Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: The HOPE randomized trial

Background: The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. Objective: To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Design: Post hoc analysis. Setting: The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. Patients: 980 patients with mild renal insufficiency (serum creatinine concentration greater than or equal to 124 mu mol/L [greater than or equal to 1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 mu mol/L [<1.4 mg/dl]) Patients with a baseline serum creatinine concentration greater than 200 mu mol/L (2.3 mg/dL) were excluded. Measurements: The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke. Results: Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% Cl, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference). Conclusions: In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.