ACE inhibitor calcium channel blocker combo drug shown to reduces heart attacks

Dec 3 2008

While doctors are urged to start with a diuretic-based strategy to control patients' high blood pressure, an international blood pressure study shows a different single-pill drug combination is more effective at preventing heart-related events such as heart attacks and strokes.

The findings challenge the way blood pressure is usually treated worldwide.

The randomized study led by a University of Michigan Health System researcher compared two drug combinations. The results, which appear in today's New England Journal of Medicine, were so significant that the trial was stopped early.

Both single-pill combination drugs helped more than 75 percent of people who had high blood pressure and other cardiovascular risk factors get their blood pressure down. But even more important, patients in the study taking the combination that included a calcium channel blocker had 20 percent fewer heart-related events than the patients taking the other combination.

In all, 11,506 study participants took a single tablet that includes two medications. One group received a tablet containing benazepril, which is a type of drug called an ACE inhibitor, and amlodipine, which belongs to a class of drugs known as calcium channel blockers or CCBs. The other pill combined benazepril and hydrochloro-thiazide, a type of diuretic or "water pill." The 20 percent reduction in cardiovascular events was observed with the ACE/CCB combination tablet.

Cardiovascular events were defined as cardiovascular deaths, heart attacks, strokes, hospitalizations for unstable angina and treatments to re-open blocked heart arteries.

Currently, national guidelines for the treatment of high blood pressure (also called hypertension) call for patients who need medication to start out on a single pill, usually a diuretic, or water pill, and to add other drugs only as needed to bring pressure down. But the new results may signal a need to change those guidelines.

The ACCOMPLISH study suggests physicians no longer give diuretics preferred status in treating patients.

"This robust study showed us that switching patients to a single-pill combination meant that twice as many patients got to their blood pressure goal, regardless of previous therapy," says University of Michigan Health System's Kenneth Jamerson, M.D., the leader of the study.

"The significant reduction in cardiovascular events we observed in patients will, I hope, show physicians that earlier use of a combination medication, especially with amlodipine, may be in the best interest of patients," he says.

Jamerson is a professor of internal medicine at the University of Michigan Medical School and a member of the U-M Cardiovascular Center.

Results from the ACCOMPLISH trial show that just six months of treatment with either drug combination was enough to bring the blood pressure of 73 percent of patients into an acceptable range - despite the fact that two-thirds were already taking some other medication before they entered the study. At the beginning of the trial, only 37 percent had blood pressure below 140/90.

However, by the end of the three-year trial blood pressure control rates were 80 percent, with average systolic blood pressure less than 130 mmHg. This represents exceptional blood pressure control when contrasted to the current control rate of about 30 percent in the United States.

Participants from five countries - the United States, Sweden, Norway, Denmark and Finland - were part of the trial, and all patients were at risk for cardiovascular events.

Many studies have already shown that reducing blood pressure can reduce the risk of stroke, heart attack, heart failure and other conditions, but many people have a very difficult time achieving blood pressure control.

As many as 73 million Americans have high blood pressure. But because high blood pressure doesn't cause symptoms, most people who have it, don't know it.

Over time, uncontrolled blood pressure affects the blood vessel walls, encouraging the growth of weak spots called aneurysms and the formation of narrowed and inflamed areas that can lead to clots that can break off and cause heart attacks and strokes.

Fortunately, once the condition is diagnosed, doctors have a broad range of medicines to choose from to try to get it under control, including many inexpensive generic medicines.

But studies have found that patients often have trouble taking the multiple medications they need. As a result, many companies have developed combination pills.

The study was funded by Novartis, which is among the companies that offer two-drug combination tablets for blood pressure treatment. ACCOMPLISH stands for Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension.

Authors: In addition to Jamerson, ACCOMPLISH investigators included Michael A. Weber, M.D., George L. Bakris, M.D., Björn Dahlör, M.D., Bertram Pitt, M.D., Victor Shi, M.D., Allen Hester, Ph.D., Jitendra Gupte, M.S., Marjorie Gatlin, M.D. and Eric J. Velazquez, M.D.