Valsartan and aliskiren (Valturna): Combination of an angiotensin receptor blocker with direct renin inhibitor approved for the treatment of hypertension

New combination: Valturna was approved on September 16, 2009, for the treatment of hypertension in patients not adequately controlled on either aliskiren or angiotensin receptor blocker monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

Valsartan-aliskiren targets the renin angiotensin aldosterone system (RAAS) in two ways. Valsartan blocks at the receptor the action of angiotensin II, an important end product of the RAAS that causes blood vessels to tighten and narrow. Aliskiren reduces angiotensin II levels by directly inhibiting renin, an enzyme produced by the kidneys that starts a process that leads to the formation of angiotensin II. By targeting two key points within the RAAS, valsartan-aliskiren helps blood vessels relax and widen thereby lowering blood pressure. Valturna was approved on September 16, 2009, for the treatment of hypertension in patients not adequately controlled on either aliskiren or angiotensin receptor blocker monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

Efficacy. Valsartan-aliskiren's approval was based primarily on an 8-week randomized, double-blind, placebo-controlled clinical trial of about 1,800 patients, which studied aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. Initially, the doses of aliskiren and valsartan were 150 mg and 160 mg, respectively, and were increased at 4 weeks to 300 mg and 320 mg, respectively. Blood pressure reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the 8-week primary endpoint. Mean systolic and diastolic blood pressure reductions from baseline were 17.2/12.2 mm Hg for aliskiren 300 mg/valsartan 320 mg, compared with 12.8/9.7 mm Hg for valsartan 320 mg, 13.0/9.0 mm Hg for aliskiren 300 mg, and 4.6/4.1 mm Hg for placebo (P<0.05 for aliskiren/valsartan versus monotherapies or placebo).

Safety. Valsartan-aliskiren may cause fetal injury and death and pregnant patients should discontinue taking it as soon as possible. Nursing mothers should either stop nursing or discontinue taking valsartan-aliskiren. The most common adverse events (incidence > 1.5% and more common than placebo) were fatigue and nasopharyngitis. Valsartan-aliskiren should be discontinued in patients with head and neck angioedema until symptoms resolve. To avoid hypotension in volume-or salt-depleted patients, imbalances should be corrected before initiating therapy. For patients with renal impairment, decreases in renal function may be anticipated in susceptible individuals. Slower clearance may occur in patients with hepatic impairment. To avoid hyperkalemia, consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances, particularly in patients at risk. Concomitant use with cyclosporine is not recommended. Use with potassium-sparing diuretics, potassium supplements or salt substitutes may lead to increases in serum potassium, and in heart failure patients, increases in serum creatinine.