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Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS): interpretation and implementation
John Chalmers1, Stephen MacMahon
1Institute for International Health, University of Sydney, Newtown, NSW, Australia. chalmers@iih.usyd.edu.au
Insights
A perindopril-based blood pressure regimen significantly reduced stroke risk by 28% in patients with a history of stroke or transient ischaemic attack (TIA). Combination therapy with perindopril and indapamide offered greater benefits than monotherapy.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Pharmacology
Background:
- Patients with a history of stroke or transient ischaemic attack (TIA) are at high risk for recurrent vascular events.
- Effective blood pressure management is crucial for secondary prevention in these individuals.
- The role of specific antihypertensive regimens, like those based on perindopril, requires further elucidation.
Purpose of the Study:
- To evaluate the efficacy of a perindopril-based blood pressure lowering regimen in preventing recurrent stroke.
- To assess the impact of this regimen on other major vascular events and cognitive decline.
- To compare the effects in hypertensive versus non-hypertensive patients with a history of stroke or TIA.
Main Methods:
- A randomized, placebo-controlled trial involving 6105 subjects across Asia, Australasia, and Europe.
- Participants received either active treatment (perindopril-based regimen) or a placebo.
- The primary outcome was the occurrence of total stroke (fatal or non-fatal); analysis was by intention to treat.
Main Results:
- The perindopril-based regimen reduced blood pressure by 9/4 mmHg and significantly lowered the risk of total stroke by 28% (P < 0.0001).
- Major vascular events, non-fatal myocardial infarction, cognitive decline, stroke-related dementia, and disability were also reduced.
- Combination therapy with perindopril and indapamide yielded greater blood pressure and stroke risk reductions compared to perindopril monotherapy.
Conclusions:
- A perindopril-based blood pressure lowering regimen is effective in reducing stroke and other serious vascular events in patients with a history of stroke or TIA.
- The benefits were observed in both hypertensive and non-hypertensive individuals.
- Combination therapy with perindopril and indapamide should be considered for routine use in patients with a history of stroke or TIA.
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.
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