NEW YORK — A new oral antihypertensive drug, the renin inhibitor aliskiren, was effective when given with a diuretic, and it also achieved consistent, 24-hour blood pressure control as monotherapy in a pair of studies that together included about 3,000 patients.

The successful pairing of aliskiren with the diuretic hydrochlorothiazide was seen as a step forward for this agent—the first from a novel drug class—because it showed evidence of blocking renin, the rate-limiting enzyme of the renin-angiotensin-aldosterone system. Water depletion by diuretics stimulates renin release from the kidneys, but the activity of this renin surge was effectively blunted by concurrent treatment with aliskiren, according to the combination study.

“It's a proof of principle,” Dr. George L. Bakris said in an interview at the annual meeting of the American Society of Hypertension. But despite the encouraging development, a much fuller picture of aliskiren will unfold over the next year as new data are reported on the drug's ability to exert additional effects, such as controlling heart failure.

The hope is that aliskiren and other renin inhibitors may prove as effective as agents from the other drug classes that inhibit the renin-angiotensin-aldosterone system—the ACE inhibitors and the angiotensin-receptor blockers, said Dr. Bakris, director of the Rush University Hypertension Center in Chicago.

Novartis AG, the company that makes aliskiren (Rasilez), has submitted a licensing application to the Food and Drug Administration for approval to market aliskiren for lowering blood pressure. A decision by the agency is expected in early 2007, said Dr. Steve Zelenkofske, senior medical director for the U.S. aliskiren program.

Clinical research data on aliskiren were first reported last March at the annual meeting of the American College of Cardiology from a study of 672 hypertensive patients who received aliskiren monotherapy.

Additional results from this trial, involving a subset of 216 patients who underwent ambulatory blood pressure monitoring, were reported in a poster at the American Society of Hypertension meeting by Dr. Jerry Mitchell, a researcher with the Texas Center for Drug Development in Houston.

The findings showed that once-daily treatment with aliskiren, which has a 40-hour serum half-life, led to “smooth blood pressure control” with no signs of blood pressure variability and “minimal loss of effect throughout 24 hours,” said Dr. Mitchell. “Blood pressure variability is associated with end-organ damage to the heart, kidney, and brain,” but aliskiren appeared effective at eliminating early-morning blood pressure surges, he said.

In the full study of 672 patients, treatment with aliskiren had a safety profile that was similar to the placebo-treated control group. This study was funded by Novartis; Dr. Mitchell reported no other financial relationship with the company.

Combination treatment with aliskiren and hydrochlorothiazide was assessed in a study of 2,776 patients in Argentina, reported Dr. Alberto S. Villamil in a second poster at the meeting. The study involved 15 different treatment groups: Aliskiren monotherapy was administered at dosages of 75, 150, or 300 mg/day, hydrochlorothiazide monotherapy was given at dosages of 6.25, 12.5, or 25 mg/day, and various combinations of both drugs at these dosages were also tested. The study also included a placebo group, and treatment was continued for 8 weeks. This study was also sponsored by Novartis; Dr. Villamil reported no other financial relationship with the company.

Aliskiren monotherapy lowered blood pressure in a dose-dependent way, with the 300-mg/day dosage producing an average 15.7-mm Hg drop in systolic pressure and a 10.3-mm Hg reduction in diastolic pressure after 8 weeks. This reduction compared with the 14.3/9.4-mm Hg decrease in pressure produced by the highest dose of hydrochlorothiazide monotherapy tested, and the 7.5/6.9-mm Hg average decline in the placebo-treated group.

Combination regimens of aliskiren and hydrochlorothiazide led to larger reductions in blood pressure than either drug alone. The biggest decline was produced by the highest dosage tested—300 mg aliskiren plus 25 mg hydrochlorothiazide—which led to an average pressure cut of 21.2/14.3-mm Hg, reported Dr. Villamil, president of Fundapres and chief of the hypertension section at Dr. Cosme Argerich Hospital in Buenos Aires.

Treatment-related adverse effects were reported in 12% of patients who received the highest dosage of aliskiren plus hydrochlorothiazide, compared with a 9% rate in the placebo group.

Perhaps the most intriguing result from this study was reported in a separate poster at the meeting by Dr. David Calhoun, a cardiologist at the University of Alabama, Birmingham. The researchers measured plasma renin levels and plasma renin activity in all participants at baseline and after 8 weeks of treatment.

Plasma renin concentrations rose from baseline in all patients, with the largest increases seen in patients who received both antihypertensive drugs. But the data also showed that aliskiren was effective at blocking renin activity (see chart).

Aliskiren Plus a Diuretic Controls 24-Hour Blood Pressure