1 ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP in The Antihypertensive and Lipid-Lowering...

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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.

ALLHATALLHAT

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ALLHATALLHAT BackgroundBackground

• Randomized, double-blind, multicenter Randomized, double-blind, multicenter trialtrial

• 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.

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ALLHATALLHAT

ChlorthalidoneChlorthalidone AmlodipineAmlodipine LisinoprilLisinopril DoxazosinDoxazosin TotalTotal

Sample Size 15,255 9,048 9,054 9,061 42,418

No ECGs 597 (3.9) 311 (3.4)350

(3.9)369 (4.1) 1,627

No Baseline ECG a 596 (3.9) 409 (4.5)

390(4.3)

340 (3.8) 1,735

Atrial Fibrillation

138 (0.9) 97 (1.1)83

(0.9)85 (0.9) 403

Atrial Flutter 9 (0.06)2

(0.02)5

(0.06)4

(0.04)20

No AF or AFL 13,915 (91.2) 8,229 (90.9)8,226

(90.9)8,263 (91.2) 38,633

Total with Baseline ECG b 14,062 (92.2) 8,328 (92.0)

8,314(91.8)

8,352 (92.2) 39,056

Sample Size and Number (%) of Sample Size and Number (%) of Participants with AFParticipants with AF

a. Missing a baseline ECG, but with one or more follow-up ECGs on file.b. Sample size less those with no ECGs and no baseline ECG.

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ALLHATALLHAT

ChlorthalidoneChlorthalidone AmlodipineAmlodipine LisinoprilLisinopril Doxazosin a TotalTotal

Sample Size 15,255 9,048 9,054 9,061 33,357

No ECGs 597 (3.9) 311 (3.4) 350 (3.9) 369 (4.1) 1,258

No Baseline ECG b 596 (3.9) 409 (4.5) 390 (4.3) 340 (3.8) 1,395

AF c 147 (0.9) 99 (1.1) 88 (0.9) 89 (0.9) 334

No AF or AFL 13,915 (91.2) 8,229 (90.9) 8,226 (90.9) 8,263 (91.2) 30,370

Total with Baseline ECG

14,062 (92.2) 8,328 (92.0) 8,314 (91.8) 8,352 (92.2) 30,704

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.

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AFAFPresentPresent

AFAFAbsentAbsent

NN 334334 30,37030,370

Mean age, yMean age, y 72.172.1 66.9 *66.9 *

Age 70+, %Age 70+, % 63.863.8 35.3 **35.3 **

Black, %Black, % 18.918.9 34.5 *34.5 *

Women, %Women, % 29.329.3 46.2 **46.2 **

Mean SBPMean SBP 144.1144.1 144.8144.8

Mean DBPMean DBP 83.083.0 83.383.3

Type 2 diabetes, %Type 2 diabetes, % 30.230.2 35.7 *35.7 *

History of CHD, %History of CHD, % 35.035.0 25.4 **25.4 **

ECG LVH, %ECG LVH, % 6.66.6 5.25.2

Cigarette Smokers, %Cigarette Smokers, % 13.813.8 22.0 **22.0 **

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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AFAFPresentPresent

AFAFAbsentAbsent

NN 334334 30,37030,370

On BP Medication, %On BP Medication, % 91.691.6 90.290.2

With ASCVD, %With ASCVD, % 62.362.3 46.6 **46.6 **

Serum Creatinine >= 1.5, %Serum Creatinine >= 1.5, % 7.37.3 6.46.4

3-Month Potassium < 3.5, %3-Month Potassium < 3.5, % 6.96.9 6.06.0

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

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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


* ASCVD subgroup differs significantly from comparison group (no ASCVD) before and after adjusting for age, race, and sex (p < 0.01).

Eve

nts

per

100

0

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ALLHATALLHAT

6.85

12.01 11.42 10.3712.61

10.92 12.07 10.53

0

5

10

15

20

25

30

35

40

Smoker Non-Smoker

BMI 30+ BMI < 30 Cr >= 1.5 Cr < 1.5 K+ < 3.5 K+ >= 3.5


Subgroups do not differ significantly from comparison groups after adjustment for age, race, and sex differences.

Eve

nts

per

100

0

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ALLHATALLHAT

Occurrence of New Atrial FibrillationOccurrence of New Atrial Fibrillation

ChlorthalidoneChlorthalidone

n %n %

AmlodipineAmlodipine

n %n %

LisinoprilLisinopril

n %n %

TotalTotal

n %n %

UnknownUnknown 625625 4.14.1 328328 3.63.6 362362 4.04.0 1,3151,315 3.93.9

NegativeNegative 14,38614,386 94.394.3 8,5658,565 94.794.7 8,5548,554 94.594.5 31,50531,505 94.494.4

AFAF 230230 1.51.5 145145 1.61.6 130130 1.41.4 505505 1.51.5

FlutterFlutter 2828 0.20.2 1010 0.10.1 88 0.10.1 4646 0.10.1

TotalTotal 15,25515,255 ---- 9,0489,048 ---- 9,0549,054 ---- 33,35733,357 ----

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16.7 17.815.9

0

5

10

15

20

25

30

35

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Chlorthalidone Amlodipine Lisinopril

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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ALLHATALLHAT

13.7412.14

16.66

30.18*

22.00*25.68*

0

5

10

15

20

25

30

35

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CHD No CHD ASCVD No ASCVD LVH No LVH



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



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

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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

RR (95% CI)RR (95% CI) p valuep value

AF/NotAF/Not 2.86 (2.38-3.43)2.86 (2.38-3.43) < 0.001< 0.001

AFAF 334334 313313 288288 260260 220220 138138 8181

No AFNo AF 30,37030,370 29,76429,764 29,06329,063 28,16528,165 25,12625,126 14,85114,851 7,4397,439

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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

Cumulative Event Rates for Fatal CHD or Cumulative Event Rates for Fatal CHD or Nonfatal MI, by Entry AF StatusNonfatal MI, by Entry AF Status


AF AbsentAF Absent


AF/NotAF/Not 1.61 (1.20-2.17)1.61 (1.20-2.17) < 0.01< 0.01

AFAF 334334 304304 278278 248248 206206 123123 7474

No AFNo AF 30,37030,370 28,85228,852 27,57627,576 26,24826,248 22,93922,939 13,25013,250 6,5026,502

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ALLHATALLHAT

0.00

0.03

0.05

0.07

0.10

0.13

0.15

0.17

0.20

Cu

mu

lati

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ven

t R

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0 1 2 3 4 5 6Years to Stroke

Cumulative Event Rates for StrokeCumulative Event Rates for Strokeby Entry AF Statusby Entry AF Status


AF AbsentAF Absent


AF/NotAF/Not 3.61 (2.70-4.83)3.61 (2.70-4.83) < 0.001< 0.001

AFAF 334334 298298 270270 240240 201201 118118 6666

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

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0 1 2 3 4 5 6Years to Death




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


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

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ven

t R

ate

0 1 2 3 4 5 6

Years to Fatal CHD or Nonfatal MI





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

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ven

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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





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.

ALLHATALLHAT

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Thank YouThank You

1 ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP in The Antihypertensive and Lipid-Lowering...

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