title: Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy.
abstract: BACKGROUND
  Patients with diabetes have increased risk for adverse cardiovascular events. Angiotensin-converting enzyme inhibitors are protective in type 1 diabetes. However, no definitive studies have examined the use of angiotensin-receptor blockers in patients with type 2 diabetes and overt nephropathy. The primary outcomes of the Irbesartan Diabetic Nephropathy Trial were doubling of serum creatinine levels, end-stage renal disease, and death from any cause.
  
  
  OBJECTIVE
  To compare rates of cardiovascular events among patients with type 2 diabetic nephropathy who received conventional antihypertensive therapy with an angiotensin-receptor blocker (irbesartan) or a calcium-channel blocker (amlodipine), or placebo.
  
  
  METHODS
  Randomized double-blind, placebo-controlled trial with a median follow-up of 2.6 years. A time event analysis was used.
  
  
  METHODS
  209 centers in the Americas, Europe, Israel, and Australasia.
  
  
  METHODS
  1715 adults with type 2 diabetic nephropathy and hypertension; serum creatinine levels of 89 micromol/L (1.0 mg/dL) to 266 micromol/L (3.0 mg/dL) in women and 106 micromol/L (1.2 mg/dL) to 266 micromol/L (3.0 mg/dL) in men; and urinary protein excretion rates of at least 900 mg/d.
  
  
  METHODS
  Treatment with irbesartan, amlodipine, or placebo.
  
  
  METHODS
  Time to cardiovascular death, myocardial infarction, congestive heart failure, strokes, and coronary revascularization.
  
  
  RESULTS
  The three groups were not statistically different in the composite of cardiovascular events. Among the components of the composite, there was a trend toward a decrease in strokes in patients receiving amlodipine versus those receiving placebo (hazard ratio, 0.65 [95% CI, 0.35 to 1.22]; P = 0.18). Likewise, patients receiving amlodipine had a significantly lower rate of myocardial infarction when compared with placebo recipients (hazard ratio, 0.58 [CI, 0.37 to 0.92]; P = 0.02). In contrast, patients receiving irbesartan had a significantly lower incidence of congestive heart failure when compared with placebo recipients (hazard ratio, 0.72 [CI, 0.52 to 1.00]; P = 0.048) or amlodipine recipients (hazard ratio, 0.65 [CI, 0.48 to 0.87]; P = 0.004).
  
  
  CONCLUSIONS
  The composite cardiovascular event rate did not differ in patients with type 2 diabetes and overt nephropathy treated with irbesartan, amlodipine, or placebo in addition to conventional antihypertensive therapy.
authors.affiliation: University of Colorado Medical School, Denver, Colorado, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Berl
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunsicker
authors.forename: Julia B
authors.initials: JB
authors.lastname: Lewis
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Jerome G
authors.initials: JG
authors.lastname: Porush
authors.forename: Jean-Lucien
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Paul L
authors.initials: PL
authors.lastname: Drury
authors.forename: Enric
authors.initials: E
authors.lastname: Esmatjes
authors.forename: Donald
authors.initials: D
authors.lastname: Hricik
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Philippe
authors.initials: P
authors.lastname: Vanhille
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Wiegmann
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Wolfe
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lewis
mesh_terms: D017311:Amlodipine / Q000627:therapeutic use; D000804:Angiotensin II; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000077405:Irbesartan; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D010919:Placebos; D013777:Tetrazoles; D000804:Angiotensin II; D017311:Amlodipine; D003404:Creatinine; D000077405:Irbesartan