Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?

Table 1

Randomized clinical trials on aspirin plus dipyridamole after stroke or TIA.

Trial	Population	Antiplatelet regimen	Endpoints	Major findings
ESPS-2 [22]	6602 patients with prior (<3 months) TIA or ischemic stroke	Aspirin 25 mg twice daily or ER-dipyridamole 200 mg twice daily oraspirin 25 mg plus ER-dipyridamole 200 mg twice daily or placebo	Stroke (fatal or nonfatal), death, stroke and/or death	Significant risk reduction (37%, 𝑃<.001) in primary endpoint with combination therapy
ESPRIT [23]	2603 patients with prior (<6 months) TIA or minor ischemic stroke of arterial origin	Aspirin 30–325 mg/d plus dipyridamole 200 mg twice daily or aspirin 30–325 mg/d alone	Vascular death, nonfatal stroke, nonfatal MI, or; major bleeding compl-; ication	Significant relative risk reduction (20%, hazard ratio 0.80, 95% CI 0.66–0.98) in the primary endpoint with combination therapy
PROFESS [24]	20332 patients with prior stroke (<3 months)	Aspirin 25 mg plus ER-dipyridamole 200 mg twice daily or clopidogrel 75 mg/d alone	Stroke recurrence and composite of stroke, MI, or vascular death	The trial did not meet the pre-; defined criteria for noninferiority; . Recurrent stroke: 9.0% ER-dipyridamole plus aspirin, 8.8% clopidogrel; hazard ratio 1.01, 95%; CI 0.92–1.11. Composite endpo-; int: 13.1% ER-dipyridamole plus; aspirin, 13.1% clopidogrel; hazard ratio 0.99, 95% CI 0.92–1.07, 𝑃=.83
EARLY [25]	543 patients with ischemic stroke within 24 hours of symptomonset	Aspirin 25 mg plus ER-dipyridamole 200 mg twice daily or aspirin 100 mg/d alone for 7 days. All patients were then given aspirin plus ER-dipyridamole for up to 90 day	Functional neurological status (mRS) at 90 days; . Vascular adverse events; (nonfatal stroke, TIA, n-; onfatal MI, and major; bleeding complications) and mortality within first 90 days	No significant difference between the groups in good functional outcome (mRS 0–2; OR 1.37, 95% CI 0.86–2.18,𝑃=.19). No significant difference between the groups in composite endpoint (hazard ratio 0.73, 95% CI 0.44–1.19,𝑃=.20)

Legend: TIA: transient ischemic attack; ER: extended released; MI: myocardial infarction; CI: confidence interval.