heart failure treatment in african american patients

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Heart Failure Treatment in African

American Patients

Theresa Kline, PharmD & Lauren Kemp, PharmD

University of North Carolina Medical Center

Residency Program Director: Ian B. Hollis, PharmD, BCPS-AQ Cardiology

December 5, 2019

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Disclosures

• We have no disclosures to report

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Objectives

• Understand how heart failure etiology and pathophysiology differ in African

American patients versus Caucasian patients

• Analyze the literature for heart failure with reduced ejection fraction (HFrEF)

guideline directed therapies with respect to African American (AA) representation

• Evaluate new literature regarding novel HFrEF therapies and how to apply these

in African American patients

• Design an individualized treatment plan for African American patients with HFrEF

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Patient Case: Scenario 1

• MS is a 57 year old African American female that presents with complaints of

worsening shortness of breath and fatigue for 2 weeks. Symptoms noticeably

worsened after enjoying Thanksgiving dinner with her family.

• PMH: HTN, T2DM, GERD

• Home medications: hydrochlorothiazide 25 mg daily, metformin 1000 mg BID,

atorvastatin 40 mg daily, famotidine 20 mg daily PRN

• Vitals: HR 98, BP 146/92, RR 22, oxygen saturation 94%

• Imaging: Echo 30-35%, Chest x-ray unremarkable, EKG normal sinus rhythm

• Labs: WBC 5.0, HgB 11.8, PLT 202, Na 136, K 4.3, Mg 1.9, Scr 1.1, BUN 22,

Troponin <0.034, Pro-BNP 2034 pg/mL, A1C 7.4%

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• MS is diagnosed with HFrEF and treated with IV diuretics

• After 48 hours of IV diuresis, MS is ready to transition to oral diuretics and

begin medication optimization.

• 12/5/2019:


• Labs: WBC 5.0, HgB 11.7, PLT 197, Na 138, K 4.0, Mg 1.9, Scr 0.80, BUN 20

• In addition to stopping hydrochlorothiazide, what medication changes do you

want to make before discharge?• A: Start metoprolol tartrate and lisinopril

• B: Start metoprolol succinate and spironolactone

• C: Start carvedilol and lisinopril

• D: Start carvedilol and hydralazine/isosorbide dinitrate

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Objectives








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Epidemiology

• African Americans with HFrEF are considered a “high-risk” population

• Relative incidence 50% higher than the general population

• African American men: 1.8-fold increased mortality

• African American women: 2.4-fold increased mortality

Earlier ageNon-ischemic >

Ischemic

Increased

severity of LV

dysfunction

Faster

progression

Increased

hospitalizations

Increased

mortality

Franciosa JA. Congest Heart Fail. 2010;16(1):27-38

Yancy CW. J Natl Med Assoc. 2003;95(1):1-9

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Epidemiology

• Differences in outcomes are NOT solely due to socioeconomic factors • Multivariate analysis of SOLVD (Studies of Left Ventricular Dysfunction) prevention and treatment trials

after adjustment for education and financial distress:


Dries DL. N Engl J Med. 1999;340(8):609-16.

HFrEF Etiology Pathophysiology

OutcomeRelative Risk in African Americans

(95% CI)P-value

Death from all cause 1.28 (1.08 – 1.51) P=0.004

Death from pump failure 1.38 (1.08 – 1.76) P=0.009

Death from any cause or

hospitalization for heart failure 1.37 (1.20 – 1.57) P<0.001

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Neurohormonal Pathways

Renin-Angiotensin-

Aldosterone

System (RAAS)

Sympathetic

Nervous System

(SNS)

Nitric Oxide (NO)

Pathway

Natriuretic

Peptides

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Pathophysiology: RAAS System

• RAAS: Renin – Angiotensin –

Aldosterone System • Vasoconstriction

• Sodium and water retention

• African Americans are less affected by

RAAS inhibition• Lower levels of plasma renin activity

• African Americans have higher levels of transforming growth factor-β1 (TGF-β1)


