Comparison of Safety and Efficacy of Direct Oral Anticoagulants plus Aspirin versus Aspirin in Coronary Artery Disease: A Meta-analysis

Background
Anti-platelet therapy has been widely used for patients with Coronary artery disease (CAD). Patients have 10% increase risk of cardiovascular events after an acute coronary syndrome within a year. Previous studies have shown decreased rates of future ischemic events in CAD with warfarin and aspirin but increased risk of bleeding. Newer studies compare the same affect with the addition of Direct oral anti-coagulation's (DOACs) to anti-platelet therapy and less risk of bleeding than warfarin. This meta-analysis investigates the efficacy and safety of to DOACs with aspirin in CAD.

Methods
PubMed, Cochran, Science Direct and Google Scholar databases were comprehensively searched through December 2018 to identify randomized clinical trials (RCTs) comparing the outcomes between DOACs plus Aspirin (Group 1) versus Aspirin alone (Group 2). The primary outcome was Major Adverse Cardiovascular Effect (MACE), and major secondary outcomes were stroke, heart failure (HF) and all-cause mortality. The safety endpoint was bleeding. Effect size of each study was computed and compared using the random-effect, Mantel- Haenszel method.

Results
Five RCTs met the inclusion criteria with a total of 47,673 patients including 23,831 (group 1) and 23,842 (group 2). There was a significant reduction in the incidence of MACE and stroke with 0.83 [0.73-0.94); p=0.004 and 0.59 [0.50-0.70]; p< 0.00001, respectively. More dose related bleeding events were reported in the group 1 compared to group 2 with 1.63 [1.28-2.07]; p< 0.0001. No significant difference was found in terms of HF and all-cause mortality between the two groups with 1.00 [0.91-1.10]; p=0.99 and 0.89 [0.77-1.03]; p=0.13.

Conclusions
The addition of DOACs to anti-platelet have shown less risk of major ischemic events in patients with CAD and the most reduction is seen in stroke when compared to aspirin alone. However, no overall mortality benefit was seen between the group. There was also increase dose dependent risk of bleeding (increase risk with 10 mg than 5 mg daily) with DOACs. This meta-analysis supports the results of recent RCT.