1. Atrial Fibrillation Findings in the LIFE Trial
Slide 1

2. Outline Background — Atrial Fibrillation (AF) and Cardiovascular Risk
New-Onset AF in the LIFE Trial
Reduced Cardiovascular Risk in Patients with AF at Baseline
Overall Conclusions
Slide 2
Background — Atrial Fibrillation (AF) and Cardiovascular Risk
New-Onset AF in the LIFE Trial
Reduced Cardiovascular Risk in Patients with AF at Baseline
Overall Conclusions

3. Background AF increases cardiovascular morbidity and mortality
AF increases risk of stroke
Patients with hypertension have an increased risk of developing AF
The combination of hypertension and AF further increases cardiovascular risk
Slide 3
AF increases cardiovascular morbidity and mortality
AF increases risk of stroke
Patients with hypertension have an increased risk of developing AF
The combination of hypertension and AF further increases cardiovascular risk
Benjamin EJ et al Circulation 1998;98:946–952; Krahn AD et al Am J Med 1995;98:476–484; Hart RG et al Ann Intern Med 2003;138:831–838; Straus SE et al JAMA 2002;288:1388–1395.

4. Recently published in the Journal of the American College of Cardiology
Kristian Wachtell, Mika Lehto, Eva Gerdts, Michael H. Olsen, Björn Hornestam, Björn Dahlöf, Hans Ibsen, Stevo Julius, Sverre E. Kjeldsen, Lars H. Lindholm, Markku S. Nieminen, Richard B. Devereux
Angiotensin II Receptor Blockade Reduces New-Onset Atrial Fibrillation and Subsequent Stroke Compared to Atenolol: The LIFE Study
Slide 4
J Am Coll Cardiol 2005;45:712–719.

5. LIFE AF Substudy Design
8851 hypertensive patients with left ventricular hypertrophy (LVH) but without AF
Random assignment to once-daily losartan or once-daily atenolol for a mean of 4.8 years
ECGs at baseline and at yearly follow-up
Slide 5
In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, 9193 hypertensive patients and patients with electrocardiographic evidence of left ventricular hypertrophy (LVH) were randomized to once-daily losartan- or atenolol-based antihypertensive therapy.6
Electrocardiograms (ECGs) were Minnesota coded centrally at a single core laboratory, and 8851 patients without electrocardiographic evidence or a history of AF, but who were thus at risk of developing AF, were followed for 4.8 ± 1.0 years. ECGs were obtained at baseline and at the yearly follow-up visits.5
ECG=electrocardiograms
Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

6. Design/Dosing Titration
Titration to target blood pressure: <140/90 mmHg*
Losartan 100 mg + HCTZ mg + others**
Losartan 100 mg + HCTZ 12.5 mg*
Losartan 50 mg + HCTZ 12.5 mg*
Losartan 50 mg
Placebo
Atenolol 50 mg
Atenolol 50 mg + HCTZ 12.5 mg*
Atenolol 100 mg + HCTZ 12.5 mg*
Slide 6
Atenolol 100 mg + HCTZ mg + others**
After a one- to two-week placebo run-in period, patients entered a minimum four-year active treatment period. Active treatment continued for four years after the last patient was enrolled and until 1040 patients experienced a primary CV event.6
Losartan-based or atenolol-based antihypertensive therapy was titrated as shown in the slide to achieve a goal blood pressure (BP) reading of less than 140/90 mmHg. 6
Patients initially received losartan 50 mg or atenolol 50 mg once a day.6
After two months, HCTZ 12.5 mg was added if BP was not at or below goal.6
After four months, the dose of losartan or atenolol was doubled to 100 mg plus HCTZ 12.5 mg if BP was still inadequately controlled.6
At month 6, additional open-label antihypertensive medication including upward titration of HCTZ could be added in order to reach goal BP. The addition of ACE inhibitors, angiotensin II type 1 receptor antagonists, or beta-blockers was prohibited. If BP was >160/95 mmHg, upward titration was mandatory.6
Day
14
Day 7
Day 1
Mth 1
Mth 2
Mth 4
Mth 6 Yr 1 Yr
1.5 Yr 2 Yr
2.5 Yr 3 Yr
3.5 Yr 4 Yr 5
* Titration encouraged if SiDBP >90 mmHg or SiSBP >140 mmHg but was mandatory if SiBP >160 / 95 mmHg
**Other antihypertensives excluding ACEIs, AII antagonists, beta-blockers
HCTZ=hydrochlorothiazide, SiDBP= sitting diastolic blood pressure, SiSBP=sitting systolic blood pressure
Adapted from Dahlöf B et al Lancet 2002; 359:995–1003.

7. Trial Profile of Subpopulation
10,778 assessed for eligibility
1556 ineligible 1341 did not meet protocol criteria
215 were unwilling to participate
9222 randomized
29 excluded for irregularities at one center
342 with a history of AF at baseline
8851 study patients
Slide 7
In the LIFE study, a total of 10,778 patients were assessed for eligibility for entry into the trial.6 The inclusion criteria were: age 55 to 80 years, previously treated or untreated hypertension, systolic BP 160 to 200 mmHg and/or diastolic BP 95 to 115 mmHg, and ECG-documented LVH.6
Of those patients, 9222 were randomized to active treatment. A total of 8851 of these patients did not have ECG evidence of AF or a history of AF at baseline.5 Data from 4298 patients treated with losartan and 4182 treated with atenolol were available for analysis.5
Losartan group
4298 available for analysis
150 patients with new-onset AF
Atenolol group
4182 available for analysis
221 patients with new-onset AF
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:712–719. 7

8. Baseline Characteristics of Patients with New-Onset AF*
Losartan-based Atenolol-based Characteristics regimen (n =150) regimen (n = 221)
Age (years)
Women (%) 75 (50 ) 106 (48)
Systolic BP (mmHg)
Diastolic BP (mmHg)
ECG evidence of LVH
Cornell voltage-duration (mVms)
Sokolow-Lyon (mV)
Heart rate (beats/min)
Framingham risk (%)
Slide 8
This slide shows the baseline demographic and clinical characteristics of patients with new-onset AF randomized to losartan or atenolol. There were no significant differences in the clinical characteristics, medical history (not shown), or laboratory values (not shown) except that the urine albumin/creatinine (mg/mmol) was somewhat higher in the losartan group versus the atenolol group (16.2 ± 53.6 vs. 6.8 ± 16.1, respectively; p = 0.05).5
“There were no differences at baseline or during the study in concomitant treatment with class IA-IC or III antiarrhythmic drugs, digoxin, or non-dihydropyridine calcium channel blockers between losartan- and atenolol-treated patients (data not shown). However, atenolol-treated patients were more likely to receive anticoagulation therapy (5.3% vs. 7.7%, p< 0.001).”5
* AF was identified from yearly ECGs that underwent Minnesota coding for AF at one ECG core center.
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:712–719. 8

9. Losartan Significantly Reduced the Risk of New-Onset AF by 33%
HR: 0.67 [95% CI: 0.55–0.83], p<0.001
Adj HR: 0.67 [95% CI: 0.55–0.83], p<0.001 6 12 18 24 30 36 42 48 54 60 66 1 2 3 4 5 7 8
Time (months)
Proportion of patients
with first event (%)
Losartan group
Atenolol group
Slide 9
This slide shows Kaplan-Meier curves for new-onset AF verified by ECG during the follow-up of the study. The proportion of patients with AF is plotted against the time of follow-up in months. The stair-step look of the plot resulted from the definition of AF at the annual follow-up visit.
New-onset AF occurred in 150 of the patients on a losartan-based regimen and 221 of those on an atenolol-based regimen.5 The relative risk (RR) of having new-onset AF (expressed as the hazard ratio) was Thus, losartan versus atenolol treatment reduced the risk of new-onset AF by 33%.5 Adjustment for differences in LVH by Cornell voltage duration, Sokolow-Lyon criteria and Framingham risk score had only minimal effect on the reduction of new-onset AF associated with losartan.5
Patients treated with losartan tended to stay in sinus rhythm longer from baseline than did those treated with atenolol (1809 ± 225 vs ± 254, respectively; p = 0.057).5
HR = hazard ratio; CI = confidence interval
Adapted from Wachtell et al J Am Coll Cardiol 2005;45:712–719.

10. Fatal or Nonfatal stroke
Patients with New-Onset AF Had an Increased Risk of Cardiovascular Events
Ref 5, page 717, Table 3, lines 2-4, 6, 8-10
22.1%
15.4%
Percentage
10.7%
7.5%
6.7% 5%
Slide 10
4.2% 4%
This slide shows that patients with new-onset AF had an increased risk of cardiovascular events, irrespective of the treatment regimen. The percentage of patients with new-onset AF who met the composite endpoint criteria or the individual components was compared to that of patients who remained in sinus rhythm. The percentages were calculated by dividing the number of events by the number of patients.5 There were 371 patients with new-onset AF and 8480 patients who remained in sinus rhythm.5
Patients with new-onset AF had an approximate twofold higher increase in risk of reaching the composite endpoint (cardiovascular mortality, stroke, or MI) and an approximate threefold higher risk of developing fatal or nonfatal stroke.5
(n=82)
(n=911)
(n=28)
(n=352)
(n=57)
(n=428)
(n=25)
(n=342)
Composite endpoint
Cardiovascular
mortality
Fatal or Nonfatal stroke MI
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

11. Losartan- and Atenolol-Based Regimens Resulted in Similar BP Reductions in Patients with New-Onset AF
Losartan group Atenolol group (n=150) (n=221)
Baseline
Systolic
Diastolic
Reduction*,**
Systolic
Diastolic
* Mean + SD
** At end of follow-up or last visit before endpoint
SD = standard deviation
mmHg
Slide 11
This slide shows the mean baseline and mean reductions for systolic and diastolic BP in the patients with new-onset AF. There was no significant difference between the two treatment groups in either the baseline or the reductions in systolic or diastolic pressures.5
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

12. Study Summary
Patients with new-onset AF had an increased risk of cardiovascular events, irrespective of treatment regimen
Twofold increase in the risk of CV mortality
Threefold increase in the risk of fatal or nonfatal stroke
Losartan and atenolol provided similar BP reductions in patients with new-onset AF
A losartan-based regimen provided a 33% risk reduction in new-onset AF versus an atenolol-based regimen
Slide 12
Patients with new-onset AF had an increased risk of cardiovascular events, irrespective of treatment regimen
Twofold increase in the risk of CV mortality
Threefold increase in the risk of fatal or nonfatal stroke
Losartan and atenolol provided similar BP reductions in patients with new-onset AF
A losartan-based regimen provided a 33% risk reduction in new-onset AF versus an atenolol-based regimen
Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

13. Authors’ Conclusion
“…new-onset AF and subsequent stroke were significantly reduced by losartan- compared with atenolol-based antihypertensive treatment, with similar blood pressure reduction.”
Kristian Wachtell, et al.
Slide 13
“…new-onset AF and subsequent stroke were significantly reduced by losartan- compared with atenolol-based antihypertensive treatment, with similar blood pressure reduction.”
Kristina Wachtell, et al.
Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

14. Recently published in the Journal of the American College of Cardiology
Kristian Wachtell, Björn Hornestam, Mika Lehto, David J. Slotwiner, Eva Gerdts, Michael H. Olsen, Peter Aurup, Björn Dahlöf, Hans Ibsen, Stevo Julius, Sverre E. Kjeldsen, Lars H. Lindholm, Markku S. Nieminen, Jens Rokkedal, Richard B. Devereux
Cardiovascular Morbidity and Mortality in Hypertensive Patients with a History of Atrial Fibrillation: The LIFE Study
Slide 14
J Am Coll Cardiol 2005;45:705–711.

15. LIFE AF Substudy Design
342 hypertensive patients with LVH and ECG-documented AF or atrial flutter or history of AF
Random assignment to once-daily losartan or once-daily atenolol for a mean of 4.8 years
ECGs at baseline and at yearly follow-up
Slide 15
In the LIFE study, 9193 hypertensive patients and patients with electrocardiographic evidence of LVH were randomized to once-daily losartan- or atenolol-based antihypertensive therapy.6 ECGs were Minnesota coded centrally at a single core laboratory, and 342 patients with ECG-documented LVH and ECG-documented AF or atrial flutter or history of AF were followed for 4.8 ± 1.0 years. ECGs were obtained at baseline and at the yearly follow-up visits.7
Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

16. Baseline Demographics of Patients with History of AF
Patients on Losartan Patients on Atenolol Characteristics (n = 157) (n = 185)
Age (years)
Women — n (%) 64 (41 ) 84 (45.2)
Systolic BP (mmHg)
Diastolic BP (mmHg)
ECG evidence of LVH
Cornell voltage-duration (mVms)
Sokolow-Lyon (mV)
Heart rate (beats/min)
Framingham risk score
Current atrial fibrillation — n (%) (32.5) (34.6)
Slide 16
The demographics of the 342 patients who had AF or a history of AF at baseline were quite comparable in the two treatment groups.7
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711. 16

17. Proportion of patients
Losartan-Based Regimen Resulted in 42% Risk Reduction in the Primary Composite Endpoint* in Patients with a History of AF at Baseline
Losartan 50
HR: 0.58 (0.39–0.87), p=0.009
Adj HR: 0.58 (0.39–0.88), p=0.009
Atenolol 40 30
Proportion of patients
with first event 20 10
Slide 17
This slide shows Kaplan-Meier curves for the primary composite endpoint of the LIFE trial (cardiovascular death, stroke, or MI) in patients with a history of AF at baseline. The proportion of the patients who met the composite endpoint criteria is plotted against the time of follow-up in months.
Patients treated with a losartan-based regimen had a 42% reduced risk of the primary endpoint (HR = 0.58, 95% CI = 0.39–0.87, p=0.009).7 The HR did not change after adjustments for degree of LVH, ECG-documented AF, Framingham risk score, and treatment allocation.7 6 12 18 24 30 36 42 48 54 60 66 72
Time (months)
Number of Patients:
Losartan:
Atenolol:
* Composite endpoint was first occurrence of cardiovascular death, stroke, and MI.
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

18. Proportion of patients
Losartan-Based Regimen Resulted in a 45% Risk Reduction in Stroke in Patients with a History of AF 20
HR: 0.55 [0.31–0.97], p=0.038
Adj. HR: 0.58 [0.31–0.97], p=0.045 15
Proportion of patients
with first event (%) 10 5
Losartan
Slide 18
Atenolol
This slide shows Kaplan-Meier curves for the fatal or nonfatal stroke endpoint in patients with AF at baseline. The proportion of patients who met this endpoint is plotted against the time of follow-up in months.
Patients treated with losartan had a 45% reduced risk of stroke (HR = 0.55, 95% CI = 0.31–0.97, p=0.038).7 After adjustments for degree of LVH, ECG-documented AF, Framingham risk score, and treatment allocation, the HR was 0.58 (42%) (p = 0.045).7 6 12 18 24 30 36 42 48 54 60 66 72
Time (months)
Number of Patients:
Losartan:
Atenolol:
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

19. Proportion of patients
Losartan-Based Regimen Resulted in a 42% Risk Reduction in Cardiovascular Death in Patients with a History of AF
Losartan
Atenolol 30
HR: 0.58 [0.33–0.99], p=0.048
Adj. HR: 0.58 [0.33–0.99], p=0.045 20
Proportion of patients
with first event (%) 10
Slide 19
This slide shows Kaplan-Meier curves for cardiovascular death in patients with AF at baseline. The proportion of patients who died of cardiovascular causes is plotted against the time of follow-up in months.
Patients treated with losartan had a 42% reduced risk of cardiovascular death (HR = 0.58, 95% CI = 0.33–0.99, p = 0.048).7 The HR did not change after adjustments for degree of LVH, ECG-documented AF, Framingham risk score, and treatment allocation.7 6 12 18 24 30 36 42 48 54 60 66 72
Time (months)
Number of Patients:
Losartan:
Atenolol:
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

20. Proportion of patients
Losartan-Based Regimen Had No Significant Effect on the Risk of Myocardial Infarction 8
HR = 1.63, 95% CI = 0.65–4.04, p = 0.296
Adj. HR: 1.49 [0.60–3.72], p=0.392 7 6 5
Proportion of patients
with first event (%) 4 3 2
Losartan
Slide 20 1
Atenolol
This slide shows Kaplan-Meier curves for MI (fatal and nonfatal) in patients with AF at baseline. The proportion of patients who had a fatal or nonfatal MI is plotted against the time of follow-up in months.
Patients treated with losartan-based regimen had an apparent increase in risk of MI (HR = 1.63, 95% CI = 0.65–4.04, p = 0.296). This increase was not statistically significant; a total of 19 MI events were observed—11 with a losartan-based regimen and 8 with an atenolol-based regimen.
The p value increased after adjustments for degree of LVH, ECG-documented AF, Framingham risk score, and treatment allocation, but the difference was statistically less significant.7 6 12 18 24 30 36 42 48 54 60 66 72
Time (months)
Number of Patients:
Losartan:
Atenolol:
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

21. Proportion of patients
Losartan-Based Regimen Displayed a Nonsignificant Trend to Reduce the Risk of All-Cause Mortality 30
HR: 0.67 [0.42–1.05], p=0.079
Adj. HR: 0.67 [0.42–1.06], p=0.09 20
Proportion of patients
with first event (%) 10
Slide 21
Losartan
This slide shows Kaplan-Meier curves for all-cause mortality in patients with AF at baseline. The proportion of patients who died from all causes is plotted against the time of follow-up in months.
Patients treated with a losartan-based regimen displayed a nonsignificant trend for a reduced risk of all-cause mortality (HR = 0.67, 95% CI = 0.42–1.05, p = 0.079).7 There was little change in the HR after adjustments for degree of LVH, ECG-documented AF, Framingham risk score, and treatment allocation.7
Atenolol 6 12 18 24 30 36 42 48 54 60 66 72
Time (months)
Number of Patients:
Losartan:
Atenolol:
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

22. Losartan- and Atenolol-Based Regimen Resulted in Similar BP Reductions in Patients with a History of AF
180
Losartan
170
Atenolol
160
150
Systolic
140
130
BP (mmHg)
120
110
Mean Arterial
100
Slide 22
The losartan- and atenolol-based treatments resulted in similar substantial reductions in systolic, diastolic, and mean BPs.7 The average BP at the last visit before a primary endpoint, or at the end of follow-up, was 145/81 and 147/79 mm Hg in the losartan and atenolol groups, respectively, showing reductions of 31/17 and 26/16 mmHg, respectively.7 90 80
Diastolic 70 60 6 12 18 24 30 36 42 48 54
Study Month
Adapted from Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

23. Study Summary In hypertensive patients with LVH and a history of AF
Losartan- and atenolol-based regimens provided similar BP reductions
A losartan-based regimen was associated with a 42% risk reduction in the composite endpoint
Patients on a losartan-based regimen had a 42% risk reduction in cardiovascular death
A 45% risk reduction in stroke was observed in patients on a losartan-based regimen
Slide 23
In hypertensive patients with LVH and a history of AF
Losartan- and atenolol-based regimens provided similar BP reductions
A losartan-based regimen was associated with a 42% risk reduction in the composite endpoint
Patients on a losartan-based regimen had a 42% risk reduction in cardiovascular death
A 45% risk reduction in stroke was observed in patients on a losartan-based regimen
Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

24. Authors’ Conclusion
“Losartan-based antihypertensive therapy was more effective than an atenolol-based regimen in reducing the risk of the primary composite endpoint of CV morbidity and CV mortality as well as the secondary endpoints of stroke and CV death in hypertensive patients with ECG LVH and a history of AF.”
Kristian Wachtell, et al.
Slide 24
“Losartan-based antihypertensive therapy was more effective than an atenolol-based regimen in reducing the risk of the primary composite endpoint of CV morbidity and CV mortality as well as the secondary endpoints of stroke and CV death in hypertensive patients with ECG LVH and a history of AF.”
Kristian Wachtell, et al.
Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

25. Cardiac Pathology and Ischemic Stroke
LVH or atrial enlargement AF
Left atrial blood stasis and emboli formation
Slide 25
This slide shows how cardiac pathology (e.g., LVH or atrial enlargement) can lead to AF, which in turn can result in left atrial blood stasis, emboli formation, and ultimately stroke.3,8-10
Thrombotic or embolic event
Ischemic stroke
Vaziri SM et al Circulation 1994;89:724–730; Hart RG et al Ann Intern Med 2003;138:831–838; Fyrenius A et al Heart 2001;86:448–455; Shinokawa N et al Chest 2001;120:840–846.

