New drug approved for treating hypertension

April 2, 2007

Aliskiren (Tekturna, Novartis) is a new molecular entity approved for treating hypertension either as monotherapy or in conjunction with other antihypertensive agents.

Nearly one in three American adults has high blood pressure, the "silent killer" that contributes substantially to heart failure, aneurysms, kidney failure, heart attacks, and strokes. Lifestyle modifications such as smoking cessation, reducing alcohol intake, losing weight, and dietary changes may reduce blood pressure slightly, but treatment with drugs is the only way to achieve major blood pressure reductions. Even with the numerous antihypertensives available, 70% of patients do not reach their blood pressure goals.

Although acting on the same pathway as ACE inhibitors, angiotensin receptor blockers (ARBs), and aldosterone receptor antagonists, aliskiren acts on the initial step of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct inhibitor of renin.

With cessation of therapy, blood pressure gradually returned to baseline over a period of several weeks, with no evidence of rebound hypertension. Despite aliskiren's antihypertensive efficacy, Wright pointed out, "The major goal of antihypertensive therapy is to prevent complications. We don't yet know the efficacy of Tekturna for end points such as heart failure and kidney protection."

More than 6,460 patients have been evaluated in studies to assess the safety of aliskiren. The most common side effect associated with the drug during clinical studies was diarrhea-an effect that appears to be more common in women and the elderly, especially at higher dosages of the drug. "Even though diarrhea was reported at an incidence of 2%, the drug was still very tolerable," remarked Wright.

Similar to other drugs acting on the RAAS, aliskiren was associated with a slight increase in cough, but it was substantially less than that resulting from use of an ACE inhibitor. The incidence of elevated uric acid, gout, and renal stones was also increased with aliskiren compared with placebo.

One-fourth of aliskiren is eliminated unchanged in the urine, but CYP 3A4 appears to be involved with the drug's metabolism, too. As a result, increased levels of aliskiren could be possible when used concomitantly with potent CYP P450 inhibitors such as ketoconazole. Additionally, blood levels of furosemide were significantly reduced when aliskiren was administered. This means that patients could find the therapeutic efficacy of furosemide diminished after beginning therapy with aliskiren.

According to Decision Resources, a leading research and advisory firm for pharmaceutical and healthcare issues, aliskiren is predicted to achieve blockbuster status, earning $2.1 billion over the next seven years. However, Wright, who runs a medication therapeutic management clinic at the VA medical center in Wilkes-Barre, Pa., believes in a wait-and-see approach. "I don't think aliskiren should be used early on in hypertension," he said. "We have many safe, proven, once-daily, less expensive alternatives already available. We don't know aliskiren's efficacy as far as reductions in end points and we don't know the long-term side effects."