Clopidogrel Added To Aspirin During and After a Coronary Event or a Stent Procedure
Benefits in NNT
None were helped (death prevented)
1 in 27 were helped (non-fatal heart attack or stroke prevented)
96.3% saw no benefit
0% were helped by preventing death
3.7% were helped by preventing a non-fatal heart attack or stroke
Harms in NNT
1 in 114 were harmed (major bleeding event: required hospital admission and transfusion)
0.9% 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, death
Harm EndpointsBleeding, death
NarrativeAspirin blocks the action of platelets, reducing the chance of blood clots. This is proven to reduce heart attacks, strokes, and deaths among patients who have had a heart attack or stroke. Clopidogrel, another drug that blocks platelet activity, can be temporarily added to daily aspirin during times of high risk in an attempt to provide even more protection than aspirin alone. But blocking platelet activity also leads to an increased risk of bleeding events. This review examined whether temporarily adding clopidogrel to aspirin (i.e. taking both every day) is more helpful than harmful among people who have just suffered an acute coronary syndrome.
Clopidogrel added to aspirin was statistically better than aspirin alone in three large, high quality trials (roughly 8000 subjects) examining this question. There were bleeding harms caused by clopidogrel but they were less common than the benefits.
CaveatsDespite being ineffective for most patients with heart disease clopidogrel seems beneficial when added to aspirin before and after percutaeous coronary interventions (PCI) and acute coronary events. This use of clopidogrel is temporary, as both of these situations increase the risk of major events in the short-term. However, the window of benefit is narrow, because longer use has not been shown to confer any benefit, but will certainly increase the risk of bleeding. There is no evidence to suggest that any patients should therefore be taking clopidogrel for more than one year after a heart attack or PCI. In the case where clopidogrel is being used as a replacement for aspirin (rather than an add-on), it is likely that clopidogrel will have the same benefits seen with aspirin.
Technical note: To derive the NNT from the clopidogrel data we used the two highest quality systematic reviews of which we are aware. Neither pools the absolute risk data, therefore we calculated backwards from the odds ratios reported in our second source, and have estimated the overall control-event rate among the three trials to be roughly 12% (PCI-CLARITY 12%, PCI-CURE 12.6%, CREDO 11.5%). This is the control event rate for all major vascular events combined, and thus separating strokes from MIs was not possible. Therefore we report them as a combined outcome.