Preventing stroke: the PRoFESS, ONTARGET, and TRANSCEND trial programs

Abstract

Renin-angiotensin system blockers have been shown to reduce stroke risk, partly independent of their blood pressure-lowering effect. The PReventiOn regimen For Effectively avoiding Second Strokes (PRoFESS) trial, ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized AssessmeNt Study in aCE-iNtolerant subjects with cardiovascular Disease (TRANSCEND) recently showed potential benefits of the angiotensin II receptor blocker, telmisartan, in reducing secondary strokes. In PRoFESS, 20 332 ischemic stroke patients were randomized to telmisartan 80 mg versus placebo and to two antiplatelets in a 2 x 2 factorial design. After a mean exposure of 2 years, telmisartan showed a nonsignificant lower rate of recurrent stroke versus placebo [880 versus 934; hazard ratio 0.95; 95% confidence interval (CI) 0.86-1.04]. In a post-hoc analysis, from 6 months, telmisartan significantly reduced the number of strokes versus placebo (533 versus 608; hazard ratio 0.88; 95% CI 0.78-0.99; P = 0.042). In the stroke subgroup of ONTARGET, telmisartan 80 mg showed a trend toward reducing recurrent stroke versus ramipril 10 mg (hazard ratio 0.91; 95% CI 0.79-1.05). In the TRANSCEND study, 5926 patients who were intolerant to angiotensin-converting enzyme inhibitors were treated with 80 mg telmisartan or placebo. In a combined analysis of PRoFESS and TRANSCEND, the incidence of the composite of stroke, myocardial infarction, or vascular death was 12.8% for telmisartan versus 13.8% for placebo (hazard ratio 0.91; 95% CI 0.85-0.98; P = 0.013).