Combined antithrombotic therapy

The study by Joseph Delaney and colleagues on the use of antithrombotic medications raises many important questions.1 In several randomized controlled trials on coronary artery disease, giving oral anticoagulants to patients whose international normalized ratio was maintained between 2 and 3 did not significantly increase the risk of major bleeding.2 When added to antiplatelet therapy, oral anticoagulation therapy leads to a marginal but statistically significant reduction of cardiovascular risk. In patients who have atrial fibrillation, deep vein thrombosis or pulmonary embolism as well as coronary artery disease, the addition of acetylsalicylic acid to oral anticoagulation therapy is important because antiplatelet therapy has very little, if any, effect on the recurrence of deep vein thrombosis and pulmonary embolism and on stroke prevention, and warfarin has a minimal effect on the recurrence of coronary events.

The combination of acetylsalicylic acid and clopidogrel in the CURE trial did not lead to excess major bleeding, although there was some minor confounding with the use of glycoprotein IIb-IIIa inhibitors.3 In support of the authors' findings, the long-term addition of clopidogrel to acetylsalicylic acid in the CHARISMA trial was not beneficial in the population as a whole and did lead to some increase in bleeding.4 In patients with acute coronary syndrome and patients who have received a stent, however, dual antiplatelet therapy is crucial and the length of therapy depends upon the clinical setting and stent type. Trial data suggest that clopidogrel therapy should be limited to patients who would most benefit from it. It does not seem prudent to change this practice on the basis of the authors' findings.

The paper by Delaney and colleagues raises the very important question of the combined use of acetylsalicylic acid with nonsteroidal anti-inflammatory drugs. There appears to limited benefit to this drug combination and it should probably be avoided.

The authors imply that warfarin, acetylsalicylic acid and clopidogrel should not be used together because of the risk of gastrointestinal bleeding. Although their findings are certainly interesting, until further work elucidates the reasons for the increased bleeding risk their data should be interpreted with caution.