Antiplatelet drugs in the secondary prevention after stroke: differential efficacy in large versus small vessel disease? A subgroup analysis from ESPS-2.
OBJECTIVE
Arterial disease resulting in cerebral ischemia can be classified into large vessel disease (LVD) and small vessel disease (SVD). We assessed whether antiplatelet drugs were more efficacious in large than in small vessel cerebrovascular disease.


METHODS
Individual patient data of the second European Stroke Prevention Study (n=6602), in which patients with a previous transient ischemic attack or ischemic stroke were randomized to aspirin, dipyridamole, their combination, or placebo, were reanalyzed. Type of vessel disease was classified according to clinical symptoms or physical examination. Presence of a lacunar syndrome was considered typical for SVD and evidence of cortical dysfunction for LVD. Vascular events (nonfatal stroke, nonfatal myocardial infarction, nonfatal other vascular event, or vascular death) were taken as outcome. Cox regression analyses were performed.


RESULTS
A total of 419 first vascular events occurred in 2600 patients with SVD and 367 in 1816 patients with LVD (mean follow-up 1.7 years). For aspirin versus placebo, the hazard ratio (HR) was 0.86 (95% CI, 0.66 to 1.11) in patients with SVD and 0.80 (95% CI, 0.61 to 1.06) in those with LVD (Pinteraction=0.74). For dipyridamole versus placebo, the HR was 0.86 (95% CI, 0.67 to 1.12) in patients with SVD and 0.90 (95% CI, 0.68 to 1.19) in patients with LVD (Pinteraction=0.84). Similar observations were made for the outcome stroke only.


CONCLUSIONS
Our findings do not concur with the hypothesis that aspirin, dipyridamole, or the combination may be especially effective in preventing vascular events in patients with previous cerebral ischemia that was caused by LVD compared with SVD.
Ariesen
Marie-José
MJ
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
Algra
Ale
A
Kappelle
L Jaap
LJ
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000473:pathology; D004176:Dipyridamole / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome
D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D001241:Aspirin