Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial

• the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was designed to test the hypothesis that treatment with an ACE inhibitor combined with amlodipine would result in better cardiovascular outcomes than treatment with the same ACE inhibitor combined with a thiazide diuretic
  • experimental work has shown that the calcium-channel blocker amlodipine effectively increases the availability of vascular endothelial nitric oxide
    • other studies have shown that the combined effects of amlodipine and an angiotensin-converting–enzyme (ACE) inhibitor on nitric oxide are greater than the effect with either drug alone
• in a randomized, double-blind trial, 11,506 patients with hypertension who were at high risk for cardiovascular events were assigned to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide
  • primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization
• baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded
  • 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-hydrochlorothiazide group
  • there were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001)
  • for the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P=0.002)
• the study authors concluded that this trial shows that combination treatment with benazepril plus amlodipine is superior to treatment with benazepril plus hydrochlorothiazide in reducing the risk of cardiovascular events and of death among high-risk patients with hypertension

Notes:

• how do the results from this trial compare with those seen in the ALLHAT study
  • in ALLHAT, amlodipine-based and chlorthalidone-based therapy had similar effects on mortality and on the rates of stroke and myocardial infarction (2)
  • two possible explanations for the difference between the outcomes of this trial and those of ALLHAT
    • chlorthalidone (which was used in ALLHAT) may differ from hydrochlorothiazide (which was used in the ACCOMPLISH trial) in its effect on outcomes independently of its effect on blood pressure
    • the combination of amlodipine with a drug that inhibits the renin–angiotensin system, as compared with amlodipine monotherapy, may provide unique beneficial effects

Reference:

• 1. Jamerson K et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.N Engl J Med. 2008 Dec 4;359(23):2417-28.
• 2. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-2997.