DOCTOR'S VIEW ARCHIVE
Just as many people now take an aspirin a day to keep heart attacks away, millions may soon also be taking another drug daily to ward off heart disease, stroke and diabetes. It is a drug that has been used since 1991 to treat patients with heart disease or high blood pressure. The drug is called ramipril. It is sold by King Pharmaceutical, in the U.S.A, and marketed by Hoechst Marion Roussel outside the U.S.A.
Ramipril appears able to reduce the risk of heart attack, stroke and death by more than 20% in a wide range of patients not traditionally considered to be candidates for the therapy. Ramipril also seems to be the first drug known to prevent the onset of diabetes.
This is the gist of a report released by The New England Journal of Medicine on November 10, 1999, over two months before the scheduled publication of the article on January 20, 2000. The journal took this unusual action because of the potential importance of the new information in treating patients.
The report came from The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Dr. Salim Yusuf of McMaster University, Hamilton, Canada wrote the manuscript along with Peter Sleight, Janice Pogue, Jackie Bosch, Richard Davies, and Gilles Dagenais.
A Large Study with Over 9,000 Patients
Over 9,000 high risk patients from 19 countries in North America, South America, and Europe took part in the 5-year study. They were deemed "high risk" because they had vascular disease or diabetes plus one other cardiovascular risk factor, such as high blood pressure, elevated cholesterol or smoking. None of the patients had heart failure, a common reason for treatment with ramipril, one of the ACE inhibitor family of drugs. Each patient received daily ramipril or a placebo (dummy) during the study.
Ramipril was found to cut the risk of death from cardiovascular disease by 25%, heart attack by 20%, and stroke by more than 30%. Ramipril also cut the need for heart bypass surgery and coronary angiography, decreasing the proportion of patients who required revascularization procedures by 16%. Patients on ramipril had a 30% lower risk of developing diabetes, making it the first drug ever to be effective in preventing the onset of diabetes.
Ramipril Works as an ACE Inhibitor
Ramipril is an ACE inhibitor. It inhibits angiotensin converting enzyme (ACE) which is important to the formation of angiotensin II. Angiotensin II causes arteries in the body to constrict and raises the blood pressure. ACE inhibitors such as ramipril lower blood pressure by inhibiting the formation of angiotensin II and relaxing the arteries.
The results with ramipril fit with another study called the Captopril Prevention Project, which revealed a lower rate of newly diagnosed diabetes in patients who received captopril (marketed as Capoten). The results also fit with those from other trials, which reported that treatment with an ACE inhibitor slowed the progression of kidney disease among patients with type 2 diabetes.
Another Old Drug with New Uses
Earlier in 1999 The New England Journal of Medicine lifted the embargo on another article about an advance in the use of an old drug. It involved a drug called spironolactone that had been marketed under the brand name of Aldactone and was available as a generic drug. The news was that spironolactactone is a major help in treating congestive heart failure and its beneficial effects are additive to those from ACE inhibitors in treating heart failure.
It is a banner year for the pharmaceutical companies, doctors and particularly for all of us as patients when two old drugs find such important new uses.
Reference: Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on death from cardiovascular causes, myocardial infarction, and stroke in high-risk patients. New Engl J Med (Jan 20, 2000) in press.