The composite of doubling of serum creatinine or ESKD was reached in 18 versus 40 partici- pants (ramipril vs. placebo, P 0.02).176 In the REIN Stratum-1 of 186 patients with proteinuria of >1 to <3 g/d, the decline in GFR was not different, but ESKD events were less with ramipril chapter 3 www.kidney-international.org The Angiotensin-Converting Enzyme Inhibitors and Kidney Protection (AIPRI) trial compared benazepril to placebo in pa- tients with CKD mostly without diabetes to assess its effect on CKD progression (doubling of serum creatinine or ESKD as the primary outcome). Benazepril also caused a 53% reduction of the A meta-analysis of these 2 trials found a 49% decrease (RR: 0.51; 95% CI: 0.38 0.69) in the composite outcome, ESKD and a doubling of serum creati- nine with 769 participants (Supplementary Table S15).177,178 CV bene t from ACEi in these 3 aforementioned studies was assessed by meta-analysis, with the addition of the study by Hou et al.179 A reduction of CV events of 42% was found ). There are several meta-analyses reporting greater bene ts of ACEi or ARBs on kidney outcomes with increasing albuminuria, as for example, from Jafar et al.166,180 The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study directly compared benazepril (ACEi) to los- artan (ARB) in 360 patients with CKD without diabetes and mean proteinuria of 1.4 2.0 g/d.181 No differences were found in kidney outcomes (primary outcome) or CV events between the 2 classes of RASi. Many of the above trials examined RASi versus placebo in people on background antihypertensive therapy. Few trials also tested active comparators to RASi (e.g., AASK, IDNT). 