Combining Aliskiren ( Rasilez / Tekturna ) with Valsartan ( Diovan / Tareg ) at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent alone in patients with hypertension.
However, an accompanying comment author has raised concerns about potentially life threatening side effects.

The aim of this study was to assess dual renin system intervention with the maximum recommended doses of Aliskiren and Valsartan, compared with each drug alone in patients with high blood pressure.

In this double-blind study, 1797 patients with hypertension ( mean sitting diastolic blood pressure 95–109 mmHg and 8-h daytime ambulatory diastolic blood pressure =90 mmHg ) were randomly assigned to receive once-daily Aliskiren 150 mg ( n=437 ), Valsartan 160 mg ( 455 ), a combination of Aliskiren 150 mg and Valsartan 160 mg ( 446 ), or placebo ( 459 ) for 4 weeks, followed by forced titration to double the dose to the maximum recommended dose for another 4 weeks.

The primary endpoint was change in mean sitting diastolic blood pressure from baseline to week 8 endpoint.

A total of 196 ( 11% ) patients discontinued study treatment before the end of the trial ( 63 in the placebo group, 53 in the Aliskiren group, 43 in the Valsartan group, and 37 in the Aliskiren/Valsartan group ), mainly due to lack of therapeutic effect.

At week 8 endpoint, the combination of Aliskiren 300 mg and Valsartan 320 mg lowered mean sitting diastolic blood pressure from baseline by 12.2 mmHg, significantly more than either monotherapy ( Aliskiren 300 mg 9.0 mmHg decrease, p<0·0001; Valsartan 320 mg, 9.7 mmHg decrease, p<0·0001 ), or with placebo ( 4.1 mmHg decrease, p<0·0001 ).

Rates of adverse events and laboratory abnormalities were similar in all groups.

According to Authors, the combination of Aliskiren and Valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension.

In an accompanying comment, Willem H Birkenhäger, of Erasmus University in Rotterdam in Holland, and Jan A Staessen, of the University of Leuven in Belgium, cautioned that the proportion of patients with a transient increase of serum potassium above 5.5 mmol/L suggests a risk of hyperkalemia.

High potassium levels can cause severe complications, such as paralysis, arrhythmias, and cardiac arrest, and often remains unrecognized, with few symptoms prior to cardiac arrest.

According to editorialists, dual renin inhibition might find a niche in selected hypertensive patients at high risk with associated conditions or in treatment-resistant hypertension.

“ However, because of the 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," Birkenhäger and Staessen, wrote.

Source: The Lancet, 2007

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