1 ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP in The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial November 9, 2003.

Slides:

Advertisements

Similar presentations

U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute Review of Heart Failure Events in.

Advertisements

1 CAMELOT: Study Design A Morbidity and Mortality Study Patients with documented CAD on standard-of-care therapies* (n=1997) Clinical events (morbidity.

ALLHAT New Research Opportunities.

11/2/ Implications of ASCOT Results for ALLHAT Conclusions ALLHAT.

THE ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES STUDY (ACCORD)

1 SECOND AUSTRALIAN NATIONAL BLOOD PRESSURE STUDY (ANBP-2) Enalapril/ACEI vs. HCTZ, n = 6,083 Randomized, open-label (blinded endpoint review) All CV events.

Valsartan Antihypertensive Long-Term Use Evaluation Results

TROPHY TRial Of Preventing HYpertension. High-normal BP increases CV risk Vasan RS et al. N Engl J Med. 2001;345: Incidence of CV events in women.

Henry C. Ginsberg, MD College of Physicians & Surgeons, Columbia University, New York For The ACCORD Study Group.

The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) The LIPID Study Group N Engl J Med 1998;339:

Heart Failure With Preserved And Impaired Systolic Left Ventricular Function In ALLHAT JB Kostis, B Davis, L Simpson, H Black, W Cushman, P Einhorn, M.

U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute The Antihypertensive and Lipid-Lowering.

COURAGE: Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation Purpose To compare the efficacy of optimal medical therapy (OMT)

1 The JNC 7 recommendations for initial or combination drug therapy are based on sound scientific evidence.

Did Type of Prior Antihypertensive Therapy Influence the Heart Failure Results in ALLHAT? Richard Grimm, Barry Davis, Linda Piller, Karen Margolis, Joshua.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.

Lipid Lowering Substudy Trial of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial JAMA 2002;288: ALLHAT- LLT.

Results of Monotherapy in ALLHAT: On-treatment Analyses ALLHAT Outcomes for participants who received no step-up drugs.

Slide Source: Lipids Online Slide Library Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

1 Presenter Disclosure Information FINANCIAL DISCLOSURE: DSMB’s: Merck, Takeda Barry R. Davis, MD, PhD Clinical Outcomes in Participants with Dysmetabolic.

6 / 5 / RENAL DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED INTO 3 GROUPS BY BASELINE GLOMERULAR FILTRATION RATE (GFR) ALLHAT.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ALLHAT study overview Double-blind, randomized trial to determine whether.

Blood Pressure Control By Randomized Drug Group In ALLHAT William C. Cushman, Charles E. Ford, Paula T. Einhorn, Jackson T. Wright, Jr., Richard A. Preston,

Blood Pressure Control in Hispanics in the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Karen L. Margolis, Linda.

Success and Predictors of Blood Pressure Control in Diverse North American Settings: The Antihypertensive and Lipid- lowering Treatment to Prevent Heart.

Is It the Achieved Blood Pressure or Specific Medications that Make a Difference in Outcome, or Is the Question Moot? William C. Cushman, MD Professor,

Lecture 17 (Oct 28,2004)1 Lecture 17: Prevention of bias in RCTs Statistical/analytic issues in RCTs –Measures of effect –Precision/hypothesis testing.

1 U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute Major Outcomes in High Risk Hypertensive.

PPAR  activation Clinical evidence. Evolution of clinical evidence supporting PPAR  activation and beyond Surrogate outcomes studies Large.

1 Antihypertensive Trial Outcome Differences: Diuretic vs. Calcium Channel Blocker Compared to participants assigned to the diuretic, those assigned to.

1 Role of Diuretics in the Prevention of Heart Failure - The Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial ALLHAT Davis.

Morbidity and Mortality in Contemporary CAD Patients With Hypertension Treated With Either a Verapamil/Trandolapril or Beta-Blocker/Diuretic Strategy (INVEST):

HPS: Heart Protection Study Purpose To determine whether simvastatin reduces mortality and vascular events in patients with and without coronary disease,

Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension The First Outcomes Trial of Initial Therapy With.

Aim To determine the effects of a Coversyl- based blood pressure lowering regimen on the risk of recurrent stroke among patients with a history of stroke.

