The role of direct renin inhibition in clinical practice: focus on combination therapy

Monotherapy with most antihypertensive agents reduces systolic BP by about 10 mmHg ('Rule of 10'). Thus, the majority of hypertensive patients require combination therapy to achieve BP goals. In this review, we provide a brief overview of the renin-angiotensin-aldosterone system (RAAS) and discuss the rationale, clinical evidence, and shortcomings related to the use of angiotensin-converting enzyme (ACE) inhibitors in combination with angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We summarize the rationale and clinical evidence supporting the use of the direct renin inhibitor (DRI) aliskiren, particularly in combination with other antihypertensive classes, including in high-risk patients with diabetes mellitus and with or without diabetic nephropathy. DRIs may be useful in combination with ACE inhibitors or ARBs as they provide a more complete blockade of the RAAS, effectively suppressing residual angiotensin II production and the counter-regulatory increase in plasma renin activity observed in patients receiving monotherapy with ACE inhibitors or ARBs.