Rx CARE

AHA's stroke guidelines have recommendations for diabetics

Stroke is one of the deadliest fates that can confront an individual with diabetes. Though nondiabetic patients are significantly less vulnerable to stroke, stroke ranks as the third most common cause of death in the United States today. The American Heart Association (AHA) estimates that the economic burden in direct and indirect costs of strokes was $51 billion in 1999 alone. Unfortunately, epidemiological data suggest a leveling off of improvement in stroke mortality at the same time the incidence of stroke is expected to increase.

To squelch this negative trend, AHA recently released a comprehensive scientific statement entitled Primary Prevention of Ischemic Stroke.

"The novel issue that came up was of using ramipril [Altace by Wyeth-Ayerst/King] in diabetes patients—because of the Heart Outcomes Prevention Evaluation, or HOPE, trial," said Michael Davidson, M.D., FACC, a board-certified cardiologist and president/CEO of the Chicago Center for Clinical Research. The HOPE trial showed a 33% reduction in stroke risk in individuals with diabetes who took 10 mg of ramipril daily (dosing was gradually increased from 2.5 mg). The risk of death from cardiovascular disease, myocardial infarction, and stroke was also reduced in this population.

This risk reduction appeared to be independent of ramipril's effect in decreasing blood pressure. Davidson speculated that ramipril's effect in reducing the risk of stroke probably occurs at the endothelium of the artery wall. "It either reduces the atherosclerotic accumulation, which should reduce the risk of stroke, or in some way it allows the healthy endothelium to prevent clots, or to maintain vasodilation," he said.

While AHA recognizes the results of the HOPE trial as an exciting development in the prevention of cardiovascular disease and stroke prevention in diabetes patients, the recommendation is more general, calling for careful control of hypertension for both Type 1 and Type 2 diabetes. Another study will be under way to compile more data about ramipril's preventive effects.

AHA continues to recommend glycemic control to reduce microvascular complications. In addition, AHA recommendations endorse the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, & Treatment of High Blood Pressure as well as the National Cholesterol Education Program II Guidelines. The guidelines also recommend antithrombotic therapy (warfarin or aspirin) for patients with nonvalvular atrial fibrillation based on an assessment of the risk of embolism and bleeding complications.

Nevertheless, the topic most clinicians and researchers appear to be discussing is: Does ramipril's effect in reducing the risk of stroke generalize to the entire class of ACE inhibitors? Davidson commented, "We don't know if the data can be extrapolated across the ACE inhibitor class or not," though he expects most physicians to ascribe to an ACE class effect, particularly if any other ACE inhibitor trial demonstrates a similar outcome.

A large trial, the Prevention of Events with Angiotensin-Converting Enzyme inhibition (PEACE), with the ACE inhibitor trandolapril (Mavik, Knoll), should provide some information when it is completed.

Michelle Booth, Pharm.D., of Advanced Pharmacy Concepts, Narragansett, R.I., expects most prescribers to treat the effect of ramipril as a class effect. "I would think that in the beginning there might be some people who say, 'OK, we need to prescribe just the ramipril because these patients are at risk for stroke and they have diabetes.' But, I don't perceive that physicians are going to change people's therapy," she said. "I don't know that it's going to change the thinking of the prescribers that it is a class effect with the ACE inhibitors."

Kathy Hitchens, Pharm.D.

Based in Indiana, the author writes frequently on clinical issues.

Kathy Hitchens. AHA's stroke guidelines have new recommendations for diabetics.

Drug Topics

2001;3:27.