WOSCOPS: West Of Scotland Coronary Prevention Study Purpose To determine whether pravastatin reduces combined incidence of nonfatal MI and death due to.

1 Review of the Design and Initial Findings for Pre-specified Outcomes and Subgroups Paul K. Whelton, M.D., M.Sc. Loyola University Medical Center Maywood,

SPARCL Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial.

10/11/ Fasting Glucose Levels & Incident Diabetes Mellitus in Older Non-Diabetic Adults Randomized to Three Different Classes of Antihypertensive.

Heart Failure (HF) Findings: Are They Real? Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate.

U.S. Department of Health and Human Services National Institutes of Health National Heart, Lung, and Blood Institute ALLHAT Major Outcomes in Moderately.

VBWG PROactive: Study design Dormandy JA et al. Lancet. 2005;366: Charbonnel B et al. Diabetes Care. 2004;27: Objective: Assess the effects.

Naotsugu Oyama, MD, PhD, MBA A Trial of PLATelet inhibition and Patient Outcomes.

ALLHAT Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial JAMA 2002;288:

7/27/2006 Outcomes in Hypertensive Black and Nonblack Patients Treated with Chlorthalidone, Amlodipine, and Lisinopril* * Wright JT, Dunn JK, Cutler JA.

P Sever (Co-chair), B Dahlöf (Co-chair), N Poulter (Secretary), H Wedel (Statistician), G Beevers, M Caulfield, R Collins, SE Kjeldsen, A Kristinsson,

ALLHAT 6/5/ CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION RATE (3 GROUPS by GFR)

1 Pre-Specified Outcomes All primary and secondary outcomes and their components were pre-specified, i.e., they appeared in the protocol, manual of operations.

4S: Scandinavian Simvastatin Survival Study

Slide Source: Lipids Online Slide Library Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Design Sever PS et al. J Hypertens 2001;19:1139–1147.

VBWG Growth in heart disease, 2000–2050 Deaths Population Foot DK et al. J Am Coll Cardiol. 2000;35:

1 ALLHAT Antihypertensive Trial Results by Baseline Diabetic Status January 28, 2004.

6/5/ CARDIOVASCULAR DISEASE OUTCOMES IN HYPERTENSIVE PATIENTS STRATIFIED BY BASELINE GLOMERULAR FILTRATION RATE (4 GROUPS by GFR) ALLHAT.

Cardiovascular Outcomes in Hypertensives with CHD Randomized to Amlodipine versus Lisinopril in ALLHAT Frans Leenen MD, PhD, Chuke Nwachuku MA, MPH, Dr.

Saleem Jessani 1, Rasool Bux 1 and Tazeen H. Jafar 1,2. 1 Aga Khan University, Karachi, Pakistan 2 Duke-NUS Graduate Medical School, Singapore Socio-demographic.

A Randomized Trial of Intensive versus Standard Blood-Pressure Control The SPRINT Research Group* November 9, /NEJMoa R2 이성곤 /pf. 우종신.

Nephrology Journal Club The SPRINT Trial Parker Gregg

The ACCORD Trial: Review of Design and Results

*Imperial College London

Health and Human Services National Heart, Lung, and Blood Institute

Vanguard Phase Results for the Blood Pressure Component

All-cause mortality by treatment group

ALLHAT ALLHAT Antihypertensive Trial Results by Baseline Diabetic & Fasting Glucose Status.

The Anglo Scandinavian Cardiac Outcomes Trial

PS Sever, PM Rothwell, SC Howard, JE Dobson, B Dahlöf,

Determinants of new onset diabetes among hypertensive patients randomised in the ASCOT-BPLA Trial Dr Ajay K Gupta International Centre for Circulatory.

Health and Human Services National Heart, Lung, and Blood Institute

Post-Heart Failure Mortality

The following slides highlight a report by Dr

Baseline Lipid Parameters and Characteristics Among 3110 Men According to Quintiles of Total Cholesterol Ruben O. Halperin et al, Hypertension 2006;47;45-50.

