March 17, 2006

Charlene Laino

March 17, 2006 (Atlanta) — Aliskiren, the first in a new class of orally administered renin inhibitors, is superior to placebo in lowering blood pressure in patients with mild to moderate hypertension, a phase 2 study suggests.

In a randomized, double-blind, placebo-controlled, 8-week study of 672 patients, the proportion of participants who experienced a more than 10 mm Hg reduction in diastolic blood pressure and/or a diastolic blood pressure reading of less than 90 mm Hg was significantly higher in patients receiving aliskiren, 150 mg (59%), 300 mg (63%), or 600 mg (69%), compared with those receiving placebo (36%).

"All the differences were highly significant, with a P value of less than .0001," said chief investigator Byung-Hee Oh, MD, from Seoul National University College of Medicine in South Korea.

"Importantly, there was sustained and consistent blood pressure lowering throughout the 24-hour dosing interval," Dr. Oh told Medscape. "This is important because blood pressure fluctuates over a 24-hour period, and most myocardial infarctions and other serious cardiac events occur in the morning."

Aliskiren targets the renin-angiotensin-aldosterone pathway that is central to blood pressure control, Dr. Oh said. He presented the findings here at the American College of Cardiology (ACC) 55th Annual Scientific Session.

In the study, patients with mild to moderate hypertension, defined as a resting diastolic blood pressure (DBP) of 95 to 110 mm Hg, were randomized to 150 mg (n = 172), 300 mg (n = 169), or 600 mg (n = 166) of aliskiren or placebo (n=165), once daily for 8 weeks.

After 8 weeks of treatment, both diastolic and systolic blood pressure decreased significantly more in patients receiving aliskiren than in those receiving placebo. Patients receiving placebo experienced a blood pressure decrease of 4.9/3.8 mm Hg compared with a 10.3/13.0 mm Hg reduction in those receiving 150 mg of aliskiren, an 11.1/14.7 mm Hg decreased in those receiving 300-mg dose, and a 12.5/15.8 mm Hg decrease in blood pressure in patients receiving 600 mg of aliskiren.

Aliskiren was generally well tolerated, with the overall rate of adverse events ranging from 40.1% to 52.4% compared with 43.0% in the placebo group.

At the 600-mg dose, patients experienced a greater incidence of diarrhea: 11.4% compared with 1.2% to 1.8% among patients receiving lower doses or placebo. But Dr. Oh said that the symptoms were mild, and only 1 patient in this group and 1 patient in the placebo group dropped out of the study due to diarrhea.

James H. Stein, MD, cochair of the scientific program committee for the ACC meeting and associate professor of medicine at the University of Wisconsin Medical School in Madison, said that aliskiren has the potential to be an important new treatment for blood pressure lowering, but long-term studies are still needed.

"Although we have many drugs to treat high blood pressure, the majority of the 65 million Americans with hypertension are not controlled," Dr. Stein told Medscape. "And among those who are controlled, many are on 2 or more medications. There is always room for new medications like this."

The drug is being developed by Novartis Pharmaceuticals, which funded the study.

ACC 55th Annual Scientific Session: Abstract 1027-191. Presented March 14, 2006

Reviewed by Ariana Del Negro

Charlene Laino is a freelance writer for Medscape.