Aspirin use post-acute coronary syndromes: Intolerance, bleeding and discontinuation

Background: While aspirin's secondary prevention benefit is clear, prior reports indicate that 19-83% of eligible patients may not use aspirin chronically. Methods: We investigated intolerance and bleeding while on aspirin and aspirin discontinuation using 5337 post-acute coronary syndrome patients considered appropriate for chronic antiplatelet therapy who were randomly assigned to aspirin in SYMPHONY and 2nd SYMPHONY and followed for 94 (64,157) days. Multivariable logistic regression models tested associations between baseline characteristics and aspirin discontinuation and bleeding. Results: Nearly 18% of patients discontinued study aspirin; 48% subsequently used open-label aspirin and 5% other antiplatelet or anticoagulant therapy. Black race, recurrent ischemia, hypertension, chronic obstructive pulmonary disease, lighter weight, shorter time to treatment and use of non-steroidal anti-inflammatory agents, diuretics, and digitalis were independently associated with early discontinuation. Early discontinuation was less likely in Eastern Europe, Latin America and Asia. Although major or minor bleeding was common (12.6%), only 1.0% of aspirin-treated patients were reported to discontinue due to bleeding. Gastrointestinal (10.5%) and puncture site (7.6%) were the most common bleeding locations. Bleeding risk was associated with lower estimated creatinine clearance, shorter time to treatment, smoking, Killip class >II, higher systolic blood pressure, and use of aspirin or heparin prior to starting study aspirin. Conclusions: Despite early initiation and close followup, more than 9% of aspirin-treated patients discontinued therapy early and remained off treatment. Addressing the factors associated with both bleeding and discontinuation during chronic therapy is necessary to improve adherence to this inexpensive, life-saving therapy.