New renin inhibitor provides further BP reduction when added to ARB

March 26, 2007

The recently approved renin inhibitor aliskiren used in combination with the angiotensin receptor blocker (ARB) valsartan results in an improved blood pressure (BP) response, compared with the use of either agent alone, said Suzanne Oparil, MD, at the American College of Cardiology's 56th annual scientific session.

The recently approved renin inhibitor aliskiren used in combination with the angiotensin receptor blocker (ARB) valsartan results in an improved blood pressure (BP) response, compared with the use of either agent alone, said Suzanne Oparil, MD (pictured left), at the American College of Cardiology's 56th annual scientific session.

Aliskiren represents a drug from the first new class of antihypertensive agents since 1994. It works by blocking renin at its rate-limiting (first) step, whereas ACE inhibitors and ARBs block the renin angiotensin system (RAS) downstream, Dr. Oparil said. Furthermore, ACE inhibitors and ARBs are associated with a compensatory increase in renin release and plasma renin activity, as a result of blocking the RAS.

Combining aliskiren with an ARB would be expected to block the compensatory rise in plasma renin activity observed with an ARB alone. Therefore, combining the two is logical in an attempt to lower BP, according to Dr. Oparil.

Dr. Oparil reported the results of a randomized, double-blind, placebo-controlled study of 1,797 patients with mild to moderate hypertension, defined as a resting diastolic blood pressure (DBP) of 95 to

Valsartan was started at 160 mg/d and titrated up to 320 mg/d at week 4; aliskiren was started at 150 mg/d and titrated to 300 mg/d at week 4. Total treatment duration was 8 weeks.

"We used maximum doses of both drugs, and found additive blood pressure effects and no additional adverse events," said Dr. Oparil, director of the University of Alabama-Birmingham Vascular Biology and Hypertension Program.

The primary endpoint, sitting DBP at week 8, was decreased by 4.1 mm Hg in the placebo arm, 9.0 mm Hg in the aliskiren monotherapy arm, 9.7 mm Hg in the valsartan monotherapy arm, and 12.2 mm Hg in the combined aliskiren/valsartan arm.

Blood pressure control, defined as achievement of blood pressure to

Plasma renin activity was increased by 160% with valsartan alone. With the combination of aliskiren and valsartan, plasma renin activity dropped by 44%.

If the RAS can be more completely inhibited by adding aliskiren to an ARB, "formation of angiotensin II will dwindle, and will reduce the proinflammatory effects and pro-oxidative effects of this nasty little peptide," Dr. Oparil said.