BARCELONA — Aliskiren, the first drug from a new class of orally active, direct renin inhibitors, was safe and effective for lowering blood pressure in more than 7,000 patients who were enrolled in seven randomized, controlled trials.
Perhaps the most notable finding from this combined analysis was the new drug's safety. During 6–8 weeks of daily treatment with aliskiren, patients in these studies had adverse effect profiles similar to those of the placebo arms, with fewer than 1% of patients having a serious adverse effect or withdrawing from treatment because of adverse effects, Dr. Matthew R. Weir said at a joint meeting of the European Society of Cardiology and the World Heart Federation.
The trial results also showed that treatment with aliskiren led to incremental reductions in diastolic blood pressure in patients who were already treated with an ACE inhibitor (ramipril), a calcium-channel blocker (amlodipine), or a thiazide diuretic. Aliskiren failed to produce additional blood pressure lowering when it was added to an angiotensin-receptor blocker (valsartan). This last result needs to be confirmed in a new study, said Dr. Weir, professor of medicine and chief of the division of nephrology at the University of Maryland in Baltimore.
Aliskiren dosages in the studies ranged from 75 to 600 mg/day. The drug was tested as monotherapy and was compared with placebo in five studies, and it was tested in combination therapy against active controls in two studies.
Patients enrolled in the seven studies had blood pressures at baseline of about 100 mm Hg diastolic and 151–157 mm Hg systolic. After 6–8 weeks of treatment with aliskiren, diastolic pressure fell by an average of 7–8 mm Hg, and systolic pressure fell by an average of 10–11 mm Hg. The effect of aliskiren on blood pressure reduction was dose-dependent, with a plateau reached once the dosage was 300–600 mg/day. The age and gender of patients appeared to have no effect on the degree of blood pressure reduction.
Aliskiren is being developed by Novartis. The company submitted an application to the Food and Drug Administration last April to market the drug as an antihypertensive. Once approved, aliskiren will be marketed as Rasilez. All seven studies included in the analysis were sponsored by Novartis, and Dr. Weir has received honoraria from Novartis.
Once the drug is available, it will be a good choice for both initial therapy and in combination with other antihypertensive drugs, he said. Aliskiren would be an attractive first-line agent given its good safety profile and low rate of interactions with other drugs.
“The major question is whether inhibiting the renin-angiotensin system [with aliskiren] gives us an opportunity to better protect blood vessels and target organs,” Dr. Weir said. Studies designed to address this issue are now in progress.