Getting to Goals: Practical Approach Heart Failure Management

Presented by: Elizabeth Petrovitch, Pharm.D., BCPS

DMC Harper-Hutzel Hospital

Course Speaker Disclosure Information

Elizabeth Petrovitch, Pharm.D., BCPS

Disclosures

None

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You know the meds and the goals…but how to you get there once you start?

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Quick Review: Which medications and when?

Aldosterone Antagonist

Beta Blocker

ACEi/ARB/ ARNI

Vasodilators

Ivabradine

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First & Second: ACEi/ARB and/or Beta Blockers

• For stable patients: Either or both

• If congested: ACEi

• If dry & adequate resting heart rate: beta blocker

• Consider BP, HR, and SCr

CIBIS III Trial Data

Circulation. 2005 Oct 18;112(16):2426-35. 5

Third: Aldosterone Antagonist

• After ACEi/ARB and Beta blocker on board

• NOT necessary to achieve maximally tolerated doses of other drugs first!

N Engl J Med 2003;348:1309-21.N Engl J Med 1999:341:709-17.

EPHESUS Baseline Characteristics

RALES Baseline Characteristics

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Fourth: Additional meds PRN

• Consider these after other agents added, or if contraindication to other agents

Patient factor NYHA Class Additional agent

Persistent volume overload II-IV Diuretic

Persistently symptomatic African Americans III-IV Hydralazine + isosorbide dinitrate

Stable on ACEi/ARB II-III ARNI

Resting HR> 70 on max tolerated beta blocker II-III Ivabradine

JACC 2017;71(2):201-230 7

What about starting with ARNI de novo?

• 2016 ACC/AHA/HFSA Focused Update• Recommendations for

sacubitril/valsartan based on PARADIGM-HF only

• PIONEER-HF• Late 2018

• In hospital initiation of ARNI vs ACEi

N Engl J Med 2019;380:539-48. 8

Initiating ARNI: Pioneer HF

N Engl J Med 2019;380:539-48. 9

Audience Response: Getting to Goals

In most cases, how frequently should GDMT meds be titrated in stable patients?

a) Every week

b) Every 2-4 weeks

c) Every 4-6 weeks

d) Every 8 weeks

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KEY concept

Titration should occur even if the patient appears “stable”!

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Recommended Titration FrequenciesClass Frequency of Titration Monitoring Parameters

(with initiation and each titration)

ACEi/ARB Q2 weeks BP, SCr, K+

Beta blocker Q2 weeks HR, BP, signs of congestion

Aldosterone antagonist Q2 weeks Electrolytes (K+), SCr

Diuretics Days to weeks BP, electrolytes, SCr

Hydralazine + isosorbide dinitrate Q2 weeks BP

ARNI Q2-4 weeks BP, electrolytes, SCr

Ivabradine Q2-4 weeks HR

JACC 2017;71(2):201-230 12

GDMT Timeline to Target – Can it be done?

+ ACEi

+BB

↑ACEi

↑BB

+AA

↑ACEi

↑BB

↑AA

↑ACEi↑BBAA

ACEi

BB

AA

@ target

0 2 4 6 8Week:

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GDMT Timeline to Target – Can it be done?

+Hydr/ ISDN

↑Hydr/ ISDN

Switch ACEi/

ARB to ARNI (36hr

washout)

↑ ARNI

+ivabr;↑ARNI

↑

ivabra

All @ target!

10 12 14 16 18 20 22 24 26Week:

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What keeps us from this goal?

• Medication side effects/adverse effects

• Medication cost/coverage

• Medication adherence

• Adherence to visit follow up

• Patient health literacy/education

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Barrier: Worsening renal function

• “Don’t mind the kidneys, treat the heart”• Renal dysfunction may be a > predictor of mortality than LVEF, NYHA Class

• Prescription rates for ACEi/BB in HF inversely related to renal function

• Agents to evaluate with impaired renal function:• ACEi/ARB/ARNI, diuretics, and aldosterone antagonists

• Remember : SCr ↑ 10-15% expected w ACEi due to inhibition of post-glomerular vasoconstriction

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Barrier: Worsening renal function

• When to evaluate:• ACEi/ARB/ARNI: Monitor SCr 1-2 weeks after initiation/adjustment • Aldosterone Antagonist: Monitor 2-3 days, then 7 days

• When to be concerned:• >30% decrease in eGFR or hyperkalemia

• Approach to management:• Dose reduction• Evaluate diuretic dose if hypovolemic• Lastly, turn to alternatives if possible

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• Identify “allergy” clearly

• Change to ARB when possible (i.e. ACEi cough)

• What about angioedema from ACEi?• Incidence:

• ACE-I: 0.1 – 1%• ARB: Unknown, but considered to be significantly lower than ACE-I

Barrier: ACEi Allergy

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Barrier: ACEi Allergy

• Risk Factors:• Female

• African American

• Previous history

• Previous drug rash

• Smoking

• Age > 65

• ACE-I induced cough

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Barrier: ACEi AllergyTrial Background Results Conclusion

Haymore BR et al

Meta-Analysis- 1 RCT- 2 retrospective cohorts- 71 patients totla

Angioedema while taking an ACE-I switched to an ARB

Risk of Angioedema: 9.4% (95% CI: 1.6-17%)

Confirmed Cases: 3.5% (95% CI: 0-9.2%)

2016 ACC/AHA HF update recommend an ARB in patients intolerant to ACE-I due to cough or angioedema

On the basis of the CHARM-Alternative study, the meta-analysis conducted by Haymore and colleagues, and the retrospective study conducted by Malde and colleagues, cross-reactivity appears to be <10%

Based on the relatively low prevalence of cross-reactivity in the literature, and the mortality benefits of angiotensin II inhibition in HF, ARBs should be considered in patients with ACE-I-induced angioedema with close monitoring

Malde B et al

Retrospective

61 patients with a diagnosis of angioedema as a result of taking an ACE-I

8% of patients who experienced angioedema from ACE-I’s previously, developed angioedema with an ARB

CHARM-Alternative

Angioedema Subgroup

83 patients w prior ACE-I-induced angioedema or anaphylaxis - 39 patients received candesartan

38 Months of Follow-up:

Angioedema recurred in 3/39 patients (7.7%)

Only 1/39 (2.6%) patients required discontinuation of candesartan

Ann Allergy Asthma Immunol. 2008;101(5):495-9. Ann Allergy Asthma Immunol. 2007;98(1):57-63.Lancet. 2003;362(9386):772-776 20

Barrier: ACEi Allergy

• If ARB is NOT acceptable due to risk/tolerance• Consider hydralazine/nitrate

Trial Interventions Patients NYHA/EF Baseline Meds

Primary outcome

Results

V-HeFT I

RandomizedDouble-blindPlacebo-controlled

ISDN/hydralazine 300/160 mg daily

Prazosin 20 mg daily

Placebo

186

183

273

II-IV

<45% (~30%)

Diuretic

Digoxin

Mortality over entire follow-up

Mortality by two years

Lower in ISDN/hydralazine group compared to placebo (difference was borderline significant (P~0.05)

Risk reduction among pts treated with ISDN/hydralazine was 34% (P<0.028)

V-HeFT II

RandomizedDouble-blind

ISDN/hydralazine 300/160 mg daily

Enalapril 20 mg daily

401

403

I-IV

(II, III=~95%)

<45% (~30%)

Diuretic

Digoxin

Mortality by two years

Hospitalization

Morality was significantly lower in the