News:Dual therapy better than monotherapy to treat hypertension in the ACCOMPLISH trial

March 31, 2008 By Lauren Ciaglo [mailto:lciaglo@perfuse.org]

The trial was terminated early (October 15, 2007) per the recommendation of the Data Safety and Monitoring Committee because a pre-specified efficacy boundary for the primary endpoint had been reached with only 60% of the expected information for the trial collected.

The current standard of care for hypertensive patients recommends monotherapy treatment (with tablets that contain one drug), which is most commonly a diuretic. The ACCOMPLISH (Avoiding Cardiovascular Events Through COMbination Therapy in Patients LIving with Systolic Hypertension) investigators demonstrated that the ACE inhibitor/calcium channel blocker dual therapy reduced death from myocardial infarction (MI). Furthermore, dual therapy slowed the progression of cardiovascular disease by reducing the number of MIs, cardiovascular hospitalizations, and the need for percutaneous coronary intervention (PCI).

This study was a randomized, multi-national, double-blinded study. Patients age 60 or greater with at least one or 55 years or greater with at least two of the following: history of diabetes, coronary heart disease [myocardial infarction (MI), coronary revascularization, or unstable angina], stroke, peripheral artery disease, left ventricular hypertrophy (LVH), proteinuria, and/or chronic renal insufficiency were enrolled in the study and randomized to receive combination treatment of either an ACE inhibitor (benazepril)/calcium channel blocker (amlodipine besylate) or an ACE inhibitor/hydrochlorothiazide.

Patients received aggressive medical management prior to their entry into the trial and concomitant medications included 78% of patients on an ACE/ARB inhibitor, 67% of patients on lipid-lowering agents, 63% of patients on anti-platelet therapy, and the mean LDL was 101.6 mg/dL.

The primary endpoint for the trial was the composite of cardiovascular morbidity and mortality defined as cardiovascular (CV) death, fatal/non-fatal MI, fatal/non-fatal stroke, hospitalization for unstable angina, coronary revascularization procedure (PCI or CABG).

A total of 11,462 patients were recruited for the trial; however, 11,290 were available for the intent-to-treat analysis with some patients’ data being lost to follow-up (n=114), Hurricane Katrina (n=21), closed sites (n=21), or withdrawn consent n=18). The planned mean observation was 36 months and had 90% power to detect a 15% reduction in the composite primary endpoint.

At the time of the trial termination, the intent-to-treat analysis demonstrated a risk ratio of 1.21 (1.06-1.37) for the primary composite endpoint of CV mortality/morbidity. The risk ratios for the individual components of the endpoint were as follows: CV mortality 1.34 (0.98-1.84), non-fatal MI 1.09 (0.82-1.45), non-fatal stroke 1.22 (0.91-1.63), hospitalization for UA 1.36 (0.87-2.13), coronary revascularization 1.11 (0.95-1.30), and resuscitated sudden death 0.27 (0.08-0.97).

The ACCOMPLISH trial is the first trial to evaluate CV outcomes using single pill, fixed dose combination therapy for the treatment of high risk hypertensive patients. The results of the interim analysis demonstrate that the combination therapy of an ACE inhibitor/calcium channel blocker is superior to the combination of an ACE inhibitor/hydrochlorothiazide. Importantly, the results of the ACCOMPLISH trial challenge the current diuretic based standard of care by providing compelling evidence for initial combination therapy with an ACE inhibitor and calcium channel blocker.

Source

 * 1) Late Breaking Clinical Trials Session: ACC, March 31, 2008 Chicago