Direct renin inhibitors like aliskiren have shown renoprotective and cardioprotective benefits on surrogate endpoints in diabetes, with ongoing trials assessing clinical morbidity and mortality.
Do direct renin inhibitors provide additional cardioprotective and renoprotective benefits in patients with diabetes?
Direct renin inhibitors represent a potential therapeutic option for target organ protection in diabetes, pending results from hard outcome trials like ALTITUDE.
Cardiovascular (CV) and renal complications associated with diabetes can be attenuated with antihypertensives that work on the renin-angiotensin-aldosterone system (RAAS),particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and possibly direct renin inhibitors (DRIs). Cardioprotective and renoprotective benefits are independent of the blood pressure-lowering effect of the RAAS inhibitor. Given more complete RAAS blockade, evidence has suggested that the use of ACE inhibitor/ARB combination therapy may provide greater target organ protection. However, recent data have challenged this assumption. Although advances have been made in reducing diabetic nephropathy progression through use of ACE inhibitors and ARBs, improvement in organ protection is needed because diabetes remains the leading cause of end-stage renal disease. Despite the use of these agents in patients with CV disease and diabetes, CV adverse events remain high, suggesting the need for improved outcomes. Newer agents such as DRIs may have the potential to offer similar target organ protection. The first DRI, aliskiren, administered alone or in combination with other RAAS inhibitors, has been shown to confer renoprotective and cardioprotective benefits in human and animal studies that have measured surrogate endpoints. An ongoing outcomes study (Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints ALTITUDE), which is assessing renal and CV morbidity and mortality, will further define whether aliskiren provides additional benefits beyond RAAS inhibition and lowering of blood pressure.
Raymond O. Estacio (Fri,) conducted a review in Diabetes with cardiovascular and renal complications. Direct renin inhibitors (aliskiren) vs. ACE inhibitors, ARBs was evaluated. Direct renin inhibitors like aliskiren have shown renoprotective and cardioprotective benefits on surrogate endpoints in diabetes, with ongoing trials assessing clinical morbidity and mortality.