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Combination therapy for hypertension

What's the best drug combination with an ACE inhibitor for treatment of hypertension in patients at risk for cardiovascular disease? Current guidelines recommend a diuretic, as witnessed by the number of ACE inhibitor/diuretic combination products that are currently marketed. However, a new study suggests that the calcium channel antagonist may be a better selection than a diuretic. Researchers from several medical schools in the United States and Sweden randomized 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary endpoint was a composite of death from cardiovascular causes, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization. The average patient was 68 years old at entry and the group included patients with a history of ischemic heart disease, peripheral vascular disease, stroke, LVH, and diabetes. The study was terminated early after 3 years when it was found that the benazepril/amlodipine group had a significantly lower risk of the primary endpoint: 9.6% vs 11.8% (hazard ratio 0.80; 95% confidence interval, 0.72-0.92; P = 0.002). This represents a 2.2% absolute risk reduction and a 19.6% relative risk reduction in the benazepril/amlodipine group vs benazepril/hydrochlorothiazide. The authors conclude that the combination of benazepril/amlodipine is superior to benazepril/hydrochlorothiazide in reducing cardiovascular events in patients with hypertension who are at risk (Jamerson K, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high risk patients. N Engl J Med 2008;359:2417-2428). An accompanying editorial from the chair of the seventh report of the Joint National Committee on hypertension suggests it is time to re-examine the recommendation of initial therapy with a thiazide-type diuretic. He also states, however, that regardless of the drugs chosen for treatment of hypertension, the most important factor is reducing blood pressure to goal levels (Chobanian AV. Does it matter how hypertension is controlled? N Engl J Med 2008;359:2485-2488).