"Benazepril-Amlodipine or Benazepril-Hydrochlorothiazide in High-Risk Patients with Hypertension". The New England Journal of Medicine. 2008.
Links to original sources: Wiki Journal Post Full Journal Article
In patients with hypertension at high risk for cardiovascular events, is a combination therapy of an ACE inhibitor and a dihydropyridine calcium-channel blocker more effective in reducing cardiovascular events than an ACE inhibitor combined with a thiazide diuretic?
In high-risk hypertensive patients, combination therapy with benazepril (an ACE inhibitor) and amlodipine (a calcium-channel blocker) was more effective at reducing cardiovascular events than a combination of benazepril and hydrochlorothiazide (a thiazide diuretic).
Hypertension is a major risk factor for cardiovascular diseases, and treatment often requires a combination of antihypertensive agents to achieve recommended blood pressure targets. While current guidelines include thiazide diuretics in combination regimens, the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial aimed to determine the effectiveness of an alternative combination therapy of benazepril plus amlodipine compared to benazepril plus hydrochlorothiazide.
Current guidelines recommend use of a thiazide diuretic in combination antihypertensive regimens, but the ACCOMPLISH trial suggests an alternative combination therapy that might be superior for certain populations.
Multicenter, double-blind, parallel group, randomized, placebo-controlled trial. N=11,506 patients with high-risk hypertension. Benazepril-amlodipine group (n=5,744) Benazepril-hydrochlorothiazide group (n=5,762) Mean follow-up: 36 months. Primary outcome: composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.
Inclusion Criteria: Patients with hypertension at high risk for cardiovascular events. Exclusion Criteria: Not specified. Baseline Characteristics: Mean age 68.4 years; 39.5% women; diabetic patients accounted for 60.4% of the population.
Benazepril-amlodipine: Patients started on a combination of 20 mg benazepril and 5 mg amlodipine once daily. Benazepril-hydrochlorothiazide: Patients started on a combination of 20 mg benazepril and 12.5 mg hydrochlorothiazide once daily. Doses adjusted to manage blood pressure, with additional antihypertensive agents allowed.
Primary Outcome: After 36 months, the benazepril-amlodipine group had a lower rate of the primary composite outcome than the benazepril-hydrochlorothiazide group (9.6% vs. 11.8%, P<0.001). Secondary Outcome: For the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, the benazepril-amlodipine group had fewer events compared to the benazepril-hydrochlorothiazide group (5.0% vs. 6.3%, P=0.002).
- The study population comprised patients with previous coronary disease and diabetes, which may not fully represent the broader hypertensive population. - The dosing of hydrochlorothiazide may not reflect the optimal dose for cardiovascular benefit.
Supported by Novartis.
Address reprint requests to Dr. Jamerson at the Division of Cardiovascular Medicine, University of Michigan Health System, 24 Frank Lloyd Wright Dr., Lobby M, Ann Arbor, MI 48106, or at emarshal@umich.edu.