Table 10.

—[Sections 3.2.6-3.2.7] Triple Therapy (Warfarin, Aspirin, Clopidogrel) vs Dual Antiplatelet Therapy in Patients With Acute Large Anterior MI at Risk for or With LV Thrombus Who Undergo PCI With Stent Placement⁴⁴

Outcomes	Participants (Studies), Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects Over 3 mo
				Risk With Clopidogrel and Aspirin	Risk Difference With Warfarin + Clopidogrel and Aspirin (95% CI)
Total mortality	10,883 (10 RCT), 3-60 mo	Low due to indirectnessa and imprecisionb	RR 1.00 (0.82-1.22)	25 per 1,000c	No significant difference; 0 fewer per 1,000 (from 4 fewer to 6 more)
MI nonfatal events	10,883 (10 RCTs), 3-60 mo	Low due to serious indirectnessa	RR 0.69 (0.54-0.88)	35 per 1,000c	11 fewer per 1,000 (from 16 fewer to 4 fewer)
Stroke includes nonfatal ischemic and hemorrhagic strokesd	6,709 (1 RCT), 1.3 y	Low due to indirectnessd and imprecisionb	RR 0.56 (0.39-0.82)	Anteroapical MI without LV thrombus
				15 per 1,000e	7 fewer per 1,000 (from 9 fewer to 3 fewer)
				Anteroapical MI with LV thrombus
				100 per 1,000e	44 fewer per 1,000 (from 18 fewer to 61 fewer)
Major extracranial bleed	10,883 (10 RCTs), 3-60 mo	Low due to indirectnessa	RR 2.37 (1.62-3.47)	11 per 1,000c	15 more per 1,000 (from 7 more to 27 more)
Burden of treatmentf	Not applicable	High	Warfarin > aspirin	Warfarin: daily medication, dietary and activity restrictions, frequent blood testing/monitoring, increased hospital/clinic visits
				Aspirin: daily medication only

ACTIVE-W = Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events. See Table 1-3, and 8 legends for expansion of other abbreviations.

^aRelative risk for warfarin, aspirin, and clopidogrel vs dual antiplatelet therapy was derived from a meta-analysis of studies comparing warfarin plus aspirin to aspirin alone in patients following ACS.

^bRated down for imprecision for total mortality due to wide CIs suggesting important harm and benefit with warfarin plus aspirin. For stroke, we rated down for imprecise baseline risk estimates.

^cControl group risk estimates (aspirin + clopidogrel) come from PLATO trial, adjusted to a 3-mo time frame assuming that one-half of the total events at 1 y occurred in the first 3 mo (as was the case in the PLATO trial).

^dWe assumed that the relative risk for the outcome of nonfatal stroke (ischemic and hemorrhagic) would be the same as observed in the ACTIVE-W study, which compared warfarin to dual antiplatelet therapy (aspirin + clopidogrel). We calculated the RR and 95% CI after extracting the number of nonfatal strokes (ischemic and hemorrhagic) in each group from the published report because it did not directly report RR in the article.

^eControl group risk estimates for nonfatal stroke is based on an ∼1.5% rate/3 mo (see text) with clopidogrel and aspirin following anterior MI and 10% rate/3 mo in patients with anterior MI and LV thrombus. There is considerable imprecision in these estimates.

^fThere are studies evaluating quality of life in patients during warfarin treatment (with disparate findings), but these are limited by small sample size, lack of comparator, and other design issues.