Trial suggests single pill hypertension treatment can lead to better CV health. Source: ABC News

CHICAGO—The interim results of the ACCOMPLISH trial showed that patients with hypertension and high risk for cardiovascular complications experienced 20 percent fewer events when treated with a combination of an ace inhibitor and calcium channel blocker (ACE/CCB) compared to a treatment of an ACE inhibitor and hydrochlorothiazide (ACE/HCTZ), according to a presentation on Monday at the American College of Cardiology (ACC) meeting.

The ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving with Systolic Hypertension) trial is the first to evaluate cardiovascular outcomes (cardiovascular death, heart attacks, strokes, hospitalizations for unstable angina and need for coronary heart procedures) using single pill, fixed-dose combination therapy for the treatment of high-risk hypertensive patients.

The study included 11,462 trial participants from the U.S. and the Nordic countries, with an average age of 68, who received either a combo treatment, or the standard guideline treatment.

In, October 2007, the Data and Safety Monitoring Board recommended the termination of the trial, about six months prior to expected conclusion.

“From the beginning of each trial, they monitor the data and safety progression, but the board is unaware which arm they are monitoring because they are simply designated as Treatment X or Y,”  lead investigator Kenneth Jamerson, MD, told Cardiovascular Business News. “They recognized that one arm was clearly benefiting, showing a trend of improvement, while the other was in danger of putting patients at risk. They alerted us [the investigators] to the problem, and we decided to terminate the trial.”

Jamerson from the University of Michigan in Ann Arbor said that the last patient visit occurred on Jan. 24, and despite the termination, the interim analysis provided 95.3 percent of end points adjudicated.

The ACCOMPLISH investigators demonstrated that the ACE/CCB tablet not only reduced death from heart attacks, but also retarded the progression of heart disease by reducing the number of heart attacks, hospitalizations for unstable heart blockages and even the need for procedures to open clogged arteries to the heart, according to the researchers.

However, the strategies used in ACCOMPLISH differ from the current guidelines most clinicians follow. The current guidelines from the National Heart, Lung and Blood Institute, “Seventh Report of High Blood Pressure” (JNC 7), state that thiazide-type diurectics should be the mainstay of any initial combination drug regimen and recommend initial treatment with tablets that contain one drug, or in combination with an agent from another class.

”The ACCOMPLISH results should challenge the guidelines in a major way, but we can’t expect any changes until we produce the completed document,” Jamerson said. “Those who write the guidelines are allowed to examine our evidence and once they do, they will not be able to ignore the effectiveness of this treatment.”

Jamerson said that industry has a consistent mantra of start slow, and continuously add-on medications. “However, you can never catch up to the blood pressure problem with this method,” he said, adding that the ideology behind blood pressure treatment was not wrong previously, there was simply no evidence to the contrary.

In real-world populations, most people with hypertension do not have adequate control of their blood pressure, which was mirrored in the trial—only 37 percent of the participants in the ACCOMPLISH trial had adequate control prior to entry into the trial. However, the trial arm that used the combination tablets as the initial drug treatment, 80 percent achieved adequate control.

The investigators concluded that the results of ACCOMPLISH provide compelling evidence for initial combination therapy with ACE/CCB.
 
Jamerson said that these “results will mean better outcomes for the patient with fewer tablets.”

Yet, changes are not necessarily imminent. Daniel Jones, MD, a University of Mississippi blood pressure specialist and president of the American Heart Association told the Associated Press that the findings could shape treatment guidelines due to be reviewed in a few months.

Doctors can start with a combination, but few do, partly for lack of evidence, he said.

Novartis paid for the study, and most of the investigators are consultants to the pharmaceutical company, which sells Lotrel, the combination drug that proved effective in the trial.