Should High-Risk Patients with Chronic Atrial Fibrillation and Those with Coronary Artery Disease Receive Combined Aspirin-Oral Anticoagulant Therapy or Oral Anticoagulant Therapy Alone? A Systematic Review and Meta-Analysis.

Background: Deciding between combined aspirin and oral anticoagulant (OAC) therapy compared to OAC therapy alone in patients with chronic atrial fibrillation who also have coronary artery disease or are at high risk for stroke is a common clinical problem. Individual trials do not address the benefits and risks of these two treatment strategies.

Purpose: To perform a systematic review and meta-analysis of randomized controlled trials comparing combined aspirin-OAC therapy and OAC alone with respect to bleeding complications and overall mortality.

Data Sources: Randomized trials published up to December 2004 in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases.

Study Selection: Included studies satisfied the following criteria: randomized trial involving patients, age ≥18 years, with chronic atrial fibrillation, a mechanical heart valve or coronary artery disease that compared treatment with OAC and aspirin to treatment with OAC alone; OAC therapy was the same in all treatment arms; patient follow-up for at least 3 months; the study documented at least 2 of 3 study outcomes.

Data Extraction: Two reviewers independently extracted data on thromboembolic, major bleeding and mortality outcomes. Authors were contacted if the required information was not available.

Data Synthesis: Fifteen studies were included, totalling 8984 patients with a mechanical heart valve, chronic atrial fibrillation or coronary artery disease. The risk for thromboembolic outcomes was significantly lower in patients receiving aspirin-OAC therapy compared to OAC therapy alone (OR = 0.62; 95% CI: 0.51, 0.77; P <0.001). In patients receiving aspirin-OAC therapy or OAC therapy alone, there was no difference in the risk for major bleeding (OR = 1.14; 95% CI: 0.90, 1.45; P = 0.27), intracranial bleeding (OR = 0.84; 95% CI: 0.51, 1.39), or fatal bleeding (OR = 1.36; 95% CI: 0.71, 2.61). There was no significant difference in all-cause mortality in patients receiving aspirin-OAC therapy compared to OAC therapy alone (OR = 0.93; 95% CI: 0.78, 1.10; P = 0.38). In patients receiving aspirin-OAC therapy compared to OAC therapy alone, there was no significant difference in the case-fatality rate for thromboembolism (12.1% vs. 12.2%; P = 0.99), or major bleeding (13.2% vs. 11.5%; P = 0.66).

Conclusions: Aspirin may be added to OAC in patients at high risk of thromboembolic complications since it appears to be effective with a similar bleeding risk as therapy with OAC alone. However, does not appear to reduce the risk of death.