Image adapted from https://neoreviews.aappublications.org/content/16/10/e575

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Pathophysiology: SNS System

• Sympathetic Nervous System (SNS)• Increased heart rate and workload of heart leads to cardiac remodeling

• African Americans have decreased β-adrenergic receptor sensitivity and lower

norepinephrine levels • Genetic polymorphisms: glycine substituted for arginine at position 389


Image adapted from https://www.medscape.com/viewarticle/463477

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Pathophysiology: Nitric Oxide Pathway

• Nitric oxide (NO) leads to vasodilation

and inhibition of vascular smooth

muscle hypertrophy

• African Americans are less responsive

to nitric oxide• Decreased production of NO

• Decreased NO bioavailability

• Endothelial dysfunction and hypertrophy

Echols MR. Vasc Health Risk Manag. 2006;2(4):423-31.


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Objectives




guideline directed therapies with respect to African American (AA)

representation




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Pharmacotherapy

Beta blockers

Angiotensin converting enzyme inhibitors/aldosterone receptor

blockers

Hydralazine/isosorbide dinitrate

Angiotensin receptor-neprilysin inhibitor

Aldosterone receptor antagonists

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Current Guidelines

Yancy CW. Circulation. 2017;136:e137–e161.

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Primary Literature Revisited

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African American Representation in Heart Failure Trials

1

2.5

3.6

5

5

5.1

7

7

20

27

28.5

100

0 10 20 30 40 50 60 70 80 90 100

EPHESUS

EMPHASIS-HF

CHARM

COPERNICUS

MERIT-HF

PARADIGM-HF

RALES

VAL-HeFT

US-Carvedilol

V-HeFT2

V-HeFT1

A-HeFT

Percent

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Guess that heart failure therapy

Shekelle PG. J Am Coll Cardiol. 2003;41(9):1529-38.

Relative Risk of All-Cause Mortality

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Guess that heart failure therapy

Relative Risk of All-Cause Mortality

in African Americans


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Beta Blockers

• Overall survival benefit demonstrated in HFrEF for all patients

• No significant difference in mortality detected in self-identified black patients

• Wide confidence intervals due to low enrollment


Packer M. Circulation. 2002;106(17):2194-9.

Merit-HF Study Group. Lancet. 1999;353(9169):2001-7.

Packer M. N Engl J Med. 1996;334(21):1349-55.

Trial Beta BlockerTotal

N% Black

RR White

(95% CI)

RR Black

(95% CI)

RR Overall

(95% CI)NNT

COPERNICUS Carvedilol 2,287 5.3% 0.66 (0.53-0.82) 0.62 (0.19-2.01) 0.65 (0.52-0.81) 15

US Carvedilol

HF TrialsCarvedilol 1,094 19.8% 0.38 (0.20-0.70) 0.53 (0.19-1.48) 0.35 (0.20-0.61) 22

MERIT-HFMetoprolol

succinate3,991 5.2% 0.67 (0.54-0.82) 0.79 (0.36-1.76) 0.66 (0.53-0.81) 27

CIBIS-II Bisoprolol 2647Not

reported-- -- 0.66 (0.54-0.81) 19

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Beta Blockers

• Overall benefit in targeting the SNS in African Americans• Carvedilol:

– Decreased combined endpoint of mortality plus all cause hospitalizations

– Cumulative rates of survival without hospitalization similar to non-black patients

Yancy CW. N Engl J Med 2001; 344:1358-1365


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Beta Blockers

• Overall benefit in targeting the SNS in African Americans• Carvedilol:

– Decreased combined endpoint of mortality plus all cause hospitalizations

– Cumulative rates of survival without hospitalization similar to non-black patients

Yancy CW. N Engl J Med 2001; 344:1358-1365


Beta blockers should be initiated

in all African Americans with

HFrEF unless contraindicated

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ACE Inhibitors and ARBs

• SOLVD Treatment: the only major

trial to report out subgroup data

in black patients

• Enalapril group:

• 7.9 more hospitalizations per

100-patient years (95% CI 5.3 –

10.6) in African American

patients vs white patients

Exner DV, et al. N Engl J Med. 2001;344(18):1351-7.

