Are Platelet Inhibiting Prescription Drugs Used for Heart Attack Prevention Helpful?

Since aspirin can be picked up in any drug store for mere pennies a pill, the drug companies looked for something that did the same thing but that required a prescription, and that they could argue was better than aspirin or that added to aspirin. Clopidogrel (Plavix) is a pill that is promoted as complementing the effects of aspirin on inhibition of the cyclooxygenase pathway, which is said to work with aspirin by blocking platelets and therefore inhibiting blood clotting, thus preventing heart attacks. The Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) Trial randomly assigned 19185 patients with a history of recent stroke or heart attack to receive clopidogrel or aspirin for 2 years. Patients on clopidogrel had a 5.32% annual rate of a composite measure of stroke, heart attack, or vascular death, compared with 5.83% on aspirin, a difference that was barely statistically significant (CAPRIE 1996).

The CHARISMA trial involved 15,603 patients with heart disease or risk factors for heart disease who were given clopidogrel plus aspirin or aspirin alone. There was no difference between the groups in combined incidence of heart attack, stroke, or death from cardiovascular causes (Bhatt et al 2006). In the CLOpidogrel and Metoprolol Infarction Trial (COMMIT) 45852 patients with a heart attack within the past 24 hours were given clopidogrel or placebo in addition to aspirin. Clopidogrel patients had a 9% reduction in a combined measure of death, heart attack or stroke, a difference that was statistically significant (COMMIT 2006) An analysis of all of the published studies showed a 10% reduction in heart attacks and strokes in patients with a history of cardiovascular disease when clopidogrel was added to aspirin (ATC 2002). These differences, however, translate into a less than 1% reduction in absolute risk.

In the Management of ATherothrombosis with Clopidogrel in High-risk patients (MATCH) (Diener et al 2004) study 7599 patients with recent stroke or TIA with one other risk factor for heart disease were randomly assigned to receive clopidogrel or clopidogrel plus aspirin. There was no difference in rates of combined stroke, heart attack, or hospitalization between clopidogrel (17%) and clopidogrel plus aspirin (16%); a 1.3% increase in bleeding was not statistically significant. In a study of 320 patients who had developed a bleeding ulcer while taking aspirin to prevent heart disease, after the patients' ulcers healed they were randomized for a year to re-treatment with aspirin or clopidogrel. All of them also received esomeprazole. The patients who took clopidogrel had more gastrointestinal bleeding (8.6%) than aspirin patients (0.7%), a difference that is striking (Chan et al 2005).

Based on these conflicting results and the overall small benefit conferred in addition to the higher cost of clopidogrel I recommend using aspirin over clopidogrel if you have a history of heart attack or stroke. I would not consider it mandatory (or useful) to take either if you do not have a history of heart disease.

ATC (2002): Antithrombotic Trialists' Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. British Medical Journal 324: 71-86.

Bhatt D, Fox KAa, Hacke W, et al (2006): Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. New England Journal of Medicine 354: 1706-1717.

CAPRIE (1996): A randomised, blinded trial of Clopidogrel versus Aspirin in Patients At Risk of Ischaemic Events (CAPRIE). The Lancet 348: 1329-1339.

Chan FKL, Ching JYL, Hung LCT, et al (2005): Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. New England Journal of Medicine 352: 238-244.

COMMIT (2006): Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. The Lancet 366: 1607-1621.

Diener HC, Bogousslavsky J, Cimminiello C, et al (2004): Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. The Lancet 364: 331-337.