The ACCOMPLISH trial: ACE inhibitors and calcium channel blockers for hypertension [Classics Series]

1. Benazepril plus amlodipine offers the same effect at reducing blood pressure in hypertensive patients as benazepril plus hydrochlorothiazide.

2. Benazepril plus amlodipine was more effective than benazepril plus hydrochlorothiazide at reducing cardiovascular events in hypertensive patients at risk for such events.

Original Date of Publication: December 2008

Study Rundown: The Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial sought to compare a thiazide with a calcium channel blocker (CCB) as combination therapy with an angiotensin-converting-enzyme (ACE) inhibitor in reducing cardiovascular events in patients with hypertension. Patients with hypertension and cardiovascular risk factors were randomized to treatment with benazepril plus amlodipine or benazepril plus hydrochlorothiazide (HCTZ). In summary, patients in the benazepril-amlodipine group experienced significantly lower rates of the primary outcome compared to those in the benazepril-HCTZ group (HR 0.80; 95%CI 0.72-0.90). This was due to a significant reduction in the rates of fatal/nonfatal myocardial infarction, while there was no significant difference in the rate of death from cardiovascular causes. This study demonstrated that adding a CCB to an ACE inhibitor reduces the risk of myocardial infarction when compared to adding a thiazide diuretic for blood pressure control in hypertensive patients. It is important to note that Novartis was significantly involved in the execution of the study – from coordination to data analysis. Moreover, the study was stopped early by the executive committee, as preliminary results met premature termination conditions.

Click to read study in NEJM

In-Depth [randomized, controlled trial]: A total of 11,506 patients from 548 centres in the United States, Sweden, Norway, Denmark, and Finland were randomized to receive either 1) benazepril plus amlodipine or 2) benazepril plus HCTZ. Patients were started on therapy with either benazepril 20 mg and amlodipine 5 mg daily or benazepril 20 mg and HCTZ 12.5 mg daily. Patients were eligible if they had hypertension, a history of coronary events/myocardial infarction/revascularization/stroke, impaired renal function, peripheral artery disease, left ventricular hypertrophy, or diabetes mellitus. Medication doses were adjusted in the first 3 months to maintain a blood pressure ≤140/90, or ≤130/80 in patients with diabetes and kidney disease. Patients were followed every 6 months, and dose adjustments were performed during these visits. The primary endpoint was a composite of cardiovascular events or death from cardiovascular causes. Of note, the study was funded by Novartis, which was also involved in overseeing coordination, data gathering, and data analysis.

Mean blood pressures were 131.6/73.3 mmHg in the benazepril-amlodipine group and 132.5/74.4 mmHg in the benazepril-hydrochlorothiazide group. The mean difference in blood pressure was 0.9 mm Hg systolic and 1.1 mm Hg diastolic (p<0.001). The trial was terminated early by the executive committee. Patients in the benazepril-amlodipine group experienced a significantly lower rate of the primary endpoint as compared with patients in the benazepril-HCTZ group (HR 0.80; 95%CI 0.72-0.90), with an absolute risk reduction of 2.2%. This difference was due to a significant lower rates of fatal and nonfatal myocardial infarction in the benazepril-amlodipine group (HR 0.78; 95%CI 0.62-0.99), while there was no significant difference between the two groups in death from cardiovascular causes.

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