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• MS is diagnosed with HFrEF and treated with IV diuretics

• After 48 hours of IV diuresis, MS is ready to transition to oral diuretics and

begin medication optimization.

• 12/5/2019



• In addition to stopping hydrochlorothiazide, what medication changes do you

want to make before discharge?• A: Start metoprolol tartrate and lisinopril

• B: Start metoprolol succinate and spironolactone

• C: Start carvedilol and lisinopril

• D: Start carvedilol and hydralazine/isosorbide dinitrate

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• MS presents to clinic 3 months after discharge for routine follow-up. She reports

shortness of breath when walking up more than 1 flight of stairs. She reports no

symptoms consistent with volume overload and appears euvolemic on exam.

• Current medications: carvedilol 25 mg BID, lisinopril 10 mg daily, metformin 1000 mg BID,

atorvastatin 40 mg daily, torsemide 20 mg daily

• Vitals: HR 78, BP 118/88, RR 16


• What medication change(s) should you make in clinic today?• A: Increase lisinopril to 20 mg daily

• B: Add hydralazine 25 mg/isosorbide dinitrate 10 mg TID

• C: Add spironolactone 25 mg daily

• D: Stop lisinopril and start sacubitril/valsartan 24/26 mg BID after 36 hour washout

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Hydralazine/Isosorbide dinitrate (HI): VHeFT I

• Evaluate the addition of vasodilator therapy in 642 HFrEF patients• Intervention: Prazosin 20 mg/day (N=183) vs. HI 300/160 mg/day (N=186) vs. placebo (N=273)

Carson P. J Card Fail. 1999;5(3):178-87.

Cohn JN. NEJM. 1986. 314(24):1547-52.

Endpoint Prazosin HI Placebo RR P-value NNT

Overall Mortality 49.7% 38.7% 44.0% NA 0.093 --

Mortality at 2 years -- 25.6% 34.3% 0.75 <0.028 12

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Hydralazine/Isosorbide dinitrate (HI): VHeFT I

• Evaluate the addition of vasodilator therapy in 642 HFrEF patients• Intervention: Prazosin 20 mg/day (N=183) vs. HI 300/160 mg/day (N=186) vs. placebo (N=273)

African American Subgroup White Subgroup

HI vs. PL P<0.041 HI vs. PL P<0.48


Cohn JN. NEJM. 1986. 314(24):1547-52.

Endpoint Prazosin HI Placebo RR P-value NNT

Overall Mortality 49.7% 38.7% 44.0% NA 0.093 --

Mortality at 2 years -- 25.6% 34.3% 0.75 <0.028 12

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Hydralazine/Isosorbide dinitrate (HI): VHeFT II

• Enalapril 20 mg/day vs. HI 300/160 mg/day• Mortality at 2 years: Enalapril 18% vs. HI 25% (P=0.016, NNT 15)


Cohn JN. NEJM. 1991. 325(5):303-310.

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Hydralazine/Isosorbide dinitrate (HI): VHeFT II

• Enalapril 20 mg/day vs. HI 300/160 mg/day• Mortality at 2 years: Enalapril 18% vs. HI 25% (P=0.016, NNT 15)

• White patients responded better to enalapril than HI

• African American patients responded to both therapies

African American Subgroup White Subgroup

E vs. HI P<0.95 E vs. HI P<0.02


Cohn JN. NEJM. 1991. 325(5):303-310.

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Hydralazine/Isosorbide dinitrate (HI): AHeFT

• Evaluate the efficacy of HI in black patients with NYHA

class III or IV heart failureObjective

• Randomized, double-blind, placebo-controlled

• HI 225 mg/120 mg/day vs. placebo in addition to standard

HFrEF therapiesMethods

• Weighted composite score of death, 1st heart failure

hospitalization and change in quality of life (QoL)Primary Outcome

Taylor AL. NEJM. 2004. 351(20):2049-2057.

