Clopidogrel Added to Aspirin to Prevent a Second Heart Attack Or Stroke
Benefits in NNT
None were helped (cardiovascular problem prevented)
100% saw no benefit
Harms in NNT
1 in 167 were harmed (major bleeding event: required hospital admission and transfusion)
0.6% were harmed by developing a major bleeding event (required hospital admission and transfusion)
SourceSquizzato A, Keller T, Romualdi E, Middeldorp S. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database of Systematic Reviews 2011, Issue 1.
Bowry A, Brookhart MA, Choudhry NK. Meta-Analysis of the Efficacy and Safety of Clopidogrel Plus Aspirin as Compared to Antiplatelet Monotherapy for the Prevention of Vascular Events. American Journal of Cardiology;101(7):960-6
Efficacy EndpointsHeart attack, stroke prevention, death
Harm EndpointsBleeding, death
NarrativeAspirin blocks the action of platelets in the blood, reducing the chance of blood clots. This is proven to reduce heart attacks, strokes, and deaths among patients with known cardiovascular disease. Clopidogrel, another drug designed to block platelet activity, is often considered when patients can’t tolerate aspirin because of side effects or allergies, and there is hope that adding clopidogrel to aspirin might provide even more protection that aspirin alone. This review examined whether adding clopidogrel to aspirin (i.e. taking both every day) is helpful among people who either have cardiovascular disease already or are at very high risk for developing it.
Clopidogrel added to aspirin was not statistically better than aspirin alone in the only large, high quality trial (over 15,000 subjects) examining this question. In addition, there were bleeding harms caused by clopidogrel in this trial and many others, suggesting that the drug does not provide a measurable or proven benefit in this role, but does cause dangerous bleeding.
CaveatsThere is one other trial that compared the two drugs together to just one drug alone, but this trial compared aspirin plus clopidogrel to clopidogrel alone (rather than aspirin alone) thus we did not include these data here. However, this trial also found no benefit to combination therapy for prevention in high risk patients, but there was an increase in bleeding events.1
Note that although we have labeled this review relevant to those looking to prevent a second event, roughly 20% of the subjects in this trial had never had a heart attack or stroke, but did have multiple other very high risk features (diabetes, etc.), and were therefore considered to be at nearly equivalent risk to those who have already had a heart attack or stroke.
Finally, this is not the only use of clopidogrel. Clopidogrel does seem to provide a reliable benefit (the prevention of nonfatal heart attacks or strokes, though not the prevention of deaths) in patients having, or recovering from heart attacks and strokes, and in those undergoing 'stenting' and other procedures to open their coronary or peripheral arteries. See our relevant summaries for these data.