ACCOMPLISH may lead to single pill therapy for hypertensive patients

CHICAGO—The interim results of ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving with Systolic Hypertension), the first trial to evaluate cardiovascular outcomes using single pill, fixed-dose combination therapy for the treatment of high-risk hypertensive patients, were presented Monday at the American College of Cardiology (ACC) Scientific Sessions by Kenneth Jamerson, MD, who also spoke with Cardiovascular Business News about the impact of the trial. 

The interim results showed that patients with hypertension and high risk for cardiovascular complications experienced 20 percent fewer events (cardiovascular death, heart attacks, strokes, hospitalizations for unstable angina and need for coronary heart procedures) when treated with a combination of an ace inhibitor and calcium channel blocker (ACE/CCB) compared to a combination of an ace inhibitor and hydrochlorothiazide (ACE/HCTZ).

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. They recognized that one arm was clearly benefitting, showing a clear 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 told Cardiovascular Business News.

Jamerson said that the last patient had their last visit 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, “Seventh Report of High Blood Pressure” (JNC 7), state that diurectics should be the mainstay of any initial combination drug regimen and recommend initial treatment with tablets that contain one drug.

Regarding the guidelines, Jamerson said that “the results should challenge them in a major way, but we can’t expect any changes until we produce the completed document, and those who write the guidelines are allowed to examine our evidence. Ultimately, I believe once they’ve had the opportunity to examine the evidence, 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 complication 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 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 Novartis-funded investigators concluded that the results of ACCOMPLISH provide compelling evidence for initial combination therapy with ACE/CCB.
 
Jamerson said that “these exciting results will mean better outcomes for the patient with fewer tablets.”

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