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AHeFT: Baseline Characteristics

CharacteristicHI

(N=518)

Placebo

(N=532)

Age (yr) 56.7 56.9

Male (%) 55.8 63.9

Heart Failure Etiology (%)

• Ischemic

• HTN

• Other

23.4

40.0

36.7

22.7

37.4

39.8

NYHA (%)

• I

• II

• III

• IV

0.0

0.2

96.7

3.1

0.0

0.0

94.7

5.3

Ejection Fraction (%) 23.9 24.2

Diabetes (%)* 44.8 37.0

Systolic Blood Pressure (mmHg) 127.2 125.3

Medications (%)

• Diuretic

• Ace Inhibitor/ARB

• Beta Blocker

• Digoxin

• Spironolactone

88.0

86.6

74.1

58.5

40.2

91.5

86.0

73.5

60.7

37.6

*P=0.01

Taylor AL. NEJM. 2004. 351(20):2049-2057.

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AHeFT: Outcomes

Outcome HI Placebo P-value NNT

Primary composite score -0.1±1.9 -0.5±2.0 0.01 NA

Death from any cause 6.2% 10.2% 0.02 25

1st hospitalization for heart failure 16.4% 24.4% 0.001 13

Change in quality of life score at 6 months -5.6±20.6 -2.7±21.2 0.02 NA

Scoring System for Composite Endpoint

Death -3

Survival to end of trial 0

1st hospitalization for heart failure -1

No hospitalization 0

Change in QoL

• Improvement by >10 units

• Improvement by 5-9 units

• Change by <5 units

• Worsening by 5-9 units

• Worsening by >10 units

+2

+1

0

-1

-2

Taylor AL. NEJM. 2004. 351(20):2049-2057.

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Sacubitril/Valsartan

• PARADIGM-HF

• Primary endpoint: CV mortality and first HF hospitalization

• Low enrollment of black patients resulting in wide confidence interval

• Higher rates of angioedema (1.79% vs 0.44%)

• PIONEER

• Primary endpoint: time-averaged reduction in NT-proBNP

• Proportion of black patients more similar to population seen in clinical practice

Trial Subjects Total N % BlackWhite

(95% CI)

Black

(95% CI)

Overall

(95% CI)NNT

PARADIGM-

HF

Stable

HFrEF8399 5.1%

HR

0.81 (0.73-0.90)

HR

0.81 (0.57-1.15)

HR

0.80 (0.73-0.87)22

PIONEER ADHF 881 35.9%Ratio of change

0.68 (0.58-0.80)

Ratio of change

0.72 (0.57-0.89)

Ratio of change

0.71 (0.63-0.81)N/A

Mcmurray JJ, et al. N Engl J Med. 2014;371(11):993-1004.

Velazquez EJ et al. N Engl J Med. 2019;380(6):539-548.

POSTER PRESENTATION

Shi V, et al. Int J Cardiol. 2018;264:118-123.

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Aldosterone Receptor Antagonists

Trial ARATotal

N

%

Black

White

HR (95% CI)

Black

HR (95% CI)

Overall

HR (95% CI)NNT

RALES Spironolactone 1,663 7 0.70 (0.59-0.82) 0.87 (0.47-1.59) HR 0.70 (0.60-0.82) 10

Vardeny O, et al. Circ Heart Fail. 2013;6(5):970-6.

Pitt B, et al. N Engl J Med. 1999;341(10):709-17.

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• MS presents to clinic 3 months after discharge for routine follow-up. She reports

shortness of breath when walking up more than 1 flight of stairs. She reports no

symptoms consistent with volume overload and appears euvolemic on exam.

