Dual blockade of the renin–angiotensin–aldosterone system in cardiac and renal disease

PURPOSE OF REVIEW: Renin-angiotensin-aldosterone system (RAAS) blockade improves outcome in cardiovascular disease (CVD) and chronic kidney disease (CKD), but the residual risk during monotherapy RAAS blockade remains very high. This review discusses the place of dual RAAS blockade in improving these outcomes. RECENT FINDINGS: The combination of angiotensin-converting enzyme inhibitor (ACEI) with angiotensin II type 1 receptor blocker (ARB) generally had a better antihypertensive and antiproteinuric effect than monotherapy in many studies, but is also associated with more adverse effects. Unfortunately, the effect on hard renal and cardiovascular endpoints is not unequivocal. The combination of ACEI (or ARB) with aldosterone blockade has long-term benefits in heart failure, and an added effect on proteinuria in CKD, but data on hard renal endpoints are lacking. Dual blockade including renin inhibition has added antiproteinuric effects, but studies to gather long-term data are still under way. Available strategies to optimize the effect of monotherapy RAAS blockade include dose titration and correction of volume excess. Whether dual blockade has better efficacy and/or fewer adverse effects than optimized monotherapy has not been investigated. SUMMARY: Several options are available to increase the effect of monotherapy RAAS blockade. For proteinuric CKD, these can be combined in a stepwise approach aimed at maximal proteinuria reduction; this includes dual blockade for patients with persistent proteinuria during optimized monotherapy RAAS blockade. Long-term randomized studies, however, are needed to support the benefits of dual blockade for long-term renal and cardiovascular outcome in CKD.