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ACE Inhibitor/Diuretic Combination Treatment Protects Against Second Stroke: Presented at ESH

By Bruce Wilson

Special to DG News

MILAN, ITALY -- June 18, 2001 -- A landmark study of more than 6,000 persons with a history of stroke or transient ischemic attack shows that perindopril, with or without the diuretic, indapamide, significantly reduces the likelihood of death, heart attack, or recurrent stroke over five-years of treatment.

Presentation of the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) results was one of the big highlights at the European Society of Hypertension meeting here yesterday (June 17).

The trial enrolled 6,105 patients with a history of any type of stroke or transient ischemic attack (TIA) within five years prior to study commencement. A wide range of baseline blood pressure levels was included, and the study included patients who were hypertensive or non-hypertensive.

After a four-week run-in period with peridopril 4 mg/day, patients were randomized to combination treatment with perindopril (4 mg) plus indapamide (2.0 or 2.5 mg) or matching placebos. Treatment was added onto background standard care, including hypertension medication, if needed.

The average duration of follow-up was four years; all patients were followed-up for as long as possible, irrespective of whether they continued to take their randomized treatments or whether they experienced non-fatal disease events. The primary end point of the study was total stroke; secondary end points included fatal or disabling stroke, major vascular events, dementia and cognitive function, and disability and dependency.

According to study co-principal investigator, Professor Stephen MacMahon, University of Sydney, Sydney, Australia, active treatment reduced the risk of stroke by a highly significant 28 percent (95 percent confidence interval [CI]: 17 percent, 38 percent, p<0.0001).

Risk for major vascular events was reduced by 25 percent (95 percent CI: 16 percent, 33 percent, p<0.0001) and treatment also significantly reduced cognitive decline associated with stroke.

Combination therapy had more benefit than perindopril alone on all end points.

Two particularly striking observations were made during the trial, Dr. MacMahon said. First, was the 87 percent adherence to active medication during the four years of the trial (those taking placebo were 88 percent adherent); second, was that treatment benefitted nonhypertensive patients just as much as it did hypertensive patients, suggesting that the results were not entirely due to the antihypertensive effects of the medications.

Greater benefits were seen in patients with hemorrhagic stroke among Asian patients. All age levels benefitted equally from treatment.

Dr. MacMahon said the results of PROGRESS are "profound" and have large implications for the future of stroke treament.

"Each year there are about 15 million people worldwide who survive a stroke, and the PROGRESS results are of direct relevance to their care," he said. "There is a strong case for making PROGRESS drugs available to most stroke patients, irrespective of their age and blood pressure and irrespective of other treatments they may be receiving."

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