title: Renal function and effectiveness of angiotensin-converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the Prevention of Events with ACE inhibition (PEACE) trial.
abstract: BACKGROUND
  Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes. In the post-myocardial infarction setting, angiotensin-converting enzyme (ACE) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function.
  
  
  RESULTS
  We assessed the relation between renal function and outcomes, the influence of ACE inhibition on this relation, and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial (PEACE). Patients (n=8290) were randomly assigned to receive trandolapril (target, 4 mg/d) or placebo. Clinical creatinine measures were available for 8280 patients before randomization. The estimated glomerular filtration rate (eGFR) was calculated with the 4-point Modification of Diet in Renal Disease equation. Renal function was related to outcomes, and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling. The mean eGFR in PEACE was 77.6+/-19.4, and 1355 (16.3%) patients had reduced renal function (eGFR <60 mg.mL(-1).1.73 m(-2)). We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality (P=0.02). Trandolapril was associated with a reduction in total mortality in patients with reduced renal function (adjusted HR, 0.73; 95% CI, 0.54 to 1.00) but not in patients with preserved renal function (adjusted HR, 0.94; 95% CI, 0.78 to 1.13).
  
  
  CONCLUSIONS
  Although trandolapril did not improve survival in the overall PEACE cohort, in which mean eGFR was relatively high, trandolapril reduced mortality in patients with reduced eGFR. These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, Massachusetts 02115, USA. ssolomon@rics.bwh.harvard.edu
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Madeline M
authors.initials: MM
authors.lastname: Rice
authors.forename: Kathleen
authors.initials: K
authors.lastname: A Jablonski
authors.forename: Powell
authors.initials: P
authors.lastname: Jose
authors.forename: Michael
authors.initials: M
authors.lastname: Domanski
authors.forename: Marc
authors.initials: M
authors.lastname: Sabatine
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Jean
authors.initials: J
authors.lastname: Rouleau
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril