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-pressure-lowering treatments for many such patients. The perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive 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). Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat.

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 stroke, compared with 420 (14%) assigned placebo (relative risk reduction 28% [95% CI 17-38], p<0.0001). Active treatment also reduced the risk of total major vascular events (26% [16-34]). There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (all p<0.01). Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy reduced 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 stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with perindopril 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 blood pressure.