No abstract

Background and Purpose-The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) showed that blood pressure lowering reduced stroke risk in patients with a history of cerebrovascular events. Here, we report the consistency of treatment effects across different stroke subtypes and among major clinical subgroups. Methods-PROGRESS was a randomized, double-blind trial among 6105 people with a prior history of cerebrovascular events. Participants were assigned to active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). Results-During a mean of 3.9 years of follow-up, active treatment reduced the absolute rates of ischemic stroke from 10% to 8% (relative risk reduction [RRR], 24%; 95% confidence interval [CI], 10 to 35) and the absolute rates of intracerebral hemorrhage from 2% to 1% (RRR, 50%; 95% CI, 26 to 67). The relative risk of any stroke during follow-up was reduced by 26% (95% CI, 12 to 38) among patients whose baseline cerebrovascular event was an ischemic stroke and by 49% (95% CI, 18 to 68) among those whose baseline event was an intracerebral hemorrhage. There was no evidence that treatment effects were modified by other drug therapies (antiplatelet or other antihypertensive agents), residual neurological signs, atrial fibrillation, or the time since the last cerebrovascular event. Conclusions-Beneficial effects of a perindopril-based treatment regimen were observed for all stroke types and all major clinical subgroups studied. These data suggest that effective blood pressure-lowering therapy should be routinely considered for all patients with a history of cerebrovascular events.

Background and Purpose-Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin D-dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Methods-Nested case-control study of ischemic (nϭ472) and hemorrhagic (nϭ83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. Results-Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and D-dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance. here is increasing evidence that hemostatic and inflammatory variables are associated with cardiovascular events in prospective studies, including coronary heart disease (CHD) and stroke. 1 Most data are available for fibrinogen, which may play a causal role in atherothrombotic events through effects on atherogenesis, thrombogenesis, or ischemia distal to atherothrombotic stenoses or occlusions. [1][2][3][4] Several prospective studies have reported that fibrinogen is associated with risk of stroke, 5-9 although not the Caerphilly and Speedwell studies. 10 Plasma fibrinogen is an important determinant of plasma and blood viscosity, which have also been reported to be associated with the risk of CHD, 11-15 although reports for stroke have been conflicting. 10,13 In part, the possible association between viscosity and stroke may be mediated by an association between viscosity and elevated carotid intima-media thickness, at least in men. 16 Ernst et al 17 observed that fibrinogen, plasma viscosity, blood viscosity, and cholesterol were associated with risk of recurrence over 2 years in 523 survivors of first stroke. Similar findings have been reported for recurrent myocardial infarction. 18 There are fewer published data on the association of other hemostatic or inflammatory variables with risk of CHD and stroke. 1 Recent meta-analyses have shown that C-reactiv...