Presentation transcript:

1 ATRIAL FIBRILLATION AT BASELINE AND DURING FOLLOW-UP in The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial November 9, 2003 ALLHAT L. Julian Haywood, Charles E. Ford, Richard S. Crow, Barry R. Davis, Paula T. Einhorn, Angela Williard, and Barry Massie

2Purpose To document the prevalence of atrial fibrillation (AF) or atrial flutter (AFL) at baseline and its new appearance during follow-up in ALLHAT.To document the prevalence of atrial fibrillation (AF) or atrial flutter (AFL) at baseline and its new appearance during follow-up in ALLHAT. To determine the influence of AF/AFL at baseline on outcome in ALLHAT.To determine the influence of AF/AFL at baseline on outcome in ALLHAT. ALLHAT

3ALLHAT Background Randomized, double-blind, multicenter trialRandomized, double-blind, multicenter trial Determined whether fatal CHD or nonfatal MI was lower for high-risk hypertensives treated with amlodipine (CCB), lisinopril (ACEI), doxazosin (alpha blocker) vs chlorthalidone (diuretic)Determined whether fatal CHD or nonfatal MI was lower for high-risk hypertensives treated with amlodipine (CCB), lisinopril (ACEI), doxazosin (alpha blocker) vs chlorthalidone (diuretic) Atrial fibrillation (AF) is the most common serious arrhythmia affecting morbidity and mortality.Atrial fibrillation (AF) is the most common serious arrhythmia affecting morbidity and mortality.

4

5ALLHAT Methods Standard 12-lead ECGs, recorded at baseline and at 2-year intervals during follow-up, were coded for Q-wave abnormalities, ST-segment depression, T-wave inversion, LVH, bundle branch block, and atrial fibrillation or flutter, using the Minnesota Code.Standard 12-lead ECGs, recorded at baseline and at 2-year intervals during follow-up, were coded for Q-wave abnormalities, ST-segment depression, T-wave inversion, LVH, bundle branch block, and atrial fibrillation or flutter, using the Minnesota Code. Univariate and multivariate statistical methods were used to determine prevalence, incidence, and prognosis as relates to multiple clinical parameters, and according to treatment group.Univariate and multivariate statistical methods were used to determine prevalence, incidence, and prognosis as relates to multiple clinical parameters, and according to treatment group.

6ALLHAT ChlorthalidoneAmlodipineLisinoprilDoxazosinTotal Sample Size15,2559,0489,0549,06142,418 No ECGs597(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 Flutter9(0.06)2(0.02)5(0.06)4(0.04)20 No AF or AFL13,915(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 Participants 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.

7ALLHAT ChlorthalidoneAmlodipineLisinoprilDoxazosin aTotal Sample Size15,2559,0489,0549,06133,357 No ECGs597(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 AFL13,915(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 Participants with AF, Excluding 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.

8AFPresentAFAbsent N33430,370 Mean age, y * Age 70+, % ** Black, % * Women, % ** Mean SBP Mean DBP Type 2 diabetes, % * History of CHD, % ** ECG LVH, % Cigarette Smokers, % ** Baseline Characteristics Stratified By Atrial Fibrillation Status * Indicates statistical significance of difference (p < 0.05). ** Indicates statistical significance of difference (p < 0.01). ALLHAT

9AFPresentAFAbsent N33430,370 On BP Medication, % With ASCVD, % ** Serum Creatinine >= 1.5, % Month Potassium < 3.5, % Mean Serum Glucose, mg/dL Mean Cholesterol, mg/dL ** Mean LDL-C, mg/dL ** Mean HDL-C, mg/dL ** Mean Triglycerides, mg/dL Mean BMI, kg/m Baseline Characteristics Stratified By Atrial Fibrillation Status * Indicates statistical significance of difference (p < 0.05). ** Indicates statistical significance of difference (p < 0.01). ALLHAT

10ALLHAT Prevalence of Atrial Fibrillation Per 1000 Participants, by Randomized Treatment Group * Compared with chlorthalidone, neither the amlodipine nor lisinopril group differed significantly. Events per 1000 AF prevalence was 10.9 per 1000, overall (334/30,704).

