Reviparin significantly reduces death and repeat heart attacks without increasing the risk of stroke

A major Canadian-led global study has found that an inexpensive anti-blood-clotting drug significantly reduces death and repeat heart attacks without increasing the risk of stroke.

The study is of significance to patients in all countries, including developing countries where access to high-tech treatments for cardiovascular problems may be limited.

The CREATE randomized trial was initiated and coordinated in Canada and enrolled more than 15,500 people in China, India and Pakistan. Heart attack patients were given Reviparin, a low molecular weight heparin, or a placebo, twice daily for seven days.

The four-year study showed that the risk of deaths, heart attacks and strokes were reduced by about one-sixth. This means that treating 1,000 patients for a week would prevent about 15 to 20 individuals from dying or suffering a new heart attack. The study also showed that the benefits were greater, the earlier the treatment was used after the onset of symptoms. In those who were treated within two hours of symptom onset, the death rate was lowered by about 30 per cent.

The study was presented today at the Scientific Sessions of the American Heart Association conference in New Orleans by co-investigators Dr. Salim Yusuf and Dr. Shamir Mehta of the Population Health Research Institute at Hamilton Health Sciences and McMaster University. Dr. Yusuf is a professor of medicine at the Michael G. DeGroote School of Medicine at McMaster University, director of the Population Health Research Institute and holds an endowed chair of the Heart and Stroke Foundation of Ontario. Dr. Mehta is an associate professor of medicine at the Michael G. DeGroote School of Medicine, member of the Population Health Research Institute and a clinician scientist with the Canadian Institutes of Health Research.

"Reviparin is a simple and relatively inexpensive anti-thrombotic therapy, which can be used in both developed and developing countries to reduce mortality for acute myocardial infarction," said Dr. Yusuf. "It is more affordable than newer anti-thrombotics, simple to use and of benefit in addition to the broad range of therapies of proven and established value. It is the only treatment for a heart attack that has been convincingly demonstrated to reduce mortality in a single study over the last decade."

Dr. Mehta said: "The reduction in mortality with Reviparin is truly remarkable since no other drug in this class has shown similar benefits and the fact the drug was tested on top of already proven therapies."

About 15.5 million people die worldwide from cardiovascular deaths each year and about half of these are due to acute myocardial infarction, with the majority occurring in low and middle-income countries, Dr. Yusuf noted.

"Low cost therapies are obviously more invaluable than expensive ones," he said. "This therapy could be used not only in wealthy countries, but also in small medical centres in low and middle income countries. It has the potential to benefit more than a million individuals annually."

In a companion study, also presented today at the American Heart Association meeting, Drs. Mehta and Yusuf evaluated the role of high dose glucose-insulin-potassium (GIK) solution in 20,000 patients. The solution is thought to preserve heart muscle and prevent it from dying during the acute stages of a heart attack.

The study results show that GIK had a neutral effect, but the authors wonder whether a solution that had a lower glucose concentration may be of benefit.

"It is important to conduct large studies of promising agents to determine whether or not they are of value," said Dr. Mehta. "While demonstrating that something is of benefit is wonderful, reliably excluding agents are not helpful is equally important as it will avoid their unnecessary use and associated costs. This is particularly important for therapies such as GIK that may never otherwise be studied because they are of no commercial value but have the promise to help many thousands of lives."

Dr. John Kelton, dean of the Michael G. DeGroote School of Medicine and dean and vice-president, Faculty of Health Sciences, McMaster University, said: "This important study represents one of the first in many years that is bringing in a new drug that will produce a significant reduction in deaths from heart attack. Perhaps more importantly, I see a future treatment given by ambulance attendants where a person suspected of having a heart attack is given an aspirin and an injection of this heparin-like drug. The lives saved in Canada and around the world would be dramatic."

Mr. Murray Martin, President and CEO of Hamilton Health Sciences of Hamilton, said: "Part of our mission as an academic teaching hospital is to advance health care through education and research. We commend Dr. Yusuf and Dr. Mehta for their leadership and commitment to investigating best practices and finding better ways to help people around the world deal with important health issues."