Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS): Interpretation and implementation

Objectives: To determine the effects of a perindopril-based blood pressure lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack (TIA). Design and methods: 6105 subjects from 172 centres in Asia, Australasia, and Europe were randomised to receive active treatment (n = 3051) or placebo (n = 3054). Active treatment consisted of 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. Results: Active treatment reduced blood pressure by 9/4 mmHg over 4 years of follow-up. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo [relative risk reduction 28% (95% confidence interval 17-38), P < 0.0001]. Active treatment also reduced the risks of total major vascular events [26% (16-34)] including non-fatal myocardial infarction [38% (14-55)], severe cognitive decline [19% (4-32)], stroke-related dementia [34% (3-55)] and disability [18% (8-28)]. There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (P < 0.01). Combination therapy with perindopril plus indapamide lowered blood pressure by 12/5 mmHg and stroke risk by 43%. Single-drug therapy lowered blood pressure by 5/3 mmHg and produced no significant fall in the risk of stroke. Conclusions: The blood-pressure lowering regimen used in Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) reduced the risks of stroke and other serious events in hypertensive and non-hypertensive subjects with a history of stroke (whatever the subtype) or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger stroke reductions than monotherapy with perindopril alone. Treatment with these two agents should be considered routinely for all patients with a history of previous stroke or TIA, whether hypertensive or normotensive.