mm
Hg in persons aged ≥60 yrs without DM or CKD
– Believed evidence was insufficient to justify a change
– Concerned increasing the goal may cause harm by
increasing CV risk and partially undoing the remarkable
progress in reducing CV mortality in Americans > 60 yrs
– Endorsed SBP goal <150 mm Hg in frail patients ≥80 yrs
•
SBP goal <140 mm Hg for patients <80 yrs would be in
line with guidelines from Europe, Canada, ACC-AHA,
United Kingdom, and ASH-ISH
Ann Intern Med. Published online 14 January 2014 doi:10.7326/M13-2981
ASH/ISH: Drug Therapy for
Hypertension with Other Conditions
J Hypertens 2014 Jan;32(1):3-15
“JNC 8” Report
First Drug
Diabetes Mellitus
Chronic Kidney
Disease
ACEI, or ARB
(Note: In Black patients CCB or Thiazide is acceptable)
ACEI, or ARB
(Note: In Black patients good evidence with ACEI
CAD
Beta-blocker plus ACEI or ARB
Prior Stroke
ACEI or ARB
Heart Failure
ACEI (or ARB) plus beta-blocker plus
diuretic plus spironolactone
Regardless of blood pressure if symptomatic
J Hypertens 2014 Jan;32(1):3-15
Common Themes….
JAMA. doi:10.1001/jama.2013.284427
Antihypertensive therapy
reduces risk of CV events in
patients with elevated BP!
Beta-blocker after ACEi or
ARB, CCB, and thiazide unless
coronary artery disease or
systolic heart failure is present
8
2/10/2014
Thiazide diuretics
Differences and Omissions….
Beta-blockers
Angiotensin
Receptor Blockers
Other
Antihypertensives
Calcium Channel
Blockers
ACE Inhibitors
Preferred Combinations
Possible but less well tested
Useful Combination with limitations
Not Recommended
Journal of Hypertension 2013, 31:1281–1357
KDIGO: Albuminuria Influences
Treatment
• Chronic Kidney disease, non-dialysis patients
Urine Albumin
Excretion per 24 hrs
< 30 mg
BP Goal
(mm Hg)
≤140/90
Treatment
Not specified
30 to 300 mg
≤130/80
ACE-I or ARB
> 300 mg
≤130/80
ACE-I or ARB
Recommendations & Level of Evidence
ADA: Hypertension/Blood Pressure Control
Goals
• Treat to a systolic BP goal of < 140 mmHg (B)
• Lower systolic targets (e.g., < 130 mmHg), may
be appropriate for certain patients (e.g.,
younger), if achieved without undue treatment
burden
(C)
• Treat to a diastolic BP < 80 mmHg
(B)
– Same suggestions and recommendations
provided for patients with diabetes and
without, but different cited level of evidence
Kidney International Supplements (2012) 2, 341–342
Parting Thoughts…
• General goal of <140/90 mm Hg for most
patients
• Beta-blockers are not first-line agents
• Race advocated to influence selection of drug
therapy
• Many similarities with new guidelines, but
significant yet subtle differences
Diabetes Care 2013;36 (Suppl 1): s11-s66.
Patient Cases
50-year-old African American man has hypertension. His a
smoker. Despite lifestyle modifications for 6 months, BP is
156/96 mm Hg. TC = 205 mg/dL, HDL-C = 40 mg/dL, LDL-C =
120 mg/dL, triglycerides = 225 . No chronic medications.
70-year-old woman with hypertension, CHD (s/p MI),
dyslipidemia. Adherent with atorvastatin 20 mg daily,
carvedilol 25 mg twice daily and lisinopril 40 mg daily. BP
is 144/90 mm Hg. No fasting lipid panel available.
60-year-old white man with hypertension and type 2
diabetes. Adherent with amlodipine 10 mg daily, HCTZ 25
mg daily, and ezetimibe/simvastatin 10/10 mg daily. BP is
128/78 mm Hg, LDL-C is 65 mg/dL.
How should these patients be treated?
9
2/10/2014
Challenges
"Drugs don't work in patients who
don't take them."
 Former U.S. surgeon general C. Everett Koop
http://usatoday30.usatoday.com/news/health/2007-03-28-taking-medicine_N.htm
10