Northern Ireland Regional Prescribing Policy on Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin – II Receptor Antagonists (A-IIRAs) Guidance on choice of ACE Inhibitors and A-IIRAs in Primary and Secondary Care This guideline on ACE inhibitors and A-IIRAs has been developed by an expert group to recommend suitable first line agents for the treatment of common therapeutic indications. The ACE inhibitors recommended by the expert group are: • Lisinopril • Perindopril • Ramipril Recommended choices for common therapeutic areas suggested by the evidence base. These represent suitable first line choices for the majority of clinical indications and are supported by clinical trial data. The A-IIRAs should be reserved for patients who are truly intolerant to ACE inhibitors in all of the therapeutic areas covered by this guidance (due to the greater evidence base and outcome data for ACE inhibitors). The A-IIRAs recommended by the expert group are: • Candesartan • Irbesartan • Losartan • Valsartan Detailed information Further information on the evidence base for these choices and additional material can be found in the accompanying support document and at: http.//www.dhsspsni.gov.uk/index/pas/pas-psip/pas-therapeutic_tendering.htm Drug Lisinopril Perindopril Ramipril Starting dose 10mg* 2mg 2.5mg Hypertension/CKD Target dose Titrate as required Titrate as required Titrate as required Candesartan Irbesartan Losartan Valsartan 8mg 150mg# 50mg# 80mg Titrate as required Titrate as required Titrate as required Titrate as required Note: Contraindications to ACE inhibitors / A-IIRAs include: • Severe valvular stenosis • Pericardial constriction • Pericardial effusion • Pregnancy Known CVD Target dose 8mg 10mg Heart Failure Target dose 30mg 10mg 32mg 160mg bd * Lower starting doses may be required in the presence of renal impairment or in patients with a strongly activated renin-angiotensin-aldosterone system. Refer to the SPC for further information. # In Chronic Kidney Disease (CKD), lower doses of irbesartan and losartan are available if appropriate. A-IIRA option If patient cannot tolerate ACE inhibitor For patients requiring therapy for 2 (or more) disease areas, select a drug recommended for both indications. Hypertension • Lisinopril or • Perindopril or • Ramipril • Candesartan or • Losartan or • Valsartan Known Cardiovascular Disease • Perindopril or • Ramipril • No major outcome data yet Heart Failure • Lisinopril or • Ramipril • Candesartan or • Valsartan Chronic Kidney Disease • Lisinopril or • Ramipril • Irbesartan* • Losartan* * evidence is in type II diabetic nephropathy or There is clear evidence in diabetic nephropathy and non-diabetic chronic renal diseases that the administration of ACE inhibitor or A-IIRA slows the progression of chronic renal failure, with the greatest benefit in patients with higher degrees of proteinuria. * Notes on initiating ACE inhibitor / A-IIRA in renal impairment can be found overleaf. Northern Ireland Regional Prescribing Policy on Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin – II Receptor Antagonists (A-IIRAs) Guidance on choice of ACE Inhibitors and A-IIRAs in Primary and Secondary Care Information on Initiating ACE Inhibitors / A-IIRAs in Primary Care The following information is a guide for General Practitioners on initiating and monitoring ACE / A-IIRAs in primary care. Before starting ACE inhibitors / A-IIRA, consider specialist advice if any of the following apply: • eGFR < 30ml/min* • Diuretic dose >80mg furosemide daily or bumetanide 2mg daily • Sodium ≤130mmol/l • Potassium >5.5mmol/l • Persistent Systolic BP <90mmHg • Known or suspected renal artery stenosis or aortic stenosis • History of angioneurotic oedema Adverse effects: Common adverse effects with ACE inhibitors and/or A-IIRAs are listed below along with advice on how these may be appropriately managed. Contra-indications to ACE inhibitor / A-IIRA therapy include: Hypotension: Cough: • Severe valvular stenosis • Pericardial effusion • Asymptomatic low blood pressure - no change