Author + information
- Received May 27, 2004
- Revision received September 20, 2004
- Accepted October 26, 2004
- Published online March 1, 2005.
- Kristian Wachtell, MD, PhD*,†,* (, )
- Mika Lehto, MD‡,
- Eva Gerdts, MD, PhD§,
- Michael H. Olsen, MD, PhD*,
- Björn Hornestam, MD∥,
- Björn Dahlöf, MD, PhD, FACC∥,
- Hans Ibsen, MD*,
- Stevo Julius, MD, FACC¶,
- Sverre E. Kjeldsen, MD, PhD, FACC¶,#,
- Lars H. Lindholm, MD, FACC**,
- Markku S. Nieminen, MD, FACC‡ and
- Richard B. Devereux, MD, FACC†
- ↵*Reprint requests and correspondence:
Dr. Kristian Wachtell, Rigshospitalet, Department of Medicine B2142, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark
Objectives This study was designed to evaluate whether different antihypertensive treatment regimens with similar blood pressure reduction have different effects on new-onset atrial fibrillation (AF).
Background It is unknown whether angiotensin II receptor blockade is better than beta-blockade in preventing new-onset AF.
Methods In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study 9,193 hypertensive patients and patients with electrocardiogram-documented left ventricular hypertrophy were randomized to once-daily losartan- or atenolol-based antihypertensive therapy. Electrocardiograms were Minnesota coded centrally, and 8,851 patients without AF by electrocardiogram or history, who were thus at risk of developing AF, were followed for 4.8 ± 1.0 years.
Results New-onset AF occurred in 150 patients randomized to losartan versus 221 to atenolol (6.8 vs. 10.1 per 1,000 person-years; relative risk 0.67, 95% confidence interval [CI] 0.55 to 0.83, p < 0.001) despite similar blood pressure reduction. Patients receiving losartan tended to stay in sinus rhythm longer (1,809 ± 225 vs. 1,709 ± 254 days from baseline, p = 0.057) than those receiving atenolol. Moreover, patients with new-onset AF had two-, three- and fivefold increased rates, respectively, of cardiovascular events, stroke, and hospitalization for heart failure. There were fewer composite end points (n = 31 vs. 51, hazard ratio = 0.60, 95% CI 0.38 to 0.94, p = 0.03) and strokes (n = 19 vs. 38, hazard ratio = 0.49, 95% CI 0.29 to 0.86, p = 0.01) in patients who developed new-onset AF in the losartan compared to the atenolol treatment arm of the study. Furthermore, Cox regression analysis showed that losartan (21% risk reduction) and new-onset AF both independently predicted stroke even when adjusting for traditional risk factors.
Conclusions Our novel finding is that new-onset AF and associated stroke were significantly reduced by losartan- compared to atenolol-based antihypertensive treatment with similar blood pressure reduction.
Drs. Wachtell, Olsen, Dahlöf, Ibsen, Julius, Kjeldsen, Lindholm, Nieminen and Devereux have received grant support from Merck and Co., Inc. The trial was supported by an unrestricted grant from Merck and Co. The presentation of data is the intellectual property of the LIFE Steering Committee, and Merck has reviewed the manuscript.
- Received May 27, 2004.
- Revision received September 20, 2004.
- Accepted October 26, 2004.
- American College of Cardiology Foundation