Dual Blockade of the Renin-Angiotensin System for Cardiorenal Protection: An Update

The renin-angiotensin system (RAS) has an important role in hypertension and the continuum of cardiovascular and kidney disease. The inhibition of this system, either with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), has been shown to be beneficial for cardiorenal protection. Dual blockade with an ACE inhibitor and ARB may have additional benefits due to the more complete inhibition of the system. Most published trials, including recent large studies and meta-analyses, have reported either limited or no additional benefit. Dual-blockade therapy seems to have some benefit on proteinuria and blood pressure reduction, and on morbidity and mortality in patients with heart failure, compared with monotherapy. The major issue arising from these published trials and meta-analyses is the increased frequency of dual therapy discontinuation and adverse effects on kidney function. There is a lack of hard end-point data for renal outcomes and long-term safety data in most published trials. Until the results of ongoing trials become available and as further safety data emerge, a wise approach would be to withhold use of ACE inhibitor and ARB combination therapy in general practice. When used in selected conditions, patients need to be closely monitored.

Index Words: Renin-angiotensin system, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dual blockade, hypertension, cardiovascular disease, chronic kidney disease, proteinuria, clinical trials