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Significant Stroke Prevention Noted With Ramipril

Patients at high risk of stroke should be treated with the ACE inhibitor ramipril, trials at 267 hospitals in 19 countries has shown.

"Our results indicate that patients who are at high risk of stroke should be treated with ramipril, irrespective of their initial blood pressure levels and in addition to other preventive treatments such as blood pressure lowering agents or aspirin," declares Dr Jackie Bosch, Canadian Cardiovascular Collaboration, McMaster University, Hamilton, Ontario, and lead author of the report.

"Widespread use of an angiotensin converting enzyme inhibitor such as ramipril in patients at high risk of stroke is likely to have a major impact on public health."

The international investigation was among 9, 297 patients with vascular disease, or diabetes, plus an additional risk factor, followed for 4.5 years. The cohort is part of the HOPE study, a double blind randomised trial with a two by two factorial design, in which participants were randomised to receive up to 10 mg of ramipril, 400 IU of vitamin E, both, or matching placebos.

Stroke is the second leading cause of death in the world and of disability in developed countries. In North America alone, 550,000 new stroke cases are reported each year and there are approximately five million people who have had a stroke, 60 percent of whom have some residual disability.

The most recent data indicates that ACE inhibitors reduce proliferation of vascular smooth muscle, enhance endogenous fibrinolysis, have the potential to stabilize plaques, and decrease angiotensin II mediated atherosclerosis, plaque rupture, and vascular occlusion.

Dr Bosch found, in the trial, that while there was a modest reduction in blood pressure, the risk of any stroke was reduced by 32 percent in the ramipril cohort compared with the placebo group. Risk of fatal stroke was reduced by 61 percent. In addition, significantly fewer patients in the ramipril cohort suffered mental or functional impairment.

An impact is seen early and benefits to patients continued throughout the study period. Benefits of ramipril are consistent in patients with and without previous stroke, previous manifestation of any cerebrovascular disease, coronary artery disease, peripheral arterial disease, or diabetes.

"This suggests that our results are broadly applicable to patients at high risk of stroke with diverse presentations and a range of background treatments," the clinicians declare.

The study to evaluate carotid ultrasound with ramipril and vitamin E (SECURE) showed a dose dependent, but blood pressure independent, reduction in carotid artery intima medial thickness.

"As stroke is the leading cause of disability in developed countries, even moderate decreases in disability would be of global importance, Dr Bosch and colleagues conclude.
BMJ 2002; 324: 699-702. "Use of ramipril in preventing stroke: double blind randomised trial"

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