Aliskiren/valsartan combination for the treatment of cardiovascular and renal diseases

Chronic activation of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the development of hypertension, and cardiac and renal diseases. RAAS inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), improve cardiovascular and renal outcomes. However, studies have shown that residual morbidity and mortality remains high, despite current optimal treatment. More comprehensive control of the RAAS might provide additional reductions in morbidity and mortality. Direct renin inhibitors offer the potential for enhanced RAAS control as they target the system at the point of activation, thereby reducing plasma renin activity (PRA); by contrast, ARBs and ACE inhibitors increase PRA. Elevated PRA is independently associated with cardiovascular morbidity and mortality. A single-pill combination of the direct renin inhibitor, aliskiren, and the ARB, valsartan, at once-daily doses of 150/160 mg and 300/320 mg, has recently been approved by the US FDA for the treatment of hypertension in patients not adequately controlled on aliskiren or ARB monotherapy, and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. This article examines the efficacy, safety and tolerability of aliskiren/valsartan combination therapy, and considers the evidence for the potential organ-protection benefits of this treatment.