11ALLHAT Prevalence of Atrial Fibrillation Per 1000 Participants, 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, years Events per 1000

12ALLHAT Prevalence of Atrial Fibrillation Per 1000 Participants, by Baseline Characteristics * ASCVD subgroup differs significantly from comparison group (no ASCVD) before and after adjusting for age, race, and sex (p < 0.01). Events per 1000

13ALLHAT Prevalence of Atrial Fibrillation Per 1000 Participants, by Baseline Characteristics Subgroups do not differ significantly from comparison groups after adjustment for age, race, and sex differences. Events per 1000

14ALLHAT Occurrence of New Atrial Fibrillation Chlorthalidone n % n %Amlodipine Lisinopril Total Unknown , Negative 14, , , , AF Flutter Total 15, , , ,357--

15ALLHAT Occurrence of Atrial Fibrillation Per 1000 Participants, by Randomized Treatment Group * Compared with chlorthalidone, neither the amlodipine nor lisinopril group differed significantly. RR (95% CI) p value A/C1.07 ( )0.53 L/C0.95 ( )0.64 Events per 1000 AF incidence was 17.2 per 1000, overall (551/32,042).

16ALLHAT Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline Characteristics Adj. RR (95% CI) p value M/W2.10 ( )< NB/B2.00 ( )< / ( )< / ( )< Events per 1000 Age, years

17ALLHAT Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline Characteristics Adj. RR (95% CI) p value CHD1.48 ( )< ASCVD1.42 ( )< LVH2.01 ( )< Events per 1000 Left Ventricular Hypertrophy by ECG.

18ALLHAT Occurrence of Atrial Fibrillation Per 1000 Participants, by Baseline Characteristics Adj. RR (95% CI) p value Smoker0.76 ( ) 0.03 BMI> ( )< K+ < ( )< Events per 1000 Serum potassium at 3-month visit.BMI = Body Mass Index

19ALLHAT Cumulative Event Rate Years to Death AF Absent AF Present Cumulative Event Rates for All-Cause Mortality by Entry AF Status RR (95% CI) p value AF/Not 2.86 ( ) < AF No AF 30,37029,76429,06328,165 25,126 25,126 14,851 14,8517,439

20ALLHAT Cumulative Event Rate Years to Fatal CHD or Nonfatal MI Cumulative Event Rates for Fatal CHD or Nonfatal MI, by Entry AF Status AF Present AF Absent RR (95% CI) p value AF/Not 1.61 ( ) < 0.01 AF No AF 30,37028,85227,57626,248 22,939 22,939 13,250 13,2506,502

21ALLHAT Cumulative Event Rate Years to Stroke Cumulative Event Rates for Stroke by Entry AF Status AF Present AF Absent RR (95% CI) p value AF/Not 3.61 ( ) < AF No AF 30,37028,95927,82926,646 23,433 23,433 13,628 13,6286,795

22ALLHAT Cumulative Event Rate Years to Death Chlorthalidone Amlodipine Lisinopril Cumulative Event Rates for All-Cause Mortality in Those with AF at Entry, by Treatment Group RR (95% CI) p value A/C 0.75 ( L/C 0.71 ( ) 0.14 C: A: L:

23ALLHAT Cumulative Event Rates for Fatal CHD or Nonfatal MI in Those with AF, by Treatment Group Cumulative Event Rate Years to Fatal CHD or Nonfatal MI Chlorthalidone Amlodipine Lisinopril RR (95% CI) p value A/C 0.62 ( L/C 0.81 ( ) 0.58 C: A: L:

24ALLHAT Cumulative Event Rate Years to Stroke Cumulative Event Rates for Stroke by Treatment Group In Participants with AF at Baseline Chlorthalidone Amlodipine Lisinopril RR (95% CI) p value A/C 1.53 ( L/C 1.10 ( ) 0.79 C: A: L:

25Conclusion-1 1.Prevalence of AF in ALLHAT at baseline was increased by: age, non-Black status, male gender, and presence of ASCVD. 2.AF at baseline was associated during follow-up with: increased overall mortality increased fatal CHD and MI increased stroke ALLHAT In high-risk hypertensive patients :

26Conclusion-2 3.Likelihood of new onset of AF during follow-up was increased by: Age, male gender, non-Black race, CHD, ASCVD, LVH 4.Randomization to chlorthalidone, amlodipine and lisinopril did not influence prevalence of AF at 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. ALLHAT

27 Thank You