Direct inhibition of renin: a physiological approach to treat hypertension and cardiovascular disease.Future Cardiol. 2009 Sep; 5(5):453-65.FC
Despite the last three decades of progress in improving cardiovascular outcomes via renin-angiotensin-aldosterone system (RAAS) blockade in hypertensive patients, substantial residual morbidity/mortality remains. Attempts to improve clinical outcomes by combining angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have yielded mixed results. Adverse effects of RAAS blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may relate to compensatory increases in plasma renin activity (PRA). The first-in-class direct renin inhibitor, aliskiren, blocks the RAAS at its point-of-activation, suppressing PRA and attenuating increases associated with other antihypertensives. Aliskiren (with or without other agents) provides significant and prolonged blood pressure reductions in a broad range of hypertensive patients and is well tolerated. Initial results from organ-protection studies are promising. Long-term outcomes studies should yield valuable information regarding the significance of direct renin inhibition in clinical practice.