Abstract 1299: Primary Prevention in Diabetics: Aspirin is Insufficient
Diabetics (DM) are at increased risk for major cardiac and cerebrovascular events (MACCE) compared to non-diabetics. A prothrombotic state arising from increased platelet reactivity imparts some of this excess hazard. Primary prevention of MACCE with antiplatelet therapy in DM remains unproven in randomized trials. A systematic review of the English language literature identified 15 studies examining antiplatelet therapy for primary prevention in 10,415 diabetics with average follow-up of 5.2 years. In meta-analysis with a random effects model, there was no significant reduction in death, cardiovascular death, nonfatal MI, nonfatal stroke, or composite MACCE (Odds Ratio (OR) =0.90 (95% Confidence Interval 0.80 to 1.02) p=0.0926. However, bleeding was significantly increased, OR=3.28 (1.62 to 6.64), p=0.001 with an absolute risk increase of 0.96% (0.28 to 1.63%) p=0.0054 over 3.8 years of follow-up. Aspirin was tested in 6 studies (n=9,628), ticlopidine was tested in 5 (n=664), and cilostazol, sufinapyrazone, and dipyridamole each in 1 (n=123). Although the reduction in major cardiovascular events observed with ticlopidine did not reach statistical significance with OR=0.45 (0.17 to 1.23) p=0.112, the combined point estimate in these underpowered studies was considerably more favorable than aspirin.
Conclusion: Given the greater platelet reactivity in DM, a more potent antiplatelet agent than aspirin may be required to achieve a primary prevention benefit. With its more favorable side-effect profile and assuming future economic feasibility, clopidogrel should be prospectively tested for primary prevention in diabetics who are at acceptable bleeding risk.