Dual renin-angiotensin system blockade in the ONTARGET study: clinically relevant risk for the kidney?

Inhibition of the renin-angiotensin system contributes to reductions in proteinuria and in progression of chronic kidney disease. Indeed, monotherapy with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) has been shown to decrease proteinuria and slow the decline of chronic kidney disease, but incompletely. Therefore, there is increasing interest in whether combination strategies will provide more complete blockade of the renin-angiotensin system, which may translate into superior renoprotective and cardioprotective effects compared with either agent alone. There have been several reports on combination strategies. However, the recent report of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) has received much of the attention. The renal outcomes in ONTARGET suggest that combined ACE inhibitor and ARB therapy contributes to a higher rate of adverse renal outcomes than monotherapy. Therefore, this review explores data from ONTARGET in relation to other available evidence on the use of combination therapies.