Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack

Background Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease . However, there is uncertainty about the efficacy and safety of blood-pres sure-lowering treatments for many such patients. The perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the ef fects of a blood-pressure-lowering regimen in hypertensive and non-hyperten sive patients with a history of stroke or transient ischaemic attack. Methods 6105 individuals from 172 centres in Asia, Australasia, and Europe were randomly assigned active treatment (n = 3051) or placebo (n = 3054). A ctive treatment comprised a flexible regimen based on the angiotensin-conve rting-enzyme inhibitor perindopril (4 mg daily), with the addition of the d iuretic indapamide at the discretion of treating physicians. The primary ou tcome was total stroke (fatal or non-fatal). Analysis was by intention to t reat. Findings Over 4 years of follow up, active treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned active treatment suffered a s troke, compared with 420 (14%) assigned placebo (relative risk reduction 28 % [95% Cl 17-38], p < 0.0001). Active treatment also reduced the risk of to tal major vascular events (26% [16-34]). There were similar reductions in t he risk of stroke in hypertensive and non-hypertensive subgroups (all p < 0 .01). Combination therapy with perindopril plus indapamide reduced blood pr essure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy re duced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke. Interpretation This blood-pressure-lowering regimen reduced the risk of str oke among both hypertensive and nonhypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with perindopr il and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone. Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack, irrespective of their bl ood pressure.