• Current medications: carvedilol 25 mg BID, lisinopril 10 mg daily, metformin 1000 mg BID,

atorvastatin 40 mg daily, torsemide 20 mg daily

• Vitals: HR 78, BP 118/88, RR 16


• What medication change(s) should you make in clinic today?• A: Increase lisinopril to 20 mg daily

• B: Add hydralazine 25 mg/isosorbide dinitrate 10 mg TID

• C: Add spironolactone 25 mg daily

• D: Stop lisinopril and start sacubitril/valsartan 24/26 mg BID after 36 hour washout

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Patient-Specific Decision Making Tools

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Side-by-Side Comparison

NNT over 10 months (African Americans only)

• All-cause mortality: 25

• First hospitalization for HF: 13

NNT over 27 months (overall population)

• All-cause mortality: 36

• First hospitalization for HF: 36

Hydralazine/Isosorbide Dinitrate Sacubitril/Valsartan

Pro

• Minimal blood pressure reduction

• No direct effects on renal function or electrolytes

• Anti-anginal in patients with stable angina

Con

• Minimal blood pressure reduction

• Adherence to three times daily dosing

• High incidence of headaches

• Two copayments

Pro

• Large blood pressure reduction

• Twice daily dosing

Con

• Large blood pressure reduction

• Cost

• Hyperkalemia

• Hypotension

• No data for use in hemodialysis

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• MS presents to clinic for routine follow-up and is doing well. She complains of

moderate headaches that are not resolved with acetaminophen approximately

3-4 times per week. During the interview, she mentions frequently missing her

midday dose of hydralazine/isosorbide dinitrate (HI).

• Current medications: carvedilol 25 mg BID, lisinopril 20 mg daily, hydralazine 75

mg/isosorbide dinitrate 40 mg TID, metformin 1000 mg BID, atorvastatin 40 mg daily,

torsemide 40 mg daily

• Vitals: HR 78, BP 128/89, RR 16


• What change(s) do you want to make to her medication regimen?• A: Stop HI and start sacubitril/valsartan 49/51 mg twice daily after 36 hour washout of lisinopril

• B: Decrease HI to 25 mg/10 mg TID

• C: Stop HI and start spironolactone 25 mg daily

• D: Stop HI and increase lisinopril to 40 mg daily

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Hydralazine/Isosorbide Dinitrate: Adverse Events

• AHeFT• HI discontinued because of headache: 7%

• Systolic blood pressure change: HI -1.9 mmHg vs. Placebo +0.8 mmHg

• AHeFT Extension • Adverse Events: headache: 34%, dizziness 16%, hypotension 6%

• Discontinuation due to adverse events: 6%

AHeFT Adverse Events HI Placebo P-value

Heart failure exacerbation 8.7% 12.8% 0.04

Severe heart failure exacerbation 3.1% 7.0% 0.005

Headache 47.5% 19.2% <0.001

Dizziness 29.3% 12.3% <0.001

Taylor AL. NEJM. 2004. 351(20):2049-2057.

Yancy CW. Am J Cardiol. 2007;100(4):684-9.

BiDil (isosorbide dinitrate and hydralazine hydrochloride) [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals; March 2019.

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Hydralazine/Isosorbide Dinitrate: Adverse Events

• AHeFT• HI discontinued because of headache: 7%

• Systolic blood pressure change: HI -1.9 mmHg vs. Placebo +0.8 mmHg

• AHeFT Extension • Adverse Events: headache: 34%, dizziness 16%, hypotension 6%

• Discontinuation due to adverse events: 6%

AHeFT Adverse Events HI Placebo P-value

Heart failure exacerbations 8.7% 12.8% 0.04

Severe heart failure exacerbation 3.1% 7.0% 0.005

Headache 47.5% 19.2% <0.001

Dizziness 29.3% 12.3% <0.001

Taylor AL. NEJM. 2004. 351(20):2049-2057.

Yancy CW. Am J Cardiol. 2007 Aug 15;100(4):684-9.

BiDil (isosorbide dinitrate and hydralazine hydrochloride) [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals; March 2019.

