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Dual Therapy Reduces Blood Pressure And Stroke Risk

A combination of the angiotensin-converting-enzyme inhibitor perindopril and the diuretic indapamide can substantially reduce the risk of recurrent stroke.

Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone, according to the findings of a multinational trial in Europe, Australia and Asia by clinicians with the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) study.

Clinicians taking part in the study, led by Dr. Stephen MacMahon, Institute for International Health, University of Sydney, Australia, write, "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."

They point out that stroke kills some five million people each year, making cerebrovascular disease the second leading cause of death worldwide. At least 15 million others have non-fatal strokes annually, and about a third are disabled as a consequence.

Among survivors of stroke or a transient ischaemic attack, the risk of further stroke is very high: at least one in six have another stroke within five years. "The identification of safe and effective treatments for the prevention of recurrent stroke is therefore a priority," they add.

Overall, 6,105 patients from 172 centers were randomly assigned either active treatment (3,051 patients) or placebo (3,054 patients). 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).

Clinicians found that blood pressure was lowered (by 9/4 mm Hg) and the incidence of stroke was lower in patients given perindopril/ indapamide (14 percent) than patients given placebo (10 percent) at four-year follow-up. There were similar reductions in the risk of stroke in patients given active treatment irrespective of whether they had high or normal blood pressure.

Patients given combination therapy had their blood pressure reduced by 12/5 mm Hg and stroke risk reduced by 43 percent. Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernible reductions in the risk of stroke or of major vascular events.

"Given that the study treatment was shown to be safe and effective across a broad range of patients, irrespective of blood pressure, type of qualifying cerebrovascular event, time since last event, or geographic region, the results should have implications for the care of a large proportion of all patients who survive stroke or transient ischaemic attack, Dr. MacMahon and colleagues conclude."

"For patients presenting with an acute stroke or transient ischaemic attack, the responsible physician should consider starting treatment at the time of discharge from hospital or at a post-discharge follow-up visit. For others who have had a stroke or transient ischaemic attack in the past, the general practitioner should consider starting treatment at the patient's next visit to the surgery.

"Although treatment may commence with a single agent, as it did during the run-in phase of this study, the objective should be to move patients onto combination therapy as soon as possible."
Lancet 2001; 358: 1033?41 "Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack"

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