High Dose Combination Therapy Better Than Monotherapy For Lowering Hypertension

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Main Category: Hypertension
Also Included In: Cardiovascular / Cardiology;  Clinical Trials / Drug Trials
Article Date: 20 Jul 2007 - 0:00 PDT

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Patients with hypertension who receive aliskiren in combination with valsartan at the highest recommended doses experience much greater reductions in blood pressure, compared to monotherapy with either drug. The combined therapy's tolerability profile is similar to the monotherapy's with either drug.

You can read about this in The Lancet, this week's issue. A comment which accompanies the article says that it is doubtful this will ever make it into general practice or primary prevention in specialist care because of the potentially fatal side-effects of high blood potassium.

Aliskiren and valsartan work by reducing the amount of rennin in the kidneys. Renin raises blood pressure by constricting the blood vessels - it is a vasoconstricting substance. By inhibiting the rennin system of the kidneys, these drugs lower the blood pressure of people who suffer from hypertension (high blood pressure).

Prof. Suzanne Oparil, University of Birmingham, and team, carried out a study of 1,797 patients who suffered from hypertension. They were divided into four groups:

-- One group received daily aliskiren 150 mg (monotherapy aliskiren group)
-- One group received daily valsartan 160 mg (monotherapy valsartan group)
-- One group received a daily combination of aliskiren 150 mg and valsartan 160 mg (combination therapy group)
-- One group received a daily placebo (placebo group)

The treatment was for four weeks in each group, followed by another four weeks on the maximum recommended dose(s). 196 patients dropped out before the trial ended - these numbers were evenly spread across the four groups. The main reason the placebo group people dropped out was because they were experiencing no therapeutic effect - a much smaller proportion dropped out of the other groups for the same reason.

The combination therapy group on maximum doses experienced a mean drop in their sitting diastolic blood pressure of 12.2 mm Hg, compared with 9.0 mm Hg for the monotherapy aliskiren group and 9.7 mm Hg for the monotherapy valsartan group.

Rates of laboratory abnormalities and adverse events were pretty similar across the four groups.

"These findings provide a clear rationale for further studies to investigate the potential effects of long-term treatment with the combination of aliskiren and valsartan, and combinations of aliskiren with other angiotensin receptor blockers, on possible benefits beyond treating hypertension," the authors concluded.

The accompanying comment, by Dr Willem Birkenhäger, Rotterdam, Netherlands, and Dr Jan Staessen, University of Leuven, Belgium, explained that a higher proportion of patients in the combination therapy group experienced transient increases in serum potassium to about 5.5 mmol/l - higher than the other groups. Serum potassium levels greater than 6.0 mmol/l (hyperkalaemia) can cause paralysis, arrhythmias, and cardiac arrest. They added that severe hyperkalaemia is often undetected, as it has few symptoms prior to cardiac arrest. "Because of potential life-threatening side effects, which require biochemical monitoring, this concept of treatment is unlikely to make it to general practice or even to primary prevention in specialist care," they concluded.

http://www.thelancet.com

Written by: Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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