CHICAGO - A massive study aimed at settling the long-standing debate over the usefulness of calcium antagonists for treating high blood pressure has shown the drugs are part of a safe and effective regimen for patients who don't respond to standard medicines - or who stop taking them because of bothersome side effects, University of Florida researchers report.

The news likely will help physicians better customize therapy for hypertensive patients who also have coronary artery disease, particularly those at high risk of heart attack, stroke or death. Preliminary findings also indicated a calcium antagonist strategy, compared with traditional therapy using beta-blockers and diuretics, prevents diabetes in these patients.

"Now there's an alternative to what's considered the standard of care," said Carl J. Pepine, M.D., the study's principal investigator and chief of cardiovascular medicine at UF's College of Medicine. "The big problem with hypertension is treatment and compliance with treatment. Surveys show that perhaps only 30 percent or less of the patients in the United States who are known to be hypertensive are on treatment and even a smaller percentage are at blood pressure goal for their treatment. It is believed that an important reason for that is the inability to tolerate the treatments. So here we have an alternative treatment strategy that appears to be just as good in terms of preventing adverse outcomes and maybe even better in terms of preventing the emergence of new diabetes cases."

Pepine, the newly installed president of the American College of Cardiology, or ACC, announced the results of the landmark International Verapamil SR-Trandolapril study, funded by Abbott Laboratories and known as INVEST, today at the ACC's 52nd annual Scientific Session in Chicago. More than 50 million Americans have high blood pressure, according to the American Heart Association. Elevated blood pressure is associated with up to half of all cases of coronary artery disease, the No. 1 killer of men and women in the United States.

"We're seeing huge numbers of patients with coronary artery disease and hypertension as our population ages," Pepine said. "The question we ask now is how is their blood pressure best managed? The literature up until the completion of our study was relatively void of evidence-based data in terms of what's best for controlling blood pressure in this population."

Physicians have used calcium antagonists to treat heart-related ailments for more than two decades. Studies have shown calcium antagonists and beta-blockers are of similar benefit for patients with the chest pain known as stable angina pectoris. But beta-blockers have been better for those who have suffered a heart attack. Researchers had not previously put the calcium antagonists classified as nondihydropyridines to the same rigorous scientific test for patients with high blood pressure and heart disease. And in the past, a short-acting dihydropyridine form of the drug was linked to an increased risk of heart attack or death in some patients, raising concerns about their safety.

Calcium antagonists decrease the work of the heart's blood pumping, reduce the pressure of blood flow through the body and improve blood circulation through heart muscle. Since the 1960s, beta-blockers have ranked among the most widely used drugs for the treatment of high blood pressure, but a small percentage of patients can't tolerate them because they develop fatigue or other side effects. The drugs fight the condition by reducing the heart's workload, slowing heart rate and decreasing the force with which the heart muscle contracts. Diuretics lower blood pressure.

In recent years, doctors have reassessed the ideal blood pressure targets. Today, many patients are advised to lower their blood pressure below 130/85 mm Hg, thanks to research that has shown that doing so reduces the incidence of adverse effects or death, especially in patients with diabetes or other complications. That frequently requires the use of multiple medications, sometimes more than three.

In the INVEST study, UF researchers tracked more than 22,500 patients for two to five years to determine whether a high blood pressure treatment strategy that included a sustained-release form of the nondihydropyridine calcium antagonist verapamil was at least as effective as beta-blockers and diuretics at lowering blood pressure below 130/85. Patients at 862 sites around the world were randomly assigned to one of the two treatment strategies.

Those assigned to the verapamil strategy also could receive the drug trandolapril and/or a diuretic to achieve the target blood pressure or minimize side effects. Those in the study's other group also could use trandolapril, an angiotensin-converting enzyme, or ACE, inhibitor, if needed. (ACE inhibitors block an enzyme in the body that causes blood vessels to narrow. If the blood vessels are relaxed, blood pressure decreases and the heart uses less oxygen to pump blood.)

The project was the first prospective study aimed at achieving the blood pressure guidelines set forth in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Researchers found that both approaches controlled high blood pressure exceptionally well, lowering it to target levels in more than 72 percent of study participants, who were mostly elderly.

"Additionally, we found that the blood pressure lowering that was achieved in both strategies of the trial was very good compared to other trials," Pepine said, adding that the calcium antagonist strategy was just as good at preventing adverse outcomes such as heart attack, stroke or death during the study as the traditional approach.

Scientists also were intrigued to learn new cases of diabetes occurred less frequently among those assigned to the calcium antagonist regimen. Many heart disease patients with high blood pressure are at greatly increased risk of developing diabetes, which is rapidly nearing epidemic rates in the United States. Preventing diabetes would have tremendous public health implications, Pepine said, and could greatly reduce related health-care costs.

The clinical trial was the first coronary artery disease study to adequately represent women and minorities, UF researchers said. A little more than half of the participants were women, and nearly half were Hispanic or black.

For more information contact: Melanie Fridl Ross, (352) 690-7051, e-mail: ufcardiac@aol.com or
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