1 ATRIAL FIBRILLATION AT BASELINE ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP AND DURING FOLLOW-UP in in The Antihypertensive and Lipid- The Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Lowering Treatment to Prevent Heart Attack Trial Attack Trial November 9, 2003 November 9, 2003 ALLHAT ALLHAT L. Julian Haywood, Charles E. Ford , Richard S. Crow, Barry R. Davis, Paula T. Einhorn, Angela Williard, and Barry Massie
ALLHAT. ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP in The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial November 9, 2003. L. Julian Haywood, Charles E. Ford , Richard S. Crow, Barry R. Davis, Paula T. Einhorn, Angela Williard, and Barry Massie. ALLHAT. - PowerPoint PPT Presentation
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ATRIAL FIBRILLATION AT BASELINEATRIAL FIBRILLATION AT BASELINEAND DURING FOLLOW-UPAND DURING FOLLOW-UP
ininThe Antihypertensive and Lipid-Lowering The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialTreatment to Prevent Heart Attack Trial
November 9, 2003November 9, 2003
ALLHATALLHAT
L. Julian Haywood, Charles E. Ford, Richard S. Crow, Barry R. Davis, Paula T. Einhorn, Angela Williard, and Barry Massie
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PurposePurpose
• To document the prevalence of atrial To document the prevalence of atrial fibrillation (AF) or atrial flutter (AFL) at fibrillation (AF) or atrial flutter (AFL) at baseline and its new appearance during baseline and its new appearance during follow-up in ALLHAT. follow-up in ALLHAT.
• To determine the influence of AF/AFL at To determine the influence of AF/AFL at baseline on outcome in ALLHAT. baseline on outcome in ALLHAT.
• Determined whether fatal CHD or nonfatal Determined whether fatal CHD or nonfatal MI was lower for high-risk hypertensives MI was lower for high-risk hypertensives treated with amlodipine (CCB), lisinopril treated with amlodipine (CCB), lisinopril (ACEI), doxazosin (alpha blocker) vs (ACEI), doxazosin (alpha blocker) vs chlorthalidone (diuretic)chlorthalidone (diuretic)
• Atrial fibrillation (AF) is the most common Atrial fibrillation (AF) is the most common serious arrhythmia affecting morbidity and serious arrhythmia affecting morbidity and mortality. mortality.
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ALLHATALLHAT MethodsMethods
• Standard 12-lead ECGs, recorded at baseline and Standard 12-lead ECGs, recorded at baseline and at 2-year intervals during follow-up, were coded at 2-year intervals during follow-up, were coded for Q-wave abnormalities, ST-segment for Q-wave abnormalities, ST-segment depression, T-wave inversion, LVH, bundle depression, T-wave inversion, LVH, bundle branch block, and atrial fibrillation or flutter, branch block, and atrial fibrillation or flutter, using the Minnesota Code.using the Minnesota Code.
• Univariate and multivariate statistical methods Univariate and multivariate statistical methods were used to determine prevalence, incidence, were used to determine prevalence, incidence, and prognosis as relates to multiple clinical and prognosis as relates to multiple clinical parameters, and according to treatment group.parameters, and according to treatment group.
Sample Size and Number (%) of Sample Size and Number (%) of Participants with AF,Participants with AF,
Excluding Doxazosin GroupExcluding Doxazosin Group
a. The doxazosin arm of ALLHAT was stopped in January 2000 due to higher CV events and virtually no chance to show a difference in CHD.b. Missing baseline ECG but one or more follow-up ECGs on file.c. Atrial fibrillation and flutter, combined.
Mean Serum Glucose, mg/dLMean Serum Glucose, mg/dL 117.6117.6 122.7122.7
Mean Cholesterol, mg/dLMean Cholesterol, mg/dL 204.8204.8 216.0 **216.0 **
Mean LDL-C, mg/dLMean LDL-C, mg/dL 129.7129.7 135.8 **135.8 **
Mean HDL-C, mg/dLMean HDL-C, mg/dL 43.943.9 46.8 **46.8 **
Mean Triglycerides, mg/dLMean Triglycerides, mg/dL 164.7164.7 176.4176.4
Mean BMI, kg/mMean BMI, kg/m22 29.829.8 29.729.7
Baseline Characteristics Stratified By Atrial Baseline Characteristics Stratified By Atrial
Fibrillation StatusFibrillation Status
* Indicates statistical significance of difference (p < 0.05).
