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Two Drugs Better Than One In Lowering Blood Pressure

Date:
July 24, 2007
Source:
The Lancet
Summary:
The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent alone in patients with hypertension (high blood pressure), and the tolerability profile of the combined treatment is similar to the two-single agent treatments. The findings are reported in a recent article. However an accompanying comment warns that the potentially life-threatening side effect of high blood potassium makes the treatment unlikely to make it to general practice or even primary prevention in specialist care.
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The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent alone in patients with hypertension (high blood pressure), and the tolerability profile of the combined treatment is similar to the two-single agent treatments.

The findings are reported in an article in The Lancet. However an accompanying comment warns that the potentially life-threatening side effect of high blood potassium makes the treatment unlikely to make it to general practice or even primary prevention in specialist care.

Both aliskiren and valsartan are inhibitors of the renin system of the kidneys. Renin is a vasoconstricting substance (one which constricts the blood vessels and thus increases blood pressure), and thus inhibition of the renin system lowers blood pressure in individuals with high blood pressure.

Professor Suzanne Oparil, University of Birmingham, Alabama and colleagues did a study of 1797 patients with hypertension, who were divided into four groups. The first group received once-daily aliskiren 150mg, the second once daily valsartan 160mg, the third a combination of aliskiren 150mg and valsartan 160mg once daily, and the fourth a placebo. The treatment was given for four weeks, followed by four weeks of double doses in each of the four groups, which represented the maximum recommended dose.

A total of 196 patients, spread across the four groups, discontinued treatment before the end of the trial, with lack of therapeutic effect being the most common reason for discontinuation for placebo-treated patients and the least common for combination-treated patients.The researchers found that the group receiving the maximum doses of aliskiren and valsartan combined experienced a mean drop in their sitting diastolic blood pressure of 12.2mm Hg, compared to 9.0mm Hg decrease in the aliskiren group, 9.7mm Hg decrease in the valsartan group, and 4.1mm Hg decrease in the Placebo group. Rates of adverse events and laboratory abnormalities were similar in all groups.

The authors conclude: “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.”

In the accompanying comment, Dr Willem Birkenhäger, Rotterdam, Netherlands, and Dr Jan Staessen, University of Leuven, Belgium, point out that the proportion of patients with a transient increase in serum potassium to around 5.5mmol/l is higher in the combination treatment group than any other group, and that hyperkalaemia (serum potassium grater than 6.0mmol/l) can cause severe complications such as paralysis, arrhythmias, and cardiac arrest. Severe hyperkalaemia often remains unrecognised, with few symptoms prior to cardiac arrest.

The Comment authors conclude: “Because of potential life-threatening side effects, which require biochemical monitoring, this concept of treatment is unlikely to make to general practice or even to primary prevention in specialist care.”


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Materials provided by The Lancet. Note: Content may be edited for style and length.


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The Lancet. "Two Drugs Better Than One In Lowering Blood Pressure." ScienceDaily. ScienceDaily, 24 July 2007. <www.sciencedaily.com/releases/2007/07/070722204216.htm>.
The Lancet. (2007, July 24). Two Drugs Better Than One In Lowering Blood Pressure. ScienceDaily. Retrieved May 7, 2017 from www.sciencedaily.com/releases/2007/07/070722204216.htm
The Lancet. "Two Drugs Better Than One In Lowering Blood Pressure." ScienceDaily. www.sciencedaily.com/releases/2007/07/070722204216.htm (accessed May 7, 2017).