Analysis: New Paradigm for Blood Pressure?

By ED SUSMAN

Researchers said Wednesday that a drug being reviewed for approval by the Food and Drug Administration not only dramatically reduces blood pressure but smoothes out daily pressure to avoid dangerous variability in the morning and evening.

Aliskerin is the first oral direct renin inhibitor and has the potential to protect the heart and other organs by continuous, smooth blood pressure lowering, said Jerry Mitchell, chairman of the Texas Center for Drug Development, a Houston-based research company.

In several studies being presented at the 21st annual scientific meeting of the American Society of Hypertension in New York, Mitchell said that the drug, being developed by Novartis, is able to keep blood pressures low because it has a long half life — more than 40 hours — that allows it to be dosed once a day. The company filed in February for FDA approval.

For decades scientists have tried to develop a direct renin inhibitor for treatment of high blood pressure, but previous attempts could only be used as intravenous infusions and they were effective only for a few minutes, Steven Zelenkofske, senior medical director for the aliskerin project for Novartis, told United Press International.

This new drug is a breakthrough. It binds tightly to renin and appears to continue to work even when the drug is gone from the blood stream, Zelenkofske said. It is ideal for once-daily dosing. There is no apparent buildup in the body.

By directly inhibiting the action of renin, aliskerin prevents the molecular cascade that is involving in raising blood pressure. High blood pressure is implicated in heart attacks, strokes and kidney failure.

In Mitchell’s study 672 patients were treated with either a placebo or three different doses of aliskerin, 150 mg, 300 mg or 600 mg. About one-third of each group was then given 24-hour blood-pressure monitors to carry in attempts to see how the drug reacts all day long.

He said blood-pressure control was maintained virtually the entire day with the 300 mg dose; a dose he said he believes will be the one doctors are likely to select in treating patients with high blood pressure once the pill is available.

Blood pressure varies all day long, said Kenichi Sakakura, a staff physician at the Public Kiwa clinic in Kumano City, Japan. What we want to do it to prevent blood pressure from varying excessively and outside the normal range.

Sakakura investigated blood-pressure variability in the elderly, concluding that greater variability adversely effects cognition in these individuals. He told UPI that a long-lasting, effective medication is needed to maintain blood pressure within normal ranges. He suggested that aliskerin when approved appears to be a drug that can accomplish that task.

In another study — presented at a news briefing along with Sakakura’s and Mitchell’s work — Alberto Villamil, president of the cardiovascular research clinic Fundapres in Buenos Aires, said that combining aliskerin with a diuretic allowed doctors to provide blood-pressure control to up to 80 percent of patients.

In the United States today about 30 percent of patients have their high blood pressure under control, and that is considered the best record in blood-pressure control in the world.

Villamil enrolled 2,776 patients in a study that compared aliskerin to the diuretic to placebo and to the combination. Overall, there were 15 different treatment arms in the study. At the start of the study, 45 percent of patients with mild to moderate high blood pressure who were given the placebo were able to keep their blood pressure under control, compared with 80.6 percent of patients on the combination of 300 mg aliskerin and 12.5 mg of diuretics.

In combination with diuretics, aliskerin provides significant additional blood pressure reductions, Villamil said.