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Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy

Ibsen, Hansa; Wachtell, Kristiana,b; Olsen, Michael Ha; Borch-Johnsen, Knutc; Lindholm, Lars Hd; Mogensen, Carl Erike; Dahlöf, Björnf; Devereux, Richard Bb; de Faire, Ulfg; Fyhrquist, Frejh; Julius, Stevoi; Kjeldsen, Sverre Ej; Lederballe-Pedersen, Olek; Nieminen, Markku Sh; Omvik, Perl; Oparil, Suzannem; Wan, Yingn

Original papers: Kidney

Objectives To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria.

Design Double-blind, randomized, controlled trial of 4.8 years.

Setting Out-patient setting.

Patients A total of 8206 with hypertension and left ventricular hypertrophy.

Interventions Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg

Main outcome measures The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke.

Results The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan.

Conclusions Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.

aGlostrup University Hospital, Denmark, bWeill Medical College of Cornell University, New York, USA, cSteno Diabetes Centre, Gentofte, Denmark, dUmeå University Hospital, Sweden, eÅrhus Univeristy Hospital, Denmark, fSahlgrenska University Hospital/Östra, Göteborg, gKarolinska University Hospital, Stockholm, Sweden, hHelsinki University Central Hospital, Finland, iUniversity of Michigan, Ann Arbor, Michigan, USA, jUllevaal University Hospital, Oslo, Norway, kViborg Hospital, Denmark, lHaukeland University Hospital, Bergen, Norway, mUniversity of Alabama, Birmingham, Alabama and nMerck Research Laboratories, West Point, Pennsylvania, USA.

Sponsorship: The LIFE study was sponsored by Merck & Co., Inc. The authors have received grant support from Merck. Y.W. is an employee of Merck.

Correspondence and requests for reprints to Hans Ibsen, Chief Physician, Medical Department M, Glostrup Hospital, DK-2600 Glostrup, Denmark. Tel: +45 43 23 32 16; fax: +45 43 23 39 12; e-mail:

Received 23 March 2004 Revised 17 May 2004 Accepted 18 May 2004

See editorial commentary on page 1679

Previous presentation: These data were presented at the European Society of Hypertension meeting, Milan, Italy, June 2003.

© 2004 Lippincott Williams & Wilkins, Inc.