However, we feel that some patients would put a large value on the CV protection from RASi and would be willing to tolerate the potential harms, particularly patients with higher GFR and a relatively low risk of harm. www.kidney-international.org chapter 3 The HOPE study, one of the largest RASi studies, reported CV bene ts with an ACEi versus placebo in people at high CV risk with or without high BP.163 In a prespeci ed CKD sub- group (CrCl <65 ml/min by the Cockcroft-Gault formula) of 3394 patients with no or mildly increased albuminuria (approximately one-third of whom had diabetes), ACEi reduced the risk for all-cause mortality by 20% (HR: 0.80; during a mean follow-up of 4.5 years.167 In the overall HOPE study, 3577 patients had diabetes, and 2437 of them (roughly two-thirds) did not have albuminuria.163 The PEACE sub- study in those with CKD con rmed this notion.165 Practice Point 3.2.2: RASi (ACEi or ARB) should be administered using the highest approved dose that is tolerated to achieve the bene ts described because the proven bene ts were achieved in trials using these doses. The Work Group judged that a large majority of physicians would be comfortable initiating RAS blockade treatment and titrating it to the maximum dose approved by regulatory agencies and tolerated by the patient because of its bene ts in kidney protection, their familiarity with this drug, and its good safety pro le. The bene ts from RASi administered in less than maximally recommended doses are less certain. However, if for whatever reason (e.g., hyperkalemia) the patient cannot tolerate the maximum dose, a smaller dose may still be reasonable. 