Two Drug Therapy Recommended for Hypertension


The most effective way to reduce blood pressure in hypertensive patients is the use of a combination of drugs rather than one single drug, according to a study published in the Lancet today.

Prof Morris J Brown, Addenbrooke's Hospital, Cambridge and University of Cambridge, UK, and colleagues conducted a double-blind, randomised, parallel-group, superiority trial (ACCELERATE) at 146 primary and secondary care sites in ten countries, with enrolment from Nov 28, 2008, to July 15, 2009.

Patients eligible for enrolment had essential hypertension, were aged 18 years or older, and had systolic blood pressure between 150 and 180 mm Hg.

The researchers state ACCELERATE is the first trial to test the medium-term efficacy and safety of full doses of two antihypertensive drugs as first-line treatment for patients with a systolic blood pressure greater than 150 mm Hg, by comparison with sequential add-on treatment with the same drugs.

Patients were randomly assigned (1:1:2) to treatment with 150 mg aliskiren plus placebo (n=315), 5 mg amlodipine plus placebo (n=315), or 150 mg aliskiren plus 5 mg amlodipine for treatment the first 16 weeks (n=617). 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 (ie, in patients who received the allocated treatment), were the adjusted mean reduction in systolic blood pressure from baseline over 8 to 24 weeks, and then the final reduction at 24 weeks.


Patients given initial combination therapy had a 6·5 mm Hg (95% CI 5·3 to 7·7) greater reduction in mean systolic blood pressure than the monotherapy groups (p

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. These adverse events were peripheral edema, hypotension, or orthostatic hypotension.

The British Heart Association’s associate medical director, Professor Jeremy Pearson, said: “This study adds significantly to the evidence that starting treatment for patients with high blood pressure with two medicines rather than one is safe, and more effective than waiting to add the second medicine later.

Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Aliskiren is the first drug to inhibit renin directly.

Amlodipine is a long-acting calcium channel blocker (dihydropyridine class) used as an anti-hypertensive and in the treatment of angina. Like other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance and hence reducing blood pressure, while in angina it increases blood flow to the heart muscle.

The study was funded by Novartis Pharma AG.

Aliskiren and the calcium channel blocker amlodipine combination as an initial treatment strategy for hypertension control (ACCELERATE): a randomised, parallel-group trial; Prof Morris J Brown FMedSci,Prof Gordon T McInnes FRCP,Cheraz Cherif Papst PhD,Jack Zhang MD,Prof Thomas M MacDonald FRCP; The Lancet - 13 January 2011
DOI: 10.1016/S0140-6736(10)62003-X