Patients with high systolic BP who were assigned to combination therapy with aliskiren and amlodipine, achieved lower BP faster than those assigned to single therapy with either drug, study findings indicate.
“Our findings show that patients randomly assigned to initial combination treatment with both aliskiren and amlodipine had substantially better mean BP reduction over the first 24 weeks than did patients starting on either drug as monotherapy with no cost in adverse events or withdrawals,” Morris J. Brown, MD, of the University of Cambridge, and colleagues from the United Kingdom wrote in Lancet.
The researchers enrolled patients who had systolic BP between 150 and 180 mm Hg in the double blind, parallel group superiority trial from 146 sites in ten countries between Nov. 28, 2008 and July 15, 2009.
Patients were randomly assigned to 150 mg aliskiren plus placebo (n=315), 5 mg amlodipine plus placebo (n=315), or 150 mg aliskiren plus 5 mg amlodipine (n=617). Doses were doubled after eight weeks of treatment, and after 16 weeks all patients received a combination of 300 mg aliskiren plus 10 mg amlodipine.
If patients had systolic BP greater than 140 mm Hg or diastolic BP greater than 90 mm Hg after at 24 weeks, they were assigned to an add-on treatment (12.5 mg hydrochlorothiazide or placebo).
The researchers found that patients in the initial combination therapy group had a 6.5 mm Hg greater reduction in mean systolic BP compared with the monotherapy groups (95% CI: 5.3-7.7; P<.0001).
At 24 weeks, after all patients were receiving combination therapy, this disparity was smaller; patients in the combination group had a 1.4 mm Hg greater systolic BP reduction (95% CI:-0.05-2.9; P=0.059) than those who started on monotherapy. “Once the monotherapy patients progressed to combination therapy, their BP fell towards, but never numerically caught up with, that of the initial combination group,” the researchers wrote.
Withdrawal rates due to adverse events including, peripheral oedema, hypotension and orthostatic hypotension, were similar across all treatment groups.
In an accompanying editorial, Ivana Lazich, MD, of the University of Chicago’s Hypertensive Diseases Unit and George Bakris, MD, of the University of Chicago Pritzker School of Medicine, explain that results from ACCELERATE support existing data from the SHIELD and ACCOMPLISH trials.
They point out that ACCELERATE randomized more patients, had a longer follow-up period and was representative of the general population.
“ACCELERATE puts into proper context the importance of starting with combination antihypertensives to lower BP towards guideline goals for the general population,” Lazich and Bakris wrote. “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 called for a change of guidelines, advocating initial combination therapy for patients already implementing lifestyle changes who have BP greater than 150/90 mm Hg.