Unmet Needs in Managing Hypertension: Potential Role of Direct Renin Inhibition

Hypertension is the most prevalent and important risk factor for cardiovascular and renal disease worldwide. Despite the large armamentarium of available blood pressure-lowering agents, the need remains for safer and more effective antihypertensive treatment. Based on current target levels of < 140/90 mm Hg, only one-third of hypertensive Americans have achieved goal blood pressure. Several strategies can help address these challenges, including increasing public awareness, and improving physician awareness of evidence-based therapeutic guidelines. There also remains a need for new therapeutic options. This review examines new developments among those agents having inhibitory activity on the renin-angiotensin-aldosterone system (RAAS). All currently available RAAS blockers cause a reactive increase in plasma renin concentration. However, the direct renin inhibitors are the only class that diminishes plasma renin activity, an effect that may provide additional cardiovascular and/or renoprotective benefit. Aliskiren is the first clinically available direct renin inhibitor that has been shown to be effective and well tolerated both as monotherapy and in combination with other established agents in hypertensive patients. Randomized clinical trials are underway to explore the extent to which direct renin inhibition provides additive protection against cardiovascular and renal disease events.