Agents that block the renin-angiotensin-aldosterone system (RAAS) are the cornerstones of antihypertensive therapy in patients at high risk for cardiovascular or renal disease. Recently, it was shown that activation of RAAS may occur through alternate pathways not inhibited by angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs), and that ACEIs, ARBs, or MRAs may actually cause a reactive increase in plasma renin concentration and activity. While these agents, alone or in combination, decrease blood pressure and cardiovascular events to varying degrees, the direct renin inhibitor is a new class of RAAS blocking agent. Aliskiren is the first US Food and Drug Administration-approved direct renin inhibitor with good oral bioavailability. ASPIRE HIGHER is an ongoing series of clinical trials designed to investigate the effect of aliskiren on cardiovascular/renal surrogate endpoints and morbidity/mortality in patients with hypertension and high risk for cardiovascular or renal disease.
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