Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy

Ann Intern Med. 2003 Apr 1;138(7):542-9. doi: 10.7326/0003-4819-138-7-200304010-00010.


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.

Design: Randomized double-blind, placebo-controlled trial with a median follow-up of 2.6 years. A time event analysis was used.

Setting: 209 centers in the Americas, Europe, Israel, and Australasia.

Participants: 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.

Intervention: Treatment with irbesartan, amlodipine, or placebo.

Measurements: 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).

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amlodipine / therapeutic use
  • Angiotensin II
  • Angiotensin Receptor Antagonists*
  • Antihypertensive Agents / therapeutic use*
  • Biphenyl Compounds / therapeutic use*
  • Calcium Channel Blockers / therapeutic use
  • Cardiovascular Diseases / prevention & control*
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Angiopathies / drug therapy
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / drug therapy*
  • Irbesartan
  • Kidney Failure, Chronic / etiology
  • Male
  • Middle Aged
  • Placebos
  • Risk Factors
  • Tetrazoles / therapeutic use*
  • Treatment Outcome


  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Calcium Channel Blockers
  • Placebos
  • Tetrazoles
  • Angiotensin II
  • Amlodipine
  • Creatinine
  • Irbesartan