Using combination therapy—aliskiren and amlodipine—for the initial reduction of blood pressure (BP) (that is greater than 150 mm Hg) can be more effective than monotherapy alone, according to the ACCELERATE study published in the Jan. 12 issue of the Lancet.
“Hypertension is a complex disorder, and target blood pressure in most patients cannot be achieved with monotherapy,” the authors wrote. “Yet, guidelines give muted advice on starting treatment with a combination of drug classes, and only the beta-blocker–diuretic combinations are licensed for this use in the U.K.”
To better understand the effectiveness of using a combination therapy to lower BP, Morris J. Brown, MD, of the University of Cambridge in the U.K., and colleagues conducted a double-blind, randomized trial on 1,247 patients at 146 primary and secondary care sites in 10 countries between Nov. 28, 2008, and July 15, 2009, to assess whether a combination of aliskiren (Tekturna, Novartis) and amlodipine (Norvasc, Pfizer) was more effective than each monotherapy alone.
Researchers randomly assigned patients at a 1:1:2 ratio to receive either 150 mg aliskiren plus placebo (315 patients), 5 mg amlodipine plus placebo (315 patients) or a combination of 150 mg aliskiren plus 5 mg amlodipine (617 patients).
All enrolled patients had a systolic BP that was between 150 and 180 mm Hg and a diastolic BP that was below 110 mm Hg. The trial’s primary endpoint was the mean reduction of systolic BP from baseline over eight to 24 weeks.
The researchers found that the patients administered the combination therapy had a 6.5 mm Hg greater reduction in mean systolic BP compared with the monotherapy groups, 25.3 mm Hg versus 18.9 mm Hg, respectively.
During weeks 16 to 32, all patients were placed on a combination therapy of 300 mg of aliskiren plus 10 mg amlodipine. At 24 weeks, researchers reported that the mean systolic BP difference was 1.4 mm Hg: 27.4 mm Hg for the initial combination therapy group versus 25.9 mm Hg across the monotherapy groups.
“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,” the researchers commented.
Brown and colleagues also reported the mean adjusted reduction in diastolic BP from baseline over weeks eight to 24 to be 12.4 mm Hg from the combination therapy group versus 8.7 mm Hg for patients in the monotherapy groups—a difference of 3.7 mm Hg. They noted that the initial combination therapy was more effective than both individual monotherapies in reducing BP rates.
The results of the initial combination in the second half of the study adjusted reductions of 27.4 mm Hg at 24 weeks and 26.4 mm Hg at 32 weeks was no greater than the sequential of aliskiren and then amlodipine. However, this was numerically superior to sequential amlodipine and then aliskiren, where the reductions were 25.5 mm Hg at 24 weeks and 24.3 mm Hg at 32 weeks.
In addition, adverse events caused 14 percent of patients from the combination group to withdrawal. Fourteen percent of patients from the aliskiren group and 18 percent from the amlodipine group also withdrew from the trial due to adverse events including peripheral oedema, hypotension or orthostatic hypotension.
While previous trials have studied the effectiveness of initial combination therapy with monotherapy, the results have always been short term, the authors noted. The current ACCELERATE study is the first to test the medium-term efficacy and safety of the two antihypertensive drugs as a first-line treatment for patients with a systolic BP of more than 150 mm Hg.
Over the six-month study period, patients administered the initial combination therapy achieved “superior reduction of blood pressure and tolerability, and can be advocated as the preferable treatment strategy to the convention of starting with one drug before the other.
“Both the larger early and smaller sustained superiority of combination therapy will probably influence guidelines,” Brown and colleagues wrote. “Meanwhile, physicians will note that their current first-choice drug, amlodipine, achieves lower blood pressures, and almost half the risk of severe ankle oedema, if started in combination rather than alone.
“A move towards routine initial reduction of blood pressure with combination therapy can now be advocated,” the researchers concluded.
The study was funded by Novartis Pharma.