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Aliskiren and the Calcium Channel Blocker Amlodipine Combination as an Initial Treatment Strategy for Hypertension Control (ACCELERATE): A Randomised, Parallel-Group Trial
Study Questions:
What is the comparative efficacy of a combination of aliskiren and amlodipine to each monotherapy in early control of blood pressure and risk of adverse events?
Methods:
The investigators conducted a double-blind, randomized, parallel-group, superiority trial at 146 primary and secondary care sites in 10 countries, with enrollment from November 28, 2008, to July 15, 2009. Patients eligible for enrollment had essential hypertension, were ages 18 years or older, and had systolic blood pressure between 150 and 180 mm Hg. Patients were randomly assigned (1:1:2) to treatment with 150 mg aliskiren plus placebo, 5 mg amlodipine plus placebo, or 150 mg aliskiren plus 5 mg amlodipine. Random assignment was through a central interactive voice response system, and treatment allocation was masked from the patients. From 16-32 weeks, all patients received combination therapy with 300 mg aliskiren plus 10 mg amlodipine. The primary endpoints, assessed on an intention-to-treat basis (i.e., in patients who received the allocated treatment), were the adjusted mean reduction in systolic blood pressure from baseline over 8-24 weeks, and then the final reduction at 24 weeks.
Results:
A total of 318 patients were randomly assigned to aliskiren, 316 to amlodipine, and 620 to aliskiren plus amlodipine. A total of 315 patients initially allocated to aliskiren, 315 allocated to amlodipine, and 617 allocated to aliskiren plus amlodipine were available for analysis. Patients given initial combination therapy had a 6.5 mm Hg (95% confidence interval [CI], 5.3-7.7) greater reduction in mean systolic blood pressure than the monotherapy groups (p < 0.0001). At 24 weeks, when all patients were on combination treatment, the difference was 1.4 mm Hg (95% CI, −0.05 to 2.9; p = 0.059). Adverse events caused withdrawal of 85 patients (14%) from the initial aliskiren plus amlodipine group, 45 (14%) from the aliskiren group, and 58 (18%) from the amlodipine group. Adverse events were peripheral edema, hypotension, or orthostatic hypotension.
Conclusions:
The authors concluded that routine initial reduction in blood pressure (>150 mm Hg) with a combination such as aliskiren plus amlodipine can be recommended.
Perspective:
The study findings show that patients randomly assigned to initial combination treatment with both aliskiren and amlodipine had substantially better mean blood pressure reduction over the first 24 weeks than did patients starting on either drug as monotherapy, with no increase in adverse events or withdrawals. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) has already recommended the consideration of initial combination treatment in patients who are more than 20/10 mm Hg above target blood pressure, and the European guidelines recommend use of low-dose combinations. Based on this study and others such as ACCOMPLISH, a move toward routine initial reduction of blood pressure with combination therapy should now be considered for all those who are already implementing lifestyle changes and still have blood pressure above 150/90 mm Hg.
Keywords: Hypotension, Orthostatic, Intention, Fumarates, Edema, Blood Pressure, Amlodipine, Hypertension
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