Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy.
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.
Berl
Tomas
T
University of Colorado Medical School, Denver, Colorado, USA.
Hunsicker
Lawrence G
LG
Lewis
Julia B
JB
Pfeffer
Marc A
MA
Porush
Jerome G
JG
Rouleau
Jean-Lucien
JL
Drury
Paul L
PL
Esmatjes
Enric
E
Hricik
Donald
D
Parikh
Chirag R
CR
Raz
Itamar
I
Vanhille
Philippe
P
Wiegmann
Thomas B
TB
Wolfe
Bernard M
BM
Locatelli
Francesco
F
Goldhaber
Samuel Z
SZ
Lewis
Edmund J
EJ
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
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