Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.
OBJECTIVE
Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials.


METHODS
Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension.


RESULTS
Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group.


CONCLUSIONS
Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.
Leonardi-Bee
Jo
J
University of Nottingham, Nottingham, UK.
Bath
Philip M W
PM
Bousser
Marie-Germaine
MG
Davalos
Antoni
A
Diener
Hans-Christoph
HC
Guiraud-Chaumeil
Bernard
B
Sivenius
Juhani
J
Yatsu
Frank
F
Dewey
Michael E
ME
D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000453:epidemiology / Q000517:prevention & control*; D004176:Dipyridamole / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
D004176:Dipyridamole; D001241:Aspirin