Blocking the renin-angiotensin-aldosterone system in two ways improves blood pressure control, but other approaches may be safer and more effective.
The oral renin inhibitor aliskiren was recently approved by the FDA for treatment of hypertension, as monotherapy or in combination with other drugs. Aliskiren blocks the renin-angiotensin-aldosterone (RAA) system at an earlier step than angiotensin-converting–enzyme inhibitors or angiotensin-receptor blockers (ARBs). Combinations of ACE inhibitors and ARBs have not been consistently more effective than either drug alone. Might a combination of aliskiren and an ARB lower blood pressure more effectively than either agent alone?
Researchers randomized 1797 hypertensive patients (mean diastolic pressure, 95–110 mm Hg) to receive half-maximal doses of aliskiren, valsartan, both, or placebo for 8 weeks, with titration to maximal doses. The study was supported by the manufacturer of both drugs.
After 8 weeks, mean reductions in diastolic pressure were significantly greater in the combination group (12.2 mm Hg) than in either monotherapy group (9.0 mm Hg for aliskiren, 9.7 mm Hg for valsartan) or in the placebo group (4.1 mm Hg). Similar results were seen for mean systolic pressure and other measures of blood pressure control. Patients who received combination therapy had a higher incidence of transient hyperkalemia (>5.5 mmol/L) than those who received monotherapy or placebo.
Comment: All agents that block the RAA system increase renin secretion by decreasing negative feedback exerted on the kidney by angiotensin II. Aliskiren’s added antihypertensive effect may derive from blockade of some secondary effects of this increased renin secretion. But editorialists suggest that adding a renin inhibitor to a drug acting outside the RAA system is likely to be safer and more effective than combining aliskiren with an ARB. Data on prevention of cardiovascular morbidity and mortality are not yet available.
Published in Journal Watch General Medicine August 2, 2007
Oparil S et al. Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: A randomised, double-blind trial. Lancet 2007 Jul 21; 370:221-9.