title: Cardiorenal end points in a trial of aliskiren for type 2 diabetes.
abstract: 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.).
authors.affiliation: Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. hhparving@dadlnet.dk
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Barry M
authors.initials: BM
authors.lastname: Brenner
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Nish
authors.initials: N
authors.lastname: Chaturvedi
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Desai
authors.forename: Maria
authors.initials: M
authors.lastname: Nicolaides
authors.forename: Alexia
authors.initials: A
authors.lastname: Richard
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Xiang
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunel
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
mesh_terms: D000368:Aged; D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D007008:Hypokalemia; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D017211:Treatment Failure; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren