Cardiorenal end points in a trial of aliskiren for type 2 diabetes

Background: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. Methods: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren ( 300 mg daily ) or placebo as an adjunct to an angiotensin-converting–enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. Results: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients ( 18.3% ) assigned to aliskiren as compared with 732 ( 17.1% ) assigned to placebo ( hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12 ). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren ( between-group differences, 1.3 and 0.6 mm Hg, respectively ) and the mean reduction in the urinary albumin-to-creatinine ratio was greater ( between-group difference, 14 percentage points; 95% CI, 11 to 17 ). The proportion of patients with hyperkalemia ( serum potassium level, ≥6 mmol per liter ) was significantly higher in the aliskiren group than in the placebo group ( 11.2% vs. 7.2% ), as was the proportion with reported hypotension ( 12.1% vs. 8.3% ) ( P < 0.001 for both comparisons ). Conclusions: The addition of aliskiren to standard therapy with renin–angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. ( Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757. )