Aliskiren

Oral renin inhibitor approved as monotherapy or in combination with other antihypertensive agents for the treatment of hypertension

Key Points

Tekturna Aliskiren NOVARTIS Oral renin inhibitor approved as monotherapy or in combination with other antihypertensive agents for the treatment of hypertension

This orally active, nonpeptide, direct renin inhibitor disrupts the renin-angiotensinaldosterone system by decreasing plasma renin activity and inhibiting the conversion of angiotensinogen to angiotensin I. Aliskiren was approved on March 5, 2007, for the treatment of hypertension, either alone or in combination with other antihypertensive agents.

Efficacy. The efficacy of aliskiren monotherapy was evaluated in 6 randomized, doubleblind, placebo-controlled, 8-week clinical trials in patients with mild-to-moderate hypertension. Approximately 2,730 patients were treated with aliskiren (75–600 mg), and approximately 1,231 patients were administered placebo. All 6 studies demonstrated significant reductions in seated trough cuff blood pressure for patients treated with aliskiren 300 mg versus those treated with placebo, with most of the studies also demonstrating a significant reduction in this measurement with aliskiren 150 mg. No clear further reduction was observed with aliskiren 600 mg. A high proportion (85%–90%) of aliskiren's effect on blood pressure was observed within 2 weeks of treatment. Patients enrolled in these trials were then treated with open-label aliskiren for ≤1 year; they then entered a randomized withdrawal study, which demonstrated a statistically significant difference between aliskiren-treated and placebo-treated patients. When treatment was stopped, blood pressure levels returned gradually (over a period of several weeks) to pretreatment, baseline levels. Aliskiren 75-, 150-, and 300-mg doses and hydrochlorothiazide 6.25-, 12.5-, and 25-mg doses were also studied alone and in combination in an 8-week, randomized, double-blind, placebo-controlled, parallel-group, 15-arm factorial study in 2,776 patients. Combination therapy resulted in greater blood pressure reductions than the reductions observed with either monotherapy. Similarly, combination therapy was more effective than monotherapy in lowering blood pressure when aliskiren 150-and 300-mg doses and valsartan 160-and 320-mg doses were studied alone and in combination in an 8-week, randomized, double-blind, placebo-controlled, parallel-group, 4-arm, dose-escalation study in 1,797 patients.

Dosing. The recommended starting dose of aliskiren is 150 mg once daily; if this regimen does not adequately control blood pressure, the dosage may be increased to 300 mg once daily. This agent may also be administered at the same dosage with other antihypertensive agents.