Combination therapy initially, best for blood pressure control: ACCELERATE study

By Dr. Ananya Mandal, MDJan 13 2011

A new study published online Jan. 13 in The Lancet shows that patients with high blood pressure respond better to a combination drug therapy than those on monotherapy. Also patients who undergo the two-drug treatment after taking the single-drug therapy also experience better blood pressure outcomes, though not at the same level as those who began with the combination treatment, according to research.

Morris J. Brown, of the University of Cambridge in the United Kingdom, and colleagues looked at outcomes of 315 patients randomly assigned to aliskiren, 315 to amlodipine, and 617 to a combination of the two. The patients were from 146 sites in ten countries between Nov. 28, 2008 and July 15, 2009. All patients received combination therapy starting at week 16 of the 32-week trial. All patients enrolled had essential hypertension, were aged 18 years or older, and had systolic blood pressure between 150 and 180 mm Hg. Results showed that combination therapy had a greater reduction in mean systolic blood pressure than the monotherapy groups by 6.5 mm Hg. By week 24, when all patients were receiving combination therapy, the difference between groups had fallen to 1.4 mm Hg.

The researchers write, “Our 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 cost in adverse events or withdrawals. Once the monotherapy patients progressed to combination therapy, their blood pressure fell towards, but never numerically caught up with, that of the initial combination group.” Withdrawal rates due to adverse events including, peripheral edema, hypotension and orthostatic hypotension, were similar across all treatment groups. The trial was funded by Novartis Pharma AG.

Ivana Lazich of the University of Chicago's Hypertensive Diseases Unit and George Bakris, of the University of Chicago Pritzker School of Medicine in an accompanying editorial explain that results from ACCELERATE support existing data from the SHIELD and ACCOMPLISH trials. They also noted that ACCELERATE randomized more patients, had a longer follow-up period and was representative of the general population. The editorial reads, “ACCELERATE puts into proper context the importance of starting with combination anti-hypertensive to lower BP towards guideline goals for the general population… Monotherapy, even when maximally titrated and with add-on agents, generally does not provide the same level of control and risk reduction in people who are 20/10 mm Hg above their goal.”  They added that this could call for a change of guidelines, advocating initial combination therapy for patients already implementing lifestyle changes who have BP greater than 150/90 mm Hg.