in therapy required • Symptomatic low blood pressure - consider stopping or reducing other drugs. If no signs of fluid retention consider reducing diuretics • Consider other causes - respiratory disease • Exclude pulmonary oedema • If persistent and troublesome - Consider changing to an A-IIRA Renal Impairment Hyperkalaemia Declining renal function after initiating ACE inhibitor / AIIRA treatment is more likely in the elderly, patients with volume depletion (on diuretics, GI losses), severe heart failure, those on NSAIDs and those with or at risk of diffuse atherosclerosis / renal artery stenosis: For more detailed information please see the CREST Hyperkalaemia Guidelines http://www.crestni.org.uk/hyperkalaemia-booklet.pdf • Pericardial constriction • Pregnancy STEP 1 - Review current drug therapy. • Stop potassium-sparing diuretic#. • Consider reducing diuretic dose. • NSAIDs (inc. Cox-II selective) should be stopped if possible. STEP 2 - Initiate ACE inhibitor / A-IIRA & review within 2 weeks. • Start with a low dose (see overleaf). • Increase dose at weekly intervals. • Monitor eGFR, creatinine, electrolytes within 2 weeks. STEP 3 - Review after one month. • Titrate dose of ACE inhibitor / A-IIRA. • Assess any side effects & address any compliance issues. • Check need for ongoing diuretics. • Check eGFR, creatinine, electrolytes. STEP 4 - Review at 6mths & annually thereafter (or sooner if dose change or patient becomes unwell - especially dehydration). • Repeat eGFR, creatinine, electrolytes & BP as required. Maintenance. • Aim for target doses or highest tolerated dose. Remember some ACE inhibitor is better than no ACE inhibitor. • Ask about S/E - cough, dizziness etc. • Warn about drug interactions e.g. NSAIDs. * Urea levels are not included in this guidance and have been replaced by creatinine and eGFR results. # Aldosterone antagonists may be indicated concurrently with ACE inhibitor / A-IIRA treatment in congestive heart failure and should be discontinued only upon specialist advice. • An initial increase in serum creatinine (< 20%) is common and requires no action if the patient remains well and the creatinine / eGFR rise is stable. • A rise in serum creatinine concentration of ≥ 20% or fall of eGFR of > 15% during the first 2 months after initiation of ACE inhibitor / A-IIRA treatment may be an indication of underlying renal artery stenosis and need for investigation. • Increases in creatinine of between 20 - 30% (or eGFR decrease of ~15 - 20%) from baseline may be acceptable if they improve after reduction in diuretic / stopping NSAID. Reduce or stop diuretics if no signs of fluid retention. Consider reducing ACE inhibitor / AIIRA dose especially if blood pressure is at or below target. • If creatinine increases by > 30% (or eGFR decreases by > 20%) from baseline, nephrology referral is indicated and the ACE inhibitor / A-IIRA should be stopped. • Hyperkalaemia is rare in patients with normal renal function (eGFR > 60mls/min). See above. • Hyperkalaemia is classified as mild (K+ 5.5 - 6.0), moderate (K+ 6.1 - 6.9) or severe (K+ ≥ 7.0) or if ECG changes or symptoms (muscle weakness or flaccid paralysis palpitations, paresthesias) occur at ANY level or serum potassium ≥ 5.5mmol/l especially if associated with hypoxia. • K+ 5 – 6mmol/l: If this level is an unexpected or isolated finding repeat the sample without delay to avoid haemolysis causing pseudohyperkalaemia. If confirmed, this level is acceptable if the patient is well, renal function is stable and drug therapy is unchanged. • K+ 6 – 7mmol/l: Stop K+ supplements, K+ sparing diuretics and NSAIDs. Re-check within 24 hours. In the absence of these drugs stop ACE inhibitor / AIIRA. • K+ >7mmol/l: Urgent referral to hospital. NOTE: urgent treatment is required if K+ is > 7mmol/l or hyperkalaemia is accompanied by ECG changes. This summary guide is accompanied by more detailed additional notes on the evidence for selected agents and monitoring requirements. http://www.dhsspsni.gov.uk/index/pas/pas-psip/pas-therapeutic_tendering.htm