** Indicates statistical significance of difference (p < 0.01).
ALLHATALLHAT
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ALLHATALLHAT
10.45 11.89 10.59
0
5
10
15
20
25
30
35
40
Chlorthalidone Amlodipine Lisinopril
Prevalence of Atrial Fibrillation Per 1000 Prevalence of Atrial Fibrillation Per 1000 Participants, by Randomized Treatment GroupParticipants, by Randomized Treatment Group
* Compared with chlorthalidone, neither the amlodipine nor lisinopril group differed significantly.
Eve
nts
per
100
0
AF prevalence was 10.9 per 1000, overall (334/30,704).
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ALLHATALLHAT
6.12 6.94 5.98
13.43*14.23*
30.43*
17.10*
0
5
10
15
20
25
30
35
40
55-69 70-79 80+ Women Men Black Non-Black
Prevalence of Atrial Fibrillation Per 1000 Prevalence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
* Subgroup differs significantly from comparison group (55-69, women, black) before and after adjusting for age, race, and sex (p < 0.01).
Age at Entry, yearsAge at Entry, years
Eve
nts
per
100
0
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ALLHATALLHAT
9.2411.78
14.96
9.4813.41
10.417.72
14.47*
0
5
10
15
20
25
30
35
40
Diabetic Non-Diabetic
CHD CHDAbsent
ECG LVH No LVH ASCVD NoASCVD
Prevalence of Atrial Fibrillation Per 1000 Prevalence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
* ASCVD subgroup differs significantly from comparison group (no ASCVD) before and after adjusting for age, race, and sex (p < 0.01).
Prevalence of Atrial Fibrillation Per 1000 Prevalence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
Subgroups do not differ significantly from comparison groups after adjustment for age, race, and sex differences.
Eve
nts
per
100
0
14
ALLHATALLHAT
Occurrence of New Atrial FibrillationOccurrence of New Atrial Fibrillation
Occurrence of Atrial Fibrillation Per 1000 Occurrence of Atrial Fibrillation Per 1000 Participants, by Randomized Treatment GroupParticipants, by Randomized Treatment Group
* Compared with chlorthalidone, neither the amlodipine nor lisinopril group differed significantly.
RR (95% CI) p value
A/C 1.07 (0.87-1.31) 0.53
L/C 0.95 (0.77-1.17) 0.64
Eve
nts
per
100
0 AF incidence was 17.2 per 1000, overall (551/32,042).
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ALLHATALLHAT
10.56
23.91*27.37*
11.30
20.75*
9.30
22.12*
0
5
10
15
20
25
30
35
40
Men Women Black Non-Black 55-69 70-79 80+
Occurrence of Atrial Fibrillation Per 1000 Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
Adj. RR (95% CI) p value
M/W 2.10 (1.74-2.54) < 0.001
NB/B 2.00 (1.61-2.48) < 0.001
70-79/55-69 2.39 (2.00-2.86) < 0.001
80+/55-69 2.38 (1.74-3.26) < 0.001
Eve
nts
per
100
0
Age, years
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13.7412.14
16.66
30.18*
22.00*25.68*
0
5
10
15
20
25
30
35
40
CHD No CHD ASCVD No ASCVD LVH No LVH
Occurrence of Atrial Fibrillation Per 1000 Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
Adj. RR (95% CI) p value
CHD 1.48 (1.23-1.76) < 0.001
ASCVD 1.42 (1.19-2.70) < 0.001
LVH 2.01 (1.47-2.77) < 0.001
Eve
nts
per
100
0
Left Ventricular Hypertrophy by ECG.
