Novel BP Agent Shows Clinical Promise
Aliskiren suppresses plasma renin activity even when other BP medications stimulate renin
CHICAGO—Aliskiren, the first in a new class of direct renin inhibitors, is a useful adjunct to other antihypertensive agents for patients with mild to moderate hypertension, data suggest.
The drug suppresses plasma renin activity (PRA) even when renin secretion is strongly stimulated by other antihypertensive agents.
Researchers analyzed pooled data from four randomized, double-blind trials of aliskiren, which targets the renin system at a different site than ACE inhibitors and angiotensin receptor blockers. The trials included a total of 4,937 patients with a mean systolic BP of 153.8 mm Hg and a mean diastolic BP of 99.1 mm Hg.
Alan H. Gradman, MD, chief of the division of cardiovascular diseases at Western Pennsylvania Hospital in Pittsburgh, presented findings at the American Heart Association 2006 Scientific Sessions here. He explained that both ACE inhibitors and ARBs increase PRA by disrupting feedback inhibition of renin release from the kidney. Aliskiren reduces PRA, thereby blocking synthesis of angiotensin I and II.
The four studies were aliskiren/ irbesartan versus placebo; aliskiren versus placebo; aliskiren versus hydrochlorothiazide versus aliskiren/hydrochlorothiazide versus placebo; and aliskiren versus ramipril versus aliskiren/ramipril. Mean PRA levels at baseline across the whole study population were 0.43-0.65 ng/mL/h. Aliskiren monotherapy at a dosage of 150-600 mg once daily achieved highly significant PRA reductions (greater than 70%) compared with placebo, despite dose-dependent increases in renin concentration.
The other drugs used in the trials significantly increased renin concentrations. When aliskiren was combined with hydrochlorothiazide or ramipril, renin release increased but PRA was suppressed by aliskiren. Reductions in PRA in combination therapy were similar to those observed with monotherapy. The tolerability profile of aliskiren in these trials was similar to that of placebo, Dr. Gradman said.