Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks

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1 Treating Heart Failure in Biodiverse Patient Populations: Best Practices and Unveiling Disparities in Blacks 12th Annual Leadership Summit on Health Disparities & Congressional Black Caucus Spring Health Braintrust April 20-21, 2015 Keith C. Ferdinand, MD, FACC, FAHA,FASH,FNLA Professor of Clinical Medicine Tulane University School of Medicine Immediate Past-chair National Forum for Heart Disease and Stroke Prevention

2 Keith C. Ferdinand, MD Has disclosed the following affiliations. Any real or apparent COIs related to the presentation have been resolved. Speaker s Bureau -None Grant/Research Support -Boehringer Ingelheim Consultant -Astra Zeneca, Amgen,Sanofi, Boehringer Ingelheim

3 Heart Failure(HF): A Major Public Health Burden in the United States ~550,000 new cases of HF diagnosed each year prevalence, 8 million US adults >18 years of age (2.8%) had HF In the US, HF affects about 3% of the African American population; whereas, this rate is about 2% in the general population 2 The annual rates per 1000 population of new and recurrent HF events is: 3 Age (years) Black men Black women years of age years of age Go AS, et al. AHA Heart Disease and Stroke Statistics 2014 Update. Circulation. 2014;129:e28 e Yancy CW. J Card Fail. 2000;6: Thom T et al. Circulation. 2006;113:e85-e151.

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5 Projected HF: Race/ethnicity Heidenreich, Albert,NM et al Circ Heart Fail. 2013;6:00-00

6 Båibbins-Domingo et al. N Engl J Med. 2009;360:

7 Incident HF White and Black Men /Women in the CARDIA Study. N=5115 B vs. W P=0.001 Bibbins-Domingo K et al. N Engl J Med 2009;360:

8 Average reduction in events (%) Long-term Antihypertensive Therapy Significantly Reduces CV Events 0 Stroke Myocardial infarction Heart failure %-25% %-40% n=201,566 >50% Blood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2000;355:

9 Heart Failure: Causal Mechanisms Smoking Dyslipidemia Diabetes MI Systolic Dysfunction Hypertension HF Obesity Diabetes LVH Diastolic Dysfunction Normal LV Structure and Function LV Remodeling Subclinical LV Dysfunction Overt Heart Failure ACC/AHA Stage A Stage B Stage C Vasan RS and Levy D. Arch Int Med.1996;153:

10 Diastolic Heart Failure: More Common in African Americans Normal Diastolic Heart Failure Systolic Heart Failure Aurigemma GP et al. Circulation. 2006;113:

11 Etiology of Heart Failure in African American Patients Hypertension Coronary Artery Disease LVH MI HF More common cause of HF cases in blacks More common cause of HF cases in whites LVH=left ventricular hypertrophy HF=heart failure MI=myocardial infarction Adapted from Yancy CW. J Card Fail. 2003;9:S210-S215.

12 Manifestations of Heart Failure in African American Patients Prevalence of HF higher in African Americans than in Caucasians HF has a more malignant natural history in African American patients Occurs at an earlier age 1 Associated with more advanced LV disease at diagnosis 1 Differing etiology in African Americans More likely to be associated with a history of hypertension 1 Incidence of MI is consistently lower 1 Worse prognosis in African Americans Higher rate of hospitalization than in Caucasian patients 2 Higher mortality rate than in Caucasians 2 1. Yancy CW. J Card Fail. 2000;6: Yancy CW. J Card Fail. 2003;9:S210-S215.

13 Patients (%) Patients (%) Etiology of HF in African Americans V-HeFT 1 n=6421 V-HeFT II n=804 2 SOLVD n=2,569 3 US Carv n=1,094 4 BEST n=2,708 5 MERIT HF n=3,991 6 HF predominately caused by CAD V-HeFT I 1 V-HeFT II 2 SOLVD 3 US Carv 4 BEST 5 MERIT-HF 6 HF predominately caused by HTN V-HeFT I 1 V-HeFT II 2 SOLVD 3 US Carv 4 BEST 5 MERIT-HF 6 African American Non-African American 1 Cohn JN et al. N Engl J Med. 1986;314: Cohn JN et al. N Engl J Med. 1991;325: The SOLVD Investigators. N Engl J Med. 1991;325: Packer M et al. N Engl J Med. 1996;334: The BEST Investigators. N Engl J Med. 2001;344: MERIT-HF Study Group. Lancet. 1999;353:

14 Hypertension in African Americans Potential Physiologic and Hemodynamic Determinants Higher salt sensitivity Low levels of plasma renin 2 Vascular dysfunction vasoconstrictor hyperactivity diminished vasodilatory function Greater rates of comorbidity (especially diabetes mellitus) Obesity Sedentary lifestyle Unhealthy diet Family history 1. Nesbitt SD. Curr Hypertens Rep 2005;7: Gadegbeku CA et al. Med Clin North Am. 2005;89: Profant J et al. Hypertension.1999;33:

15 Joynt KE et al. JAMA. 2011;305:

16 Blacks and Minority Hospitals Higher HF Readmissions A Medicare Population Joynt KE et al. JAMA. 2011;305:

17 Hospital Readmission by Race/Ethnicity For HF, blacks have higher odds of readmission regardless of site of care While patients from minority-serving hospitals had even higher odds of readmissions regardless of race In general, whites at non-minority-serving hospitals had lowest risk of readmission Joynt KE et al. JAMA. 2011;305:

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19 ACC/AHA 2013 Heart Failure Guideline Recognition and Treatment of Elevated Blood Pressure Hypertension may be the single most important modifiable risk factor for HF in the US Hypertensive men and women have substantially greater risk for developing HF than normotensive men and women Yancy CW et al. J Am Coll Cardiol. 2013;62:e147-e239.

20 J Am Coll Cardiol. 2013;62(16):e147-e239. doi: /j.jacc

21 BEST : No Survival Advantage with -blocker Bucindolol in African Americans with HF Favors -blockade BEST African Americans BEST Non- African Americans (N=627) (N=2081) Non-African Americans African Americans Relative risk of mortality Shekelle PG et al. J Am Coll Cardiol. 2003;41:

22 Heart Failure is Associated with Neurohormonal Excess and Nitric Oxide Insufficiency Neurohormones Endothelial Nitric Oxide Neurohormonal Antagonists Beta Blockers Renin-Angiotensin Antagonists Aldosterone Blockers Nitric Oxide Enhancers (NOE) Fixed-dose combination Hyd/ISDN

23 Oxidative Stress Leads to a Nitroso-Redox Imbalance in Heart Failure Isosorbide dinitrate Stimulation Nitric oxide synthase Citrulline Oxidase Hydralazine Inhibition L-Arginine NO O 2 O 2 O 2 Physiologi c pathway Pathologi c pathway Formation of cyclic guanosine monophosphate Peroxynitrite (ONOO ) DNA damage S-nitrosylation: post-translational modification of effector molecules Hare JM. N Engl J Med. 2004;351: Inhibition Oxidized proteins Cell damage

24 Survival, % Survival, % Survival in Black Patients and White Patients V-HeFT I 100 Black patients 100 White patients ISDN/HYD Placebo HR = 0.53 (0.29, 0.98) P = HR = 0.88 (0.63, 1.24) P = Patients, n Time, days since randomization ISDN/HYD Placebo Cohn JN et al. N Engl J Med. 1986;314:

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26 A-HeFT Trial Objective Demonstrate the safety and efficacy of ISDN/HYD compared with placebo in African American patients with moderate to severe HF concurrently receiving standard HF treatment Inclusion Criteria Patients self-identified as African American NYHA class III or IV HF (> 3 months) LVEF < 35% (or < 45% with dilated LV by echo) Standard therapy for HF, including ACEI/ARB + BB (> 3 months)

27 Survival (%) A-HeFT: All-Cause Mortality 100 Fixed-dose Hydralazine/Isosorbide Dinitrate Hazard ratio=.57 P=.01 Placebo 43% Decrease Days Since Baseline Visit Date Fixed-dose I/H Placebo Taylor AL et al. N Engl J Med. 2004;351:

28 Without hospitalization, % Hydralazine/Isosorbide Dinitrate Fixed Dose Combination: Decreased Relative Risk of First HF Hospitalization by 39% HYD/ISDN FDC 80 Placebo HR = 0.61 (0.46, 0.80) P < Time since baseline visit date, days Patients at risk, n BiDil Placebo Taylor AL et al. N Engl J Med. 2004;351:

29 AHeFT: Trial Summary N=1050 All-Cause Mortality (%) First HF Hospitalization (%) Patient Reported Functional Status n= n= n= n= n=518 n=532 0 P= P< P<0.01 HYD/ISDN + Standard Therapies Placebo + Standard Therapies Taylor AL et al. N Engl J Med. 2004;351:2052.

30 2013 ACC/AHA Guideline: HYD and ISDN I IIa IIb III The combination of HYD and ISDN is recommended for African Americans with NYHA class III IV HFrEF on GDMT IA I IIa IIb III A combination of HYD and ISDN can be useful with HFrEF who cannot be given ACE-Is or ARBs IIa B Yancy CW, Jessup M, et al, JACC (2013)

31 Ivabradine FDA Approved April 15,2015 Funny current inhibitor for the treatment of heart failure Additional agent for blacks?

32 Conclusions HF disparities in by race and ethnicity Start early Persist May worsen Are preventable New guidelines and evidence-based best practices to improve outcomes and may help eliminate disparities in HF morbidity and mortality

33 Thank You!

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