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ALLHATALLHAT
11.38
15.8 14.26
18.32*18.04*18.27*
0
5
10
15
20
25
30
35
40
Non-Smoker Smoker BMI>30 BMI<=30 K+<3.5 K+>=3.5
Occurrence of Atrial Fibrillation Per 1000 Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline CharacteristicsParticipants, by Baseline Characteristics
Adj. RR (95% CI) p value
Smoker 0.76 (0.60-0.97) 0.03
BMI>30 1.54 (1.29-1.84) < 0.001
K+ < 3.5 0.95 (0.62-1.47) < 0.001
Eve
nts
per
100
0
Serum potassium at 3-month visit.BMI = Body Mass Index
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ALLHATALLHAT
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
Cu
mu
lati
ve E
ven
t R
ate
0 1 2 3 4 5 6Years to Death
AF AbsentAF Absent
AF PresentAF Present
Cumulative Event Rates for All-Cause MortalityCumulative Event Rates for All-Cause Mortalityby Entry AF Statusby Entry AF Status
No AFNo AF 30,37030,370 28,95928,959 27,82927,829 26,64626,646 23,43323,433 13,62813,628 6,7956,795
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ALLHATALLHAT
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
Cu
mu
lati
ve E
ven
t R
ate
0 1 2 3 4 5 6Years to Death
ChlorthalidoneChlorthalidone
AmlodipineAmlodipine
LisinoprilLisinopril
Cumulative Event Rates for All-Cause MortalityCumulative Event Rates for All-Cause Mortalityin Those with AF at Entry, by Treatment Groupin Those with AF at Entry, by Treatment Group
RR (95% CI)RR (95% CI) p valuep value
A/CA/C 0.75 (0.48-1.160.75 (0.48-1.16 0.200.20
L/CL/C 0.71 (0.45-1.12)0.71 (0.45-1.12) 0.140.14
C:C: 147147 134134 122122 105105 8989 5757 3737
A:A: 9999 9595 8585 8080 6868 4141 2525
L:L: 8888 8484 8181 7575 6363 4040 1919
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ALLHATALLHAT Cumulative Event Rates for Fatal CHD or Nonfatal MICumulative Event Rates for Fatal CHD or Nonfatal MIin Those with AF, by Treatment Groupin Those with AF, by Treatment Group
0.00
0.05
0.10
0.15
0.20
Cu
mu
lati
ve E
ven
t R
ate
0 1 2 3 4 5 6
Years to Fatal CHD or Nonfatal MI
ChlorthalidoneChlorthalidone
AmlodipineAmlodipine
LisinoprilLisinopril
RR (95% CI)RR (95% CI) p valuep value
A/CA/C 0.62 (0.28-1.360.62 (0.28-1.36 0.240.24
L/CL/C 0.81 (0.39-1.70)0.81 (0.39-1.70) 0.580.58
C:C: 147147 129129 118118 100100 8484 4949 3232
A:A: 9999 9292 8181 7575 6363 3939 2424
L:L: 8888 8383 7979 7373 5959 3535 1818
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0.00
0.05
0.10
0.15
0.20
0.25
0.30
Cu
mu
lati
ve E
ven
t R
ate
0 1 2 3 4 5 6
Years to Stroke
Cumulative Event Rates for Stroke by Treatment Cumulative Event Rates for Stroke by Treatment Group In Participants with AF at BaselineGroup In Participants with AF at Baseline
ChlorthalidoneChlorthalidone
AmlodipineAmlodipine
LisinoprilLisinopril
RR (95% CI)RR (95% CI) p valuep value
A/CA/C 1.53 (0.79-2.971.53 (0.79-2.97 0.210.21
L/CL/C 1.10 (0.53-2.31)1.10 (0.53-2.31) 0.790.79
C:C: 147147 128128 117117 101101 8484 4949 3232
A:A: 9999 9191 8080 7171 6161 3434 1919
L:L: 8888 7979 7373 6868 5656 3535 1515
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Conclusion-1Conclusion-1
1.1. Prevalence of AF in ALLHAT at baseline Prevalence of AF in ALLHAT at baseline was increased by: age, non-Black status, was increased by: age, non-Black status, male gender, and presence of ASCVD. male gender, and presence of ASCVD.
2.2. AF at baseline was associated during AF at baseline was associated during follow-up with:follow-up with:
increased overall mortalityincreased overall mortalityincreased fatal CHD and MIincreased fatal CHD and MIincreased strokeincreased stroke
ALLHATALLHAT
In high-risk hypertensive patients :In high-risk hypertensive patients :
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Conclusion-2Conclusion-2
3.3. Likelihood of new onset of AF during follow-up Likelihood of new onset of AF during follow-up was increased by: Age, male gender, non-Black was increased by: Age, male gender, non-Black race, CHD, ASCVD, LVHrace, CHD, ASCVD, LVH
4.4. Randomization to chlorthalidone, amlodipine and Randomization to chlorthalidone, amlodipine and lisinopril did not influence prevalence of AF at lisinopril did not influence prevalence of AF at baseline or its new appearance during follow-up.baseline or its new appearance during follow-up.
5. Among participants with AF/AFL at baseline, there were no differences among randomized groups for mortality, major CHD events, or stroke.