Additive Blood Pressure Reduction with Novel Direct Renin Inhibitor plus Valsartan

A significant additional blood pressure reduction was obtained with the combination of aliskiren and valsartan, compared to either drug alone, in the first large-scale study to evaluate the effects of dual renin system blockade. The patients had Stage 1 and Stage 2 hypertension. The results were presented by Dr. Suzanne Oparil, of the University of Alabama at Birmingham School of Medicine and lead investigator, at the 56th Annual Scientific Sessions of the American College of Cardiology, held in New Orleans from March 24-27, 2007.

Oparil stated that “aliskiren and valsartan are both effective antihypertensives, but they function very differently. Marrying these two treatment options will give physicians a more effective way to control high blood pressure in their patients.”

In the double-blind, placebo-controlled study, 1797 patients were randomized to one of four treatment arms: the combination of aliskiren 150 mg plus valsartan 160 mg, aliskiren 150 mg, valsartan 160 mg, or placebo for 4 weeks, and then the doses were doubled (to their maximum recommended doses) for an additional 4 week observation period. A washout period of 1 to 2 weeks was followed by a 3 to 4 week single-blind placebo-run in before the initial 4-week observation period. Blood pressure was measured at baseline, 4 weeks, and 8 weeks. In a subgroup of patients, 24-hour ambulatory blood pressure monitoring (ABPM) was performed at baseline and 8 weeks.

At 8 weeks, 49.3% of patients in the combination group had achieved blood pressure control of 140/90 mmHg, compared to 37.4% in the aliskiren group, 33.8% in the valsartan group, and 16.5% in the placebo group. ABPM showed greater blood pressure reductions with the combination compared to either drug alone.

Other key findings in this trial were:

Oparil stated that possible advantages for this “innovative drug” are biochemical, positive effects on target organ damage (studies under design) because of its blockage of Angiotensin II, and improved blood pressure reduction. Further, the drug class appears to be “clean”, she stated, without serious adverse event rates in more than 6000 patients studied to date. The most frequent side effect was headache, which was higher in the placebo group, which had a 36.7% rate of adverse events, compared to 34.1% for the combination of aliskiren plus valsartan and aliskiren alone, a rate similar to that with valsartan alone.

“Aliskiren is advantageous as a combination drug for hypertension,” stated Oparil, and that it may be particularly advantageous in the setting of diabetes, obesity, and hypertension requiring combination therapy, and that it will not have untoward effects of a diuretic.

Note from Website Editor Peter Nilsson, M.D., Department of Clinical Sciences Medicine University Hospital, Sweden:

"It is very promising that a new antihypertensive drug, aliskiren, has recently been approved by the FDA for clinical use. In the new study presented at the ACC it was compared to valsartan, but comparative studies with thiazide diuretics are also needed. All new cardiovascular drugs have to be tested against conventional drugs for clinical efficacy, but also the combination of a new drug with a conventional drug is worthy of investigation"