Cardiovascular Outcomes in the Irbesartan Diabetic Nephropathy Trial of Patients with Type 2 Diabetes and Overt Nephropathy

Tomas Berl, Lawrence G. Hunsicker, Julia B. Lewis, Marc A. Pfeffer, Jerome G. Porush, Jean Lucien Rouleau, Paul L. Drury, Enric Esmatjes, Donald Hricik, Chirag R. Parikh, Itamar Raz, Philippe Vanhille, Thomas B. Wiegmann, Bernard M. Wolfe, Francesco Locatelli, Samuel Z. Goldhaber, Edmund J. Lewis

Research output: Contribution to journalArticlepeer-review

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. 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 μmol/L (1.0 mg/dL) to 266 μmol/L (3.0 mg/dL) in women and 106 μmol/L (1.2 mg/dL) to 266 μmol/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.

Original languageEnglish (US)
Pages (from-to)542-549+I43
JournalAnnals of internal medicine
Volume138
Issue number7
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine

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