Table 5.

—[Secions 3.1.1-3.1.5] Aspirin Plus Clopidogrel vs Aspirin in the Secondary Prevention of Cardiovascular Events³

Outcomes	Participants (Studies), Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects Over 5 y
				Risk With Aspirin	Risk Difference With Aspirin + Clopidogrel (95% CI)
Total mortalitya	15,603 (1 RCT), 28 mo	Moderate due to imprecisionb	RR 0.99 (0.86-1.14)	120 per 1,000c	No significant difference; 1 fewer per 1,000 (from 17 fewer to 17 more)
MI nonfatal events	15,603 (1 RCT), 28 mo	Moderate due to imprecisionb	RR 0.94 (0.75-1.18)	80 per 1,000c	No significant difference; 5 fewer per 1,000 (from 20 fewer to 14 more)
Stroke includes nonfatal ischemic and hemorrhagic strokesd	15,603 (1 RCT), 28 mo	Moderate due to imprecisionb	RR 0.81 (0.64-1.02)	110 per 1,000c	No significant difference; 21 fewer per 1,000 (from 40 fewer to 2 more)
Major extracranial bleede	15,603 (1 RCT), 28 mo	Moderate due to imprecisionb	RR 1.25 (0.97-1.61)	40 per 1,000f	No significant difference; 10 more per 1,000 (from 1 fewer to 24 more)

See Table 1-3 legends for expansion of abbreviations.

^aOf the deaths in the CHARISMA trial, 17 of 571 (3%) with aspirin were fatal bleeding events, and 26 of 574 (4.5%) with clopidogrel and aspirin were fatal bleeding events.

^bRated down for imprecision because of wide CIs for absolute effects, suggesting important benefit, no benefit, or important harm with clopidogrel for all outcomes. Not rated down for inconsistency, although subgroup analysis found no significant effect of clopidogrel on vascular mortality in patients with established cardiovascular disease in contrast with increased mortality in asymptomatic patients. We judged claim of subgroup effect to be not credible (high number of subgroup hypotheses tested, unclear whether appropriate test for interaction used).

^cControl group risk estimates for total mortality come from the aspirin arm of the CHARISMA trial. Estimates for MI and stroke come from observed events in a meta-analysis of 16 RCTs in secondary prevention (Baigent et al⁹), adjusted to a 5-y time frame.

^dOf the strokes in CHARISMA, 27 of 189 (14%) with aspirin were intracranial hemorrhages, and 26 of 150 (17%) with clopidogrel were intracranial hemorrhages.

^eWe excluded fatal bleeding and intracranial hemorrhage to avoid the double counting of events in the CHARISMA trial. Proportion of severe GI bleeds in CHARISMA was 0.65% (not reported separately for each treatment arm).

^fControl group risk estimates come from observed major bleeding events in the CAPRIE trial, adjusted to a 5-y time frame, and not from the 16 studies included in the meta-analysis or from CHARISMA because these studies did not report major bleeds consistently.