Table 4.

—[Sections 3.1.1-3.1.5] Clopidogrel vs Aspirin for Patients With Established CAD²⁹

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 Clopidogrel (95% CI)
Total mortalitya	19,185 (1 RCT), 1.9 y	Moderate due to imprecisionb	RR 0.98 (0.87-1.10)	120 per 1,000c	No significant difference; 2 fewer per 1,000 (from 16 fewer to 12 more)
MI nonfatal events	19,185 (1 RCT), 1.9 y	Moderate due to imprecisionb	RR 0.85 (0.72-1.00)	80 per 1,000c	12 fewer per 1,000 (from 22 fewer to 0 more)
Stroke includes nonfatal ischemic and hemorrhagic strokesd	19,185 (1 RCT), 1.9 y	Moderate due to imprecisionb	RR 0.94 (0.83-1.06)	110 per 1,000c	No significant difference; 7 fewer per 1,000 (from 19 fewer to 7 more)
Major extracranial bleede	19,185 (1 RCT), 1.9 y	Moderate due to imprecisionb	RR 0.88 (0.7-1.12)	40 per 1,000f	No significant difference; 5 fewer per 1,000 (from 12 fewer to 5 more)

See Table 1-3 legends for expansion of abbreviations.

^aOf the deaths in CAPRIE, 27 of 571 (4.7%) with aspirin were fatal bleeding events, and 23 of 560 (4.1%) with clopidogrel were fatal bleeding events.

^bRated down for imprecision due to wide CIs for absolute effects, suggesting possible harm with clopidogrel for mortality, stroke, and bleeding and possible no effect for MI. Not rated down for inconsistency, although subgroup analysis of the composite end point reported a relative risk reduction of 7.3% for patients with stroke and 23.8% for patients with peripheral arterial disease and a relative risk increase of 3.7% for patients with MI (test for interaction P = .043). Based on criteria for credibility, we did not believe the results from the subgroup analysis; therefore, we did not rate down for inconsistency.

^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 the aspirin arm of a meta-analysis of 16 RCTs in secondary prevention (Baigent et al⁹), adjusted to a 5-y time frame.

^dOf the strokes in CAPRIE, 24 of 486 (4.9%) with aspirin were hemorrhagic and 14 of 528 (2.6%) with clopidogrel were hemorrhagic.

^eOf the major extracranial bleeds in CAPRIE, 68 of 149 (45.6%) with aspirin were GI and 47 of 132 (35.6%) with clopidogrel were GI (P = .05).

^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 because these studies did not report major bleeds consistently.