26. Overall AF Risk Findings
AF increases cardiovascular morbidity and mortality and the risk of stroke in hypertensive patients with ECG-confirmed LVH.
Patients with new-onset AF have an approximate:
Twofold increased risk of cardiovascular events
Threefold increased risk of fatal or nonfatal stroke
Slide 26
AF increases cardiovascular morbidity and mortality and the risk of stroke in hypertensive patients with ECG-confirmed LVH.
Patients with new-onset AF have an approximate:
Twofold increased risk of cardiovascular events
Threefold increased risk of fatal or nonfatal stroke
Benjamin EJ et al Circulation 1998;98:946–952; Krahn AD et al Am J Med 1995;98:476–484;
Hart RG et al Ann Intern Med 2003;138:831–838; Straus SE et al JAMA 2002;288:1388–1395;
Wachtell K et al J Am Coll Cardiol 2005;45:712–719.

27. Overall Treatment Comparison: Losartan vs. Atenolol
In patients without AF at baseline, a losartan-based regimen provided a 33% risk reduction in new-onset AF versus an atenolol-based regimen
In patients with a history of AF at baseline, a losartan- versus an atenolol-based regimen was associated with:
42% risk reduction in the composite endpoint (cardiovascular death, stroke, or MI)
45% risk reduction in stroke
42% risk reduction in cardiovascular death
No significant differences in MI
These two studies provide the first documented evidence that one antihypertensive medication (a regimen based on losartan) was more effective than another (a regimen based on atenolol) in reducing the development of new-onset AF and in reducing CV morbidity and mortality in hypertensive patients with LVH and a history of AF, with comparable reductions in BP
Slide 27
In patients without AF at baseline, a losartan-based regimen provided a 33% risk reduction in new-onset AF versus an atenolol-based regimen
In patients with a history of AF at baseline, a losartan- versus an atenolol-based regimen was associated with:
42% risk reduction in the composite endpoint (cardiovascular death, stroke, or MI)
45% risk reduction in stroke
42% risk reduction in cardiovascular death
No significant differences in MI
These two studies provide the first documented evidence that one antihypertensive medication (a regimen based on losartan) was more effective than another (a regimen based on atenolol) in reducing the development of new-onset AF and in reducing CV morbidity and mortality in hypertensive patients with LVH and a history of AF, with comparable reductions in BP
Wachtell K et al J Am Coll Cardiol 2005;45:712–719; Wachtell K et al J Am Coll Cardiol 2005;45:705–711.

28. References References
Benjamin EJ, Wolf PA, D’Agostino RB et al. Impact of atrial fibrillation on the risk of death: The Framingham heart study. Circulation 1998;98:946–952.
Krahn AD, Manfreda J, Tate RB et al. The natural history of atrial fribrillation: Incidence, risk factors, and prognosis in the Manitoba follow-up study. Am J Med 1995;98:476–484.
Hart RG, Halperin JL, Pearce LA et al. Lessons from the stroke prevention in atrial fibrillation trials. Ann Intern Med 2003;138:831–838.
Straus SE, Majumdar Sr, McAlister FA. New evidence for stroke prevention. JAMA 2002;288:1388–1395.
Wachtell K, Lehto M, Gerdts E et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: The LIFE study. J Am Coll Cardiol 2005;45:712–719.
Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): A randomized trial against atenolol. Lancet 2002;359:995–1003.
Wachtell K, Hornestam B, Lehto M et al. Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The LIFE study. J Am Coll Cardiol 2005;45:705–711.
Vaziri SM, Larson MG, Benjamin EJ, Levy D. Echocardiographic predictors of nonrheumatic atrial fibrillation. The Framingham study. Circulation 1994;89:724–730.
Fyrenius A, Ebbersunt, Karlsson M et al. Three dimensional flow in the human left atrium. Heart 2001;86:448–455.
Shinokawa N, Hirai T, Takashima S et al. A transesophageal echocardiographic study on risk factors for stroke in elderly patients with atrial fibrillation. A comparison with younger patients. Chest 2001;120:840–846.

29. Atrial Fibrillation Findings in the LIFE Trial
Before prescribing, please consult the manufacturers’ prescribing information.
Merck does not recommend the use of any product in any different manner than as described in the prescribing information.
Slide 29
Before prescribing, please consult the manufacturers’ prescribing information.
Merck does not recommend the use of any product in any different manner than as described in the prescribing information.
Copyright © 2005 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved CZR 2005-W SC Printed in USA
VISIT US ON THE WORLD WIDE WEB AT
Copyright © 2005 Merck & Co., Inc., Whitehouse Station, NJ, USA.
All rights reserved CZR 2005-W SC Printed in USA
VISIT US ON THE WORLD WIDE WEB AT