Table 22.

—[Section 4.1.1] Summary of Findings: Anticoagulation Compared With Antiplatelet Therapy for Secondary Prevention in Patients With a History of Noncardioembolic Ischemic Stroke or TIAⁿ,¹⁰⁹

Outcomes	No. of Participants (Studies) Follow-up	Quality of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects, Time Frame 2 y
				Risk With Antiplatelet	Risk Difference With Oral Anticoagulation (95% CI)
Overall mortality	5,400 (5 studiesa) 0-5 y	Moderateb-e due to inconsistency	RR, 1.36 (1.09-1.7)	50 deaths per 1,000f	18 more deaths per 1,000 (from 5 more to 35 more)g
Nonfatal recurrent stroke (ischemic and hemorrhagic)	5,400 (5 studiesa) 0-5 y	Highb,d	RR, 1.03 (0.88-1.22)	106 strokes per 1,000f	3 more strokes per 1,000 (from 13 fewer to 23 more)
Nonfatal MI	1,637 (2 studiesa) 3-5 y	Moderatei-k due to imprecision	RR, 0.91 (0.59-1.4)	13 MIs per 1,000f	1 fewer MIs per 1,000 (from 5 fewer to 5 more)
Nonfatal major extracranial hemorrhage	3,194 (4 studiesl) 0-5 y	Highb,d,m	RR, 3.60 (2.29-5.66)	10 bleeding events per 1,000f	26 more bleeding events per 1,000 (from 13 more to 47 more)

See Table 1, 2, 15, and 17 legends for expansion of abbreviations.

^aGarde (1983), SPIRIT (1997), WASID (2000), WARSS (2001), and ESPRIT (2007).

^bOf the five studies, allocation was concealed in four (unclear in Garde 1983), outcome adjudicators were blinded in four (not blinded in Garde 1983), analysis was ITT in four (unclear in Garde 1983), and follow-up ranged from 97% to 100%.

^cI²=62%.

^dINR target range was 2-3 in two studies (WASID, ESPRIT), 1.4-2.8 in one study (WARSS), 3-4.5 in one study (SPIRIT). Thrombin time was 7%-15% in one study (Garde). We did not downgrade for indirectness.

^eCI includes both values suggesting anticoagulation is harmful and values suggesting anticoagulation is no different from antiplatelets. The quality of evidence could be considered as moderate if considering mortality as either unchanged or worsened with anticoagulation given a lower CI of 0.98.

^fBaseline event rates based on aspirin arm of the CAPRIE trial and adjusted for 2-y time frame.

^gAspirin (≥75 mg/d) reduces cancer-related mortality (HR=0.8) with long-term use (>5 y). Cancer-related mortality was not listed separately as an outcome because survival of stroke patients is relatively short (median survival, 5 y) and because cancer-related mortality is captured by overall mortality.

^hWASID (2000) and ESPRIT (2007).

ⁱOf the two studies (WASID, ESPRIT), allocation was concealed in both, outcome adjudicators were blinded in both, analysis was ITT in both, and follow-up ranged from 97% to 98%.

^jINR target range was 2-3 in both studies (WASID, ESPRIT).

^kCI includes both values suggesting harm and benefit.

^lGarde (1983), SPIRIT (1997), WASID (2000), and ESPRIT (2007).

^mAlthough I²=80%, we did not downgrade for inconsistency as all point estimates suggest increased major bleeding.

ⁿThe antiplatelet used in all studies was aspirin.