FDA approves renin inhibitor aliskiren for hypertension

The FDA approved aliskiren, the first hypertension treatment that inhibits renin.

Aliskiren (Tekturna, Novartis) is also the first, new type of hypertension drug approved by the FDA in more than a decade, according to company officials.

Aliskiren is a once-daily tablet (150 mg and 300 mg) indicated as monotherapy or in combination with other hypertension medications.

Franz Messerli, MD, director of the hypertension program in the division of cardiology at St. Luke’s-Roosevelt Hospital, Columbia University, New York, said he is skeptical about where aliskiren fits into the antihypertensive arsenal.

“Is there a need for triple blockade of the renin angiotensin system and if so, what is the risk-benefit ratio?” Messerli, section editor of the Hypertension and Vascular Disease section of Today in Cardiology, said. “As it is introduced now, I don’t see the exact place in the therapeutic arsenal.”

Approval basis

According to the FDA, researchers evaluated aliskiren’s effectiveness through six, placebo-controlled, eight-week clinical trials involving more than 2,000 patients with mild to moderate hypertension.

The antihypertensive effect was maintained for up to one year across all demographic subgroups; however, blacks tended to have smaller reductions in BP than whites and Asians. This is generally true for drugs that affect the renin-angiotensin system, according to the FDA.

Studies showed that when aliskiren was combined with hydrochlorothiazide, further BP reductions were noted.

Researchers evaluated the safety of aliskiren in more than 6,460 patients, including 1,740 who were treated longer than six months and more than 1,250 patients treated for longer than one year. The most common adverse event was diarrhea, which was reported by about 2% of patients assigned the 300-mg dose compared with 1% assigned placebo.

A rare adverse event was allergic swelling of the face, lips or tongue and difficulty breathing, side effects that are common with other drugs for hypertension that act directly on the renin-angiotensin system.

Angioedema was rarely reported in patients taking aliskiren, according to the company.

Where does it fit in?

Messerli said the drug may have distinct advantages in patients with diabetes. In these patients, pro-renin levels are related to microvascular complications and renin inhibitors may interfere with pro-renin signalling at the receptor.

“From a purely antihypertensive point of view, I can not perceive that a drug that has a very similar shallow dose response curve as the angiotensin receptor inhibitors but seems to have more adverse effects will confer a distinct advantage,” Messerli said. “One possible indication could be in patients who can not take ACE inhibitors because of cough or angioedema and need a double blockade of the renin angiotensin system, such as patients with diabetes and albuminuria.”

The questions he has may be answered in time, Messerli said.

“As you can see, there seem to be more questions than answers at the present time,” he said. “However, this is not unusual when a new compound is introduced, because our vision of efficacy and safety is still narrow because of a lack of data.”

Novartis warns that aliskiren should be discontinued as soon as pregnancy is detected because it can harm the fetus with injury or death. Physicians are advised to talk about other treatment options with women planning pregnancy.

The company plans a large outcome trial to evaluate the long-term effectiveness of aliskiren and direct renin inhibition, the company said.

“By inhibiting this important system at its origin, renin production, a direct renin inhibitor such as [aliskiren] offers an exciting therapeutic option for treating hypertension,” said Marc A. Pfeffer, MD, PhD, professor of medicine at Harvard Medical School and cardiologist at Brigham and Women’s Hospital, in a press release.