In the main study of the PEACE trial, the overall treatment effect of trandolapril was neutral (10). The investigators performed subgroup analyses for possible explanations for this neutral finding. They stated that their study consisted of relatively few patients with poor renal function (16.3% eGFR <60). Trandolapril reduced the incidence of total mortality only in patients with poor renal function. Because of this low prevalence in the PEACE trial, the investigators stated that this could potentially explain the overall neutral results. However, the distribution of eGFR in the EUROPA trial was similar (15.9% eGFR <60). Still, the overall effect of the main EUROPA study was in favor of ACE inhibition therapy (2). The different result in the PEACE trial may be explained by the fact that the PEACE study potentially had the lowest-risk population. Renal insufficiency could identify a higher risk subgroup and hence explain why the PEACE trial shows a benefit only in this subgroup in an otherwise low-risk population. However, subgroup analyses of the HOPE and EUROPA studies in low-risk groups showed similar event rates compared with those of the PEACE study, and in low-risk groups of the EUROPA study, perindopril reduced the risk of cardiovascular mortality and nonfatal MI by 17%, contrasting with 3% in the PEACE trial. These analyses indicate that the apparent neutral results of the PEACE trial may not be attributable to the lower risk of these patients nor to the background therapies used, but rather are related to the reduced power of the PEACE trial caused by greater crossover and shorter follow-up than in the other studies (1- 2,4,10,19). In addition, the different results may be related to substance-specific or (target) dose-dependent differences between ACE inhibitors potentially in relation to the level of renal function, which may have resulted in suboptimal dosages (22). In the EUROPA trial, patients were assigned to receive a relatively high dose of perindopril (8 mg), which was achieved rapidly and in a high proportion of patients, whereas in the PEACE trial, trandolapril was up-titrated to the target dose (4 mg) only 6 months after randomization. At 3 years, target dose was achieved in 57.8% of patients in the PEACE trial and 93.0% of patients in the EUROPA trial. Both agents are in a broadly similar ACE inhibitor subgroup, share chemical moieties, are lipophilic, and are mainly excreted from the kidney and were used in doses that showed important pharmacologic effects. Still, without head-to-head trials it cannot be excluded that there are pharmacologic differences between the agents, possibly in relation to renal insufficiency, that are important to their clinical efficacy to reduce cardiovascular end points (22).