Dual RAS therapy not on target, but fully alive

Inhibitors of the renin-angiotensin system (RAS) form a cornerstone in the treatment of kidney disease. These drugs lower blood pressure and albuminuria, and afford renal protection. Dual therapy with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker have been shown to be more effective in reducing blood pressure and albuminuria than the single use of these agents. It was therefore expected that the combination of these drugs could delay the progression of renal disease. However, the ONTARGET renal analysis suggests that the use dual-agent RAS leads to increased renal risk. This led to vivacious discussions about the benefits and risks of dual-agent RAS in patients with nephropathy. We will review the ONTARGET trial design and interpretation, and offer implications for novel trials.