Thursday, March 12, 2009

Final Results of ACCOMPLISH Show Benefit of Fixed-Dose Combination as Initial Therapy

The main results of the ACCOMPLISH trial, which demonstrated the superiority of a combination of initiating antihypertensive therapy with an ACE inhibitor plus a calcium channel blocker (CCB) over initiating with a thiazide-type diuretic, have been published in The New England Journal of Medicine, approximately 9 months after preliminary findings were presented at the annual Scientific Sessions of the American College of Cardiology. These results challenge current US hypertension guidelines, which recommend inclusion of a diuretic in first-line combination therapy.

Between 2003 and 2005, the international ACCOMPLISH trial randomized 11,506 patients with hypertension (mean age 68.4 years) who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide (HCTZ) as single capsule formulations. The only other antihypertensive medications permitted were beta-blockers, alpha-blockers, clonidine, and spironolactone. The trial was terminated early, after a mean follow-up of 36 months, when an interim analysis showed overwhelming efficacy in favor of the benazepril-amlodipine combination. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-HCTZ group. Rates of blood pressure control (<>

The primary endpoint was the composite of death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) compared with 679 in the benazepril-HCTZ (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6%. For the secondary endpoint of death from cardiovascular causes, nonfatal MI, and nonfatal stroke, the hazard ratio was 0.79. Rates of adverse events were similar in the 2 treatment groups and consistent with those observed from clinical experience with the drugs.

In a press release issued by the University of Michigan Health System, Ann Arbor,  lead investigator Kenneth Jamerson, MD, said, "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. 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."

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