ACETYL SALICYLIC ACID TARGET AUDIENCE: All Canadian health care professionals. OBJECTIVE: To provide information on the use of acetyl salicylic acid in the treatment and prevention of vascular events. ABBREVIATIONS: AAA ACS ABI ASA CABG CAD CKD ESRD HF NSAID PAD PCI PPI TIA TxA2 abdominal aortic aneurysm acute coronary syndrome ankle-brachial index acetyl salicylic acid coronary artery bypass graft coronary artery disease chronic kidney disease end stage renal disease heart failure non-steroidal anti-inflammatory drug peripheral arterial disease percutaneous coronary intervention proton pump inhibitor transient ischemic attack thromboxane A2 BACKGROUND: Acetyl salicylic acid (ASA) is well-established in the treatment of acute myocardial infarction and in the secondary prevention of cardiovascular disease among both men and women, based on large randomized trials. The net benefit of ASA use depends on weighing the anticipated reduction in cardiovascular events against the increased risk of gastrointestinal bleeding. © 2013 Thrombosis Canada. Page 1 of 5 MECHANISM OF ACTION: ASA irreversibly inhibits platelet aggregation by inhibiting thromboxane A2 (TxA2) synthesis. INDICATION: 1. Antiplatelet therapy is strongly recommended for all patients with the following, unless contraindicated: a. Cardiac: For all patients with symptomatic coronary artery disease (CAD), including: i. Acute coronary syndrome (ACS) patients with and without ST segment elevation (see STEMI or NSTEMI guides) ii. Chronic stable angina iii. Following percutaneous coronary intervention (PCI) or saphenous vein coronary artery bypass graft (CABG) b. Cerebrovascular: i. For patients with non-cardioembolic ischemic stroke or transient ischemic attack (TIA) ii. Following carotid endarterectomy c. Peripheral arterial disease (PAD): For symptomatic PAD d. Diabetes: For secondary prevention in patients with symptomatic cardiovascular disease 2. ASA should be considered in the following, unless contraindicated: a. PAD patients: i. Asymptomatic with an ankle brachial index (ABI)<0.9 at high risk because of associated atherosclerotic risk factors in the absence of risk factors for bleeding ii. Symptomatic without overt CAD or cerebrovascular disease, provided the risk of bleeding is low iii. Patients who undergo lower-extremity balloon angioplasty with or without stenting for chronic symptomatic PAD iv. For all infrainguinal reconstructions v. For all patients with abdominal aortic aneurysm (AAA) b. Primary prevention of cardiovascular morbidity and mortality: i. In special circumstances in patients without manifest vascular disease in whom vascular risk is considered high and bleeding risk is considered low ii. Patients with diabetes and aged >40 years with other cardiovascular risk factors for which ASA benefits are established and at low risk for major bleeding c. Heart Failure: i. In patients with heart failure (HF) of ischemic etiology, ASA should be dictated by underlying CAD d. Chronic Kidney Disease: © 2013 Thrombosis Canada. Page 2 of 5 i. Primary prevention of ischemic vascular events in patients with end stage renal disease (ESRD) and a low risk of bleeding ii. Secondary prevention in patients with chronic kidney disease (CKD) and manifest vascular disease for which ASA benefits are established. DOSING: a) The usual antiplatelet dose of ASA is 81 mg daily. b) A single initial dose of 325 mg is recommended in patients suffering an ACS event, and then indefinite therapy with 81 mg daily. c) An initial dose of 81 mg once daily should be utilized in patients suffering a TIA or ischemic stroke of noncardiac indication. d) For patients with a history of, or at risk of, gastrointestinal bleeding, co-administration of a gastroprotective agent should be considered (i.e. proton pump inhibitor (PPI), H2 antagonist). MONITORING: Routine laboratory monitoring is not necessary. ADVERSE EFFECTS: The most common adverse effects of ASA are bleeding into the gastrointestinal tract (which is dose-related) as well as dyspepsia. PERI-PROCEDURAL MANAGEMENT: Patients receiving ASA and: a) undergoing a diagnostic test, i. associated with a low risk of bleeding, may continue ASA without interruption. ii. associated with a high risk of bleeding, should discontinue ASA 7-10 days prior to the procedure. iii. Patients with coronary stents deserve special consideration, and consultation with a specialist is advised. b) undergoing arthrocentesis, may continue ASA through the time of the procedure. c) undergoing a minor dental, eye or skin procedure or surgery, may continue ASA around the time of the procedure. d) undergoing elective non-cardiac surgery should discontinue ASA 7-10 days prior to surgery if the risk for cardiovascular events is low, but continue if cardiovascular risk is high. © 2013 Thrombosis Canada. Page 3 of 5 SPECIAL CONSIDERATIONS: a) In patients at low risk of vascular occlusion (e.g. < 1%/yr), the small reduction of vascular events is likely offset by bleeding complications. In those at high risk of vascular events (e.g. > 3%/yr), the absolute benefit of ASA outweighs the harm. b) Patients taking ASA for vascular protection should avoid the concomitant use of NSAIDs. c) If a patient taking low-dose ASA for vascular protection requires an anti-inflammatory agent, specific cyclooxygenase-2 inhibitors should be chosen over traditional NSAIDs. d) ASA should be used with caution in patients with asthma or nasal polyps; in those at high risk of bleeding or with recent major bleeding; or in patients with thrombocytopenia or with familial or acquired bleeding disorders. PEDIATRICS: ASA may be used in infants and children with congenital or acquired heart disease or with arterial ischemic stroke. When ASA is used for antiplatelet therapy in children, it is used in doses of 1-5 mg/kg per day. ASA should be held 1 week pre- and 6 weeks post-varicella immunization. ASA is contraindicated with FluMist; therefore, Agriflu should be used instead. In general, depending on the underlying etiology of the illness, a subspecialist should be consulted prior to the use of ASA in children. REFERENCES: Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86. Antithrombotic Trialists' (ATT) Collaboration; Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009;373:1849-1860. Bell AD, Roussin A, Cartier R, et al. The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society Guidelines. Can J Cardiol 2011;27(Suppl A):S1-S59. Eikelboom JW, Hirsh J, Spencer FA, et al. Antiplatelet Drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e89S-119S. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e737S-801S. © 2013 Thrombosis Canada. Page 4 of 5 Please note that the information contained herein is not to be interpreted as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter, you should consult your doctor or other professional healthcare providers, and as such you should never delay seeking medical advice, disregard medical advice or discontinue medical treatment because of the information contained herein. © 2013 Thrombosis Canada. Page 5 of 5