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(Circulation. 2002;105:e9100.)
© 2002 American Heart Association, Inc.

Cardiovascular News

JoAnn Lindenfeld, MD; Jeffrey Borer, MD; Paul W. Armstrong, MD

Losartan potassium (Cozaar), manufactured by Merck and Company, Inc, was proposed for the prevention of progression of nephropathy in patients with type II diabetes. Losartan is an angiotensin II receptor blocker (ARB) previously approved for the treatment of hypertension. It was examined in the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) study of 1513 normotensive/hypertensive patients with type II diabetes and nephropathy. At baseline, these patients had mean systolic and diastolic blood pressures of 152 mm Hg and 82 mm Hg, respectively, a mean creatinine of 1.9 mg/dL, and a mean proteinuria (UA/Cr) of 1808 mg/g Cr. Although patients could have received an ACE inhibitor or ARB in the past, no such treatment was allowed for the enrolled patients during the course of the trial.

The primary hypothesis was that long-term treatment with losartan, beginning with a daily dose of 50 mg and increasing to 100 mg, would reduce the primary composite triple end point of a doubling of serum creatinine. It would also reduce the development of end-stage renal disease (ESRD, defined as the need for chronic dialysis or renal transplantation) and all-cause mortality. Because proteinuria has been demonstrated to be an independent risk factor for the progression of renal disease in diabetic and nondiabetic patients, subjects were stratified by baseline proteinuria according to UA/Cr <2000 mg/Cr or 2000 mg/Cr.

Although the original study was to conclude after 3.5 years of follow-up, the Steering Committee recommended early termination of the trial because of increasing evidence . . . [Full Text of this Article]