Hypertension affects approximately 70 million Americans and is a major risk factor for cardiovascular disease. It has been estimated that up to 65% of patients with hypertension do not have their blood pressure (BP) under control. Other studies have demonstrated that as many as 85% of hypertensive patients may need multiple medications to control their BP, underscoring the need for effective combination treatments.

In 2009, the FDA approved aliskiren/valsartan (Valturna, Novartis) as a single-pill combination for the treatment of high BP in patients not adequately controlled on aliskiren or valsartan monotherapy. It was also approved as initial therapy in patients likely to need multiple drugs to achieve BP goals. Aliskiren/valsartan targets two key points within the renin-angiotensin aldosterone system (RAAS), which is believed to be an important regulator of BP. Valsartan blocks the action of angiotensin II, a component of the RAAS that causes blood vessels to tighten and narrow. Aliskiren directly inhibits renin, an enzyme that initiates the processes that lead to formation of angiotensin II. By targeting these two points within the RAAS, the agent helps blood vessels relax and widen so BP is lowered.

Analyzing Clinical Trial Data

A pivotal 8-week randomized, double-blind, placebo-controlled clinical trial involving about 1,800 patients helped lead to the FDA’s approval of aliskiren/valsartan. This trial analyzed use of aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. Initial 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. BP reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the 8-week primary endpoint. Mean systolic/diastolic BP 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.

Patient Selection & Considerations

The aliskiren/valsartan combination offers a unique approach to blockade of the RAAS at two key points. Furthermore, patients with proteinuria or chronic kidney disease can experience greater reductions in proteinuria with this combination therapy than by using either compound alone. It should be noted, however, that surveillance to ensure that BP reductions occur within 4 weeks is recommended. When using aliskiren/valsartan, kidney function should be monitored, especially in those with renal impairment. Small reductions in kidney function may occur when the drug is initially used, but this impairment will stabilize over the long term. Hyperkalemia, particularly in patients with diabetes, should also be monitored. Clinicians should consider using a diuretic in patients at high risk for hyperkalemia to minimize risk of this complication. In pregnant women, the agent should be avoided because drugs that act directly on the RAAS can cause injury and death to the developing fetus.

A Welcome New Addition

There is a clear need for newer therapies that both lower BP and protect cardiovascular target organs. Unfortunately, achieving cardiovascular protection in high-risk populations, particular in people with chronic kidney disease, heart failure, and diabetes, has been a tremendous challenge. The hope is that, with the approval of aliskiren/valsartan, physicians can target two key points of the RAAS and ultimately help patients reach a healthier BP range while also obtaining cardiovascular protection to prevent future events.