By Bruce Sylvester
CHICAGO -- April 4, 2008 -- Patients with hypertension who are at high risk for cardiovascular (CV) complications can achieve a significant reduction in CV events with a combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker (CCB) compared with a combination of an ACE inhibitor and a hydrochlorothiazide (HCTZ).
Researchers from the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial reported these findings here on March 31 at the American College of Cardiology (ACC) 57th Annual Scientific Session.
The study was terminated early for efficacy.
"ACCOMPLISH shows the superiority of an ACE inhibitor and [CCB], a fixed-dose combination treatment strategy for lowering cardiovascular morbidity and mortality. It also, crucially, suggests direction for modification of hypertension treatment guidelines," said lead investigator Kenneth Jamerson, MD, Professor of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan.
In a late-breaking clinical trial session, Dr. Jamerson noted that the purpose of the study was to determine whether amlodipine besylate/benazepril would be superior in reducing CV morbidity and mortality in high-risk hypertensive subjects when compared with benazepril/HCTZ.
The investigators enrolled 11,462 hypertensive subjects from the United States and from Denmark, Finland, Norway, and Sweden, who were at high CV risk. They initiated study medication after 1:1 randomisation into 2 cohorts, and there were no wash-out or run-in phases to the trial. The randomisation procedures were centralised, and the study was double blinded.
The study was designed with a planned mean observation period of 36 months and a 90% power to detect a 15% reduction in the composite endpoint (CV mortality, stroke, myocardial infarction, coronary revascularisation, unstable angina, and resuscitation from death).
Independent external committees adjudicated and maintained emerging data on the primary efficacy variables.
On October 15, 2007, the Data Safety and Monitoring Committee observed that, after receipt of 60% of the expected data, a prespecified efficacy boundary for the primary endpoint had been crossed and recommended termination of the trial. The recommendation was endorsed by the executive committee.
The investigators reported that the combination of an ACE inhibitor and CCB was superior to the combination of the diuretic and ACE inhibitor for reducing CV morbidity and mortality by 20% (P < .0001).
Dr. Jamerson added, "ACCOMPLISH was an innovative hypertension trial design, with initial combination rather than monotherapy, and it challenges the current standard of care for the management of hypertension with diuretic-based therapy."
Funding for this study was provided by Novartis.
[Presentation title: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension, the Early Termination of the ACCOMPLISH Trial for Efficacy. Abstract 407-2]
E-Mail this DGDispatch to a colleague
