Perindopril Protection against Recurrent Stroke Study - PROGRESS
The goal of the trial was to determine the efficacy of a flexible blood-pressure-lowering regimen, involving an ACE inhibitor (perindopril) and a diuretic (indapamide), on the risk of stroke and other major vascular events among individuals with a history of stroke or transient ischemic attack.
Patients Screened: 7,121
Patients Enrolled: 6,105
Mean Follow Up: 4 years
Mean Patient Age: mean age 64 years
History of stroke or TIA within the previous 5 years; no definite indication (such as heart failure) for treatment with an ACE inhibitor and no definite contraindication to such treatment.
Fatal or non-fatal stroke
Fatal or disabling stroke; composite of non-fatal stroke, non-fatal MI, or death due to any vascular cause (including unexplained sudden death); total and cause-specific deaths; and hospital admissions.
Eligible patients entered a 4-week pre-randomization run-in period where they received open-label perindopril (2 mg/d for 2 weeks, followed by 4 mg/d for another 2 weeks). Patients were randomized in a double blind fashion to placebo (n=3054) or the ACE perindopril (4 mg/day)(n=3051) with the addition of the diuretic indapamide at the discretion of the treating physician.
Combination therapy (perindopril+indapamide or double placebo) was used in 58% of patients in both arms, with single treatment (perindopril or placebo) used in 42% of patients in both arms. Blood pressure was reduced 9/4 mm Hg in the perindopril arm compared with placebo, and differences were maintained through follow-up. Stroke was less frequent in the treatment arm (10%, n=307) compared with the placebo arm (14%, n=420, p<0.0001). Fatal or disabling and severe strokes occurred less frequently in the active arm than placebo arm (p<0.05 for each). Risk of total major vascular events was reduced in the active treatment arm vs placebo (15%, n=458 vs 20%, n=604, p<0.05). There was no difference in all-cause mortality (10%, n=306 vs 10%, n=319, p=NS) or vascular deaths (6%, n=181 vs 6%, n=198, p=NS). Similar reductions in stroke occurred in hypertensive and non-hypertensive subgroups (p<0.01). Blood pressure was reduced by a mean of 12/5 mm Hg in patients treated with combination therapy (perindopril + indapamide) and the risk of stroke was reduced compared with patients who received double placebo (8%, n=150 vs 14%, n=255). However, among patients who received perindopril alone, there was no significant difference in blood pressure reduction (reduced by a mean of 5/3 mm Hg) or the risk of stroke (12%, n=157 vs 13%, n=165, p=NS).
Among patients with a history of stroke or TIA, treatment with the ACE inhibitor perindopril with or without the diuretic indapamide was associated with a reduction in the primary endpoint of fatal or non-fatal stroke. There was also a reduction in the secondary endpoint of any vascular event, but no significant benefit occurred in mortality. Single treatment with perindopril without indapamide showed little benefit over placebo, with most of the benefit occurring in patients treated with both perindopril and the diuretic indapamide. Because the trial was not a factorial design, it cannot be definitively ascertained whether the benefit was due to perindopril or indapamide, or if only the combination of the two provides the benefit.
Lancet 2001; 358: 1033–41.
Keywords: Perindopril, Drug Combinations, Stroke, Follow-Up Studies, Ischemic Attack, Transient, Diuretics, Heart Failure, Indapamide, Hypertension
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