CLINICAL RESEARCH: LVH AND ARRHYTHMIAS
Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol
The Losartan Intervention For End point reduction in hypertension (LIFE) study
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
* Department of Medicine, Glostrup University Hospital, Glostrup, Denmark
Division of Cardiology, Weill Medical College of Cornell University, New York, New York
Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
Department of Cardiology, Haukeland University Hospital, Bergen, Norway
|| Department of Medicine, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
¶ Department of Medicine, University of Michigan, Ann Arbor, Michigan
# Department of Medicine, Ullevål University Hospital, Oslo, Norway
** Department of Preventive Medicine, Umeå University Hospital, Umeå, Sweden
Manuscript received May 27, 2004;
revised manuscript received September 20, 2004,
accepted October 26, 2004.
* Reprint requests and correspondence: Dr. Kristian Wachtell, Rigshospitalet, Department of Medicine B2142, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark (Email: kristian{at}wachtell.net).
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.
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Abbreviations and Acronyms
| | AF = atrial fibrillation | | CI = confidence interval | | ECG = electrocardiographic | | HF = heart failure | | HR = hazard ratio | | LV = left ventricular/ventricle | | LIFE = Losartan Intervention For Endpoint reduction in hypertension study |
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