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Major UK trial backs routine use of combination treatment for hypertension

By Christian Duffin

Momentum is growing for a major overhaul of guidance on the management of patients with hypertension, after UK researchers unveiled the latest trial to show that initial combination therapy achieves substantially better blood pressure reduction than monotherapy.

The ACCELERATE trial - led by a former president of the British Hypertension Society - showed a combination of amlodipine and aliskiren, when used as first-line treatment for patients with a systolic blood pressure greater than 150mm Hg, achieved a 6.5mm Hg greater reduction in mean systolic blood pressure when compared with sequential treatment with the same drugs.

Sequential use of drugs has been the mainstay of hypertension management since the publication of the ABCD treatment algorithm in the NICE guidance on hypertension, published in 2006.

But as Pulse first revealed in May, experts at the Joint British Societies are considering how to introduce the use of combination therapies ‘much earlier in the treatment algorithm', in what we be major shake-up of current practice designed to promote rapid and aggressive blood-pressure control. Currently combination antihypertensives account for less than 1% of all prescriptions.

Experts have been awaiting the results of late-stage clinical trials of antihypertensive combinations to provide the evidence for the JBS3 committee to rewrite its guidance, due out in the spring.

The ACCELERATE trial randomised 634 patients in ten countries with a systolic blood pressure between 150 and 180mm Hg to treatment with 150mg aliskiren plus placebo, 5mg amlodipine plus placebo or 150mg aliskiren plus 5mg amlodipine. From 16-32 weeks, all patients received combination therapy with 300mg aliskiren plus 10mg amlodipine.

In a comparison of weeks eight to 24 with baseline, patients given initial combination therapy had a 6.5mm Hg greater mean adjusted reduction in systolic blood pressure than the monotherapy groups. At 24 weeks, when all patients were on combination treatment, mean blood pressure in the monotherapy group fell towards, but did not catch up with, the combination group, but was still 1.4 mm Hg higher.

The research was funded by Novartis, manufacturers of both aliskiren and an amlodipine-containing antihypertensive. Aliskiren is a renin inhibitor, and Pulse had revealed the JBS3 guidance may also contain a recommendation to encourage GPs to use renin testing to guide treatment for patients with resistant hypertension

Professor Morris Brown, professor of clinical pharmacology at the University of Cambridge led the research, published online in The Lancet last week. He concluded: ‘We believe that routine initial reduction in blood pressure higher than 150 mm Hg with a combination such as aliskiren plus amlodipine can be recommended.'

Professor Brown, professor of clinical pharmacology at the University of Cambridge, said: ‘There has been concern about side effects from combination therapy but this trial puts that to rest. There is no reason now not to start treatment with two drugs.'

Major UK trial backs routine use of combination treatment for hypertension


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