Because many hypertensive patients require multiple drugs to control blood pressure (BP), the relative effectiveness of drug combinations is of interest. In the ACCOMPLISH trial, researchers pitted an angiotensin-converting–enzyme inhibitor plus calcium channel blocker against an ACE inhibitor plus diuretic. The trial was sponsored by a manufacturer of a benazepril–amlodipine combination capsule.
Enrollment criteria included age 
60 and history of hypertension (nearly all patients were already taking antihypertensive drugs at enrollment). In addition, all patients had at least one of the following high-risk criteria: documented coronary disease, history of stroke, peripheral vascular disease, diabetes, left ventricular hypertrophy, elevated serum creatinine, or macroalbuminuria. More than 11,000 patients were randomized to receive either benazepril–amlodipine or benazepril–hydrochlorothiazide, with doses adjusted to achieve normal BP. If additional drugs were needed, β-blockers, 
-blockers, clonidine, spironolactone, and loop diuretics were permitted.
The study was stopped after a mean follow-up of 3 years, when the primary endpoint (fatal plus nonfatal cardiovascular events) had occurred significantly less frequently in the benazepril–amlodipine group than in the benazepril–hydrochlorothiazide group (9.6% vs. 11.8%). Mean BP was 1 mm lower in the former group than in the latter group. Peripheral edema occurred more frequently in the amlodipine group (31% vs. 13%); other side effects occurred with similar frequency in the two groups.
Comment: In this study, the combination of an ACE inhibitor and a calcium channel blocker was superior to the combination of an ACE inhibitor and a diuretic. However, because subjects were older high-risk patients with preexisting target organ damage or diabetes, the results might not apply to lower-risk patients. Before drawing final conclusions, I would like to see additional details not presented in this report. For example, how many patients in each group received nonthiazide diuretics, which might be beneficial for amlodipine recipients (who tended to develop edema) but harmful for thiazide recipients (who would have ended up taking 2 diuretics)? In the meantime, the editorialist — who chaired the 7th Joint National Committee on Hypertension — urges us to not abandon thiazides for hypertension, but hints that future guidelines might not emphasize diuretics as strongly as past guidelines have.
— Allan S. Brett, MD
Published in Journal Watch General Medicine December 16, 2008
Jamerson K et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008 Dec 4; 359:2417.
Chobanian AV. Does it matter how hypertension is controlled? N Engl J Med 2008 Dec 4; 359:2485.
