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.
OBJECTIVE
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.
Wachtell
Kristian
K
Department of Medicine, Glostrup University Hospital, Glostrup, Denmark. kristian@wachtell.net
Lehto
Mika
M
Gerdts
Eva
E
Olsen
Michael H
MH
Hornestam
Björn
B
Dahlöf
Björn
B
Ibsen
Hans
H
Julius
Stevo
S
Kjeldsen
Sverre E
SE
Lindholm
Lars H
LH
Nieminen
Markku S
MS
Devereux
Richard B
RB
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000401:mortality; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001262:Atenolol; D019808:Losartan