Before this trial, no single antihypertensive was proven to be significantly better than others. The ALLHAT Trial, which was published in 2002, did not clearly demonstrate a difference between a single agent diuretic, an ACE inhibitor, or a calcium channel blocker (CCB). At the time, JNC 7 recommended combination blood pressure regimens for those with BP >20/10 above target and that diuretics should be considered. Experimental evidence prior to this trial, though, showed that CCBs increased vascular endothelial nitric oxide and that the addition of an ACE inhibitor increases nitric oxide levels more than either drug alone. This combination was shown in laboratory animals to slow the progression of atherosclerotic lesions and in humans, this combination reduced LVH and arterial stiffness. Because of these findings, it was proposed that combinations that do not include diuretics be considered.
The ACCOMPLISH Trial enrolled 11,506 patients and randomized them to getting either benazepril and amlodipine or benazepril and hydrochlorothiazide. The inclusion criteria were patients at least 55 years with HTN and high CV risk. The primary outcome was the time to first CV event (defined as the composite of a cardiovascular event and death from cardiovascular causes). The trial was terminated early after a mean follow-up of 36 months.
The primary outcome events were lower in the benazepril + amlodipine group than the benazepril-HCTZ group, 9.6% versus 11.8 (~20% reduction in primary outcome). One criticism of the trial was the use of the short-acting diuretic hydrochlorothiazide rather than the longer-acting chlorthalidone. It's said that this may have contributed to the worse event rate with benazepril + hydrochlorothiazide group. Evidence to support this concern was the fact that the MRFIT trial which was published in 1990 changed its protocol to include chlorthalidone rather than hydrochlorothiazide because of a nonsignificant trend towards worst outcomes of hydrochlorothiazide. Despite these concerns, a 2010 follow-up study from the ACCOMPLISH trial offers measured blood pressure continuously in 573 patients and there is no difference in 24 hour blood pressures for either group — indicating that the findings of the trial were more sound than detractors would make it out to be (Jamerson 2011).
The ACCOMPLISH Trial: Jamerson, K., Weber, M. A., Bakris, G. L., Dahlöf, B., Pitt, B., Shi, V., ... & Velazquez, E. J. (2008). Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. New England Journal of Medicine, 359(23), 2417-2428.
ACCOMPLISH Trial PMID: 19052124
Useful Summaries of the ACCOMPLISH Trial: Wiki Journal Club
Other References:
Jamerson, K. A., Devereux, R., Bakris, G. L., Dahlöf, B., Pitt, B., Velazquez, E. J., ... & Weber, M. A. (2011). Efficacy and duration of benazepril plus amlodipine or hydrochlorthiazide on 24-hour ambulatory systolic blood pressure control. Hypertension, 57(2), 174-179.