Acetaminophen can be used to treat headaches caused by HI

Headaches tend to improve with consistent dosing

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Hydralazine/Isosorbide Dinitrate: Compliance

• AHeFT• Mean number of tablets: HI 3.8±2.5 vs. placebo 4.7±2.2 (P<0.001)

• Target dose achieved in 68% of patients

• AHeFT Extension• Mean number of tablets: 3.7±1.8

• Mean dose: hydralazine 138 mg/day, isosorbide dinitrate 74 mg/day

• Compliance: 87%

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Hydralazine/Isosorbide Dinitrate: Compliance

• AHeFT• Mean number of tablets: HI 3.8±2.5 vs. placebo 4.7±2.2 (P<0.001)

• Target dose achieved in 68% of patients

• AHeFT Extension• Mean number of tablets: 3.7±1.8

• Mean dose: hydralazine 138 mg/day, isosorbide dinitrate 74 mg/day

• Compliance: 87%

• Get with the Guidelines-Heart Failure Registry• Prescribing rates at discharge

– African Americans: 22.7%

– ACE Inhibitor/ARB intolerance: 18.2%

• Prescription fill rate at 90 days

– African Americans: 46%

– ACE Inhibitor/ARB intolerance: 48%

Outcome at 3 years

(African American)

HI at

Discharge

(N=316)

No HI at

discharge

(N=1076)

P-value

All-cause mortality 53.9% 51.9% 0.39

All-cause readmission 85.7% 83.9% 0.53

Cardiovascular Readmission 68.9% 65.2% 0.33

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• MS presents to clinic for routine follow-up and is doing well. She complains of

moderate headaches that are not resolved with acetaminophen approximately

3-4 times per week. During the interview, she mentions frequently missing her

midday dose of hydralazine/isosorbide dinitrate (HI).

• Current medications: carvedilol 25 mg BID, lisinopril 20 mg daily, hydralazine 75

mg/isosorbide dinitrate 40 mg TID, metformin 1000 mg BID, atorvastatin 40 mg daily,

torsemide 40 mg daily

• Vitals: HR 78, BP 128/89, RR 16


• What change(s) do you want to make to her medication regimen?• A: Stop HI and start sacubitril/valsartan 49/51 mg twice daily after 36 hour washout of lisinopril

• B: Decrease HI to 25 mg/10 mg TID

• C: Stop HI and start spironolactone 25 mg daily

• D: Stop HI and increase lisinopril to 40 mg daily

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Objectives





• Evaluate new literature regarding novel HFrEF therapies and how to apply

these in African American patients


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• MS presented in acute decompensated heart failure four days ago and was

initiated on dobutamine 5 mcg/kg/min with IV diuresis. Her home HF

medications were all held upon admission.

• Current Medications: furosemide 80 mg IV BID, atorvastatin 40 mg daily, enoxaparin 40 mg SC

daily, sliding scale insulin ACHS


• Vitals: BP 112/76, HR 96, RR 14, oxygen saturation 98%

Pulmonary artery pressure 43/30 mm Hg

Mean pulmonary artery pressure 34 mm Hg

Central venous pressure 15 mm Hg

Cardiac index 1.8 L/min/m2

Systemic vascular resistance 2294 dynes/cm5

Mixed venous oxygen saturation 47%

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• The team plans to wean off inotropes and transition her to oral therapy over

the coming days.

• What afterload reducing agent would you use to support her dobutamine

wean?• A: Captopril

• B: Valsartan

• C: Sacubitril/valsartan

• D: Hydralazine/isosorbide dinitrate

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Afterload Reduction in ADHF

𝐶𝑎𝑟𝑑𝑖𝑎𝑐 𝑂𝑢𝑡𝑝𝑢𝑡 =𝐵𝑙𝑜𝑜𝑑 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒

𝑆𝑦𝑠𝑡𝑒𝑚𝑖𝑐 𝑉𝑎𝑠𝑐𝑢𝑙𝑎𝑟 𝑅𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒

Medication % African

American

Cardiac Index

(L/min/m2)

Systemic Vascular Resistance

(dynes/cm5)

Hydralazine/isosorbide dinitrate

and ACE inhibitor/ARB1

20% + 1.7 - 630

ACE inhibitor/ARB alone1 21% + 0.5 NS

Sacubitril/valsartan2 Not available + 0.76 - 738

1 Compared from hospital admission to follow-up2 Compared from pre and post initiation

Addition of hydralazine/isosorbide dinitrate to ACE inhibitor/ARB after ADHF event requiring invasive

hemodynamic monitoring:

• Reduction in all-cause mortality (34% vs 41%, p=0.04)

• Reduction in all-cause mortality and HF hospitalization (70% vs 85%, p=0.03)

Mullens W, et al. Am J Cardiol. 2009;103(8):1113-9.

Martyn T, et al. Poster presented at: HFSA Scientific Meeting 2019.

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Emerging Therapies in African Americans

Study Medication % African

American

Event Rate p-value for

interactionTreatment

n (%)

Control

n (%)

EMPA-REG

OUTCOME

Empagliflozin5.1 39 (16.4%) 14 (11.7%) 0.09

CANVAS Canagliflozin 3.3 18.6%a 37.0%a 0.40

DECLARE-TIMI 58 Dapagliflozin 3.5b 68 (3.9%) 70 (4.0%) 0.23

DAPA-HF Dapagliflozin 4.8 26 (21.3%) 32 (30.8%) >0.05

FAIR-HF Ferric

carboxymaltose0.002c Not available, only 1 non-white subject

enrolled

CONFIRM-HF Ferric

carboxymaltose1c Not available, only 2 non-white subjects

enrolled

IRONOUT-HF Iron

polysaccharide25 Data not presented

a Per 1000 patient years; b Non-Caucasian; c Non-white

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Objectives







• Design an individualized treatment plan for African American patients with

HFrEF

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All-Cause Mortality and Treatment Effect

Trial Medication% African

American

Follow-up Period

(months)

Overall Population

NNT

RALES Spironolactone 7 24 11

COPERNICUS Carvedilol 5 10.4 15

CIBIS-II Bisoprolol NA 16 19

US Carvedilol HF

TrialsCarvedilol 20 15.1 22

SOLVD Treatment Enalapril 9.5 41.4 23

A-HeFTHydralazine/

isosorbide dinitrate100 10 25

MERIT-HF Metoprolol succinate 5 12 27

PARADIGM-HF Sacubitril/valsartan 5.1 27 36

DAPA-HF Dapagliflozin 4.7 18.2 44

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HFrEF Treatment Plan in African Americans

Treatment of Stage C/D HFrEF

in African Americans

Beta blockers +

ACE inhibitors/ARBs

Add hydralazine/

isosorbide dinitrate

Change ACE inhibitor/ARB

to sacubitril-valsartanAdd spironolactoneAdd SGLT2 inhibitor

Type 2 Diabetes

SBP > 100 mm Hg

eGFR > 30 mL/min/1.73 m2

K < 5.2 mEq/L

CrCl > 30 mL/min

K < 5 mEq/L

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Summary

• African Americans with HFrEF are considered a “high-risk” population with a

larger burden of disease and more severe disease than the general population

• African American patients are severely underrepresented in clinical trials, making

application of guideline-directed therapies difficult

• Hydralazine/isosorbide dinitrate has the most robust evidence for benefit in the

African American population

• Use is limited by high incidence of headaches and adherence to three times daily dosing

• Use of emerging HFrEF therapies in African Americans is reasonable, but

continues to be limited by low enrollment

• Future research should focus on including a larger representation of African

Americans in landmark trials

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Heart Failure Treatment in African

American Patients

Theresa Kline, PharmD & Lauren Kemp, PharmD

University of North Carolina Medical Center

Residency Program Director: Ian B. Hollis, PharmD, BCPS-AQ Cardiology

December 5, 2019

heart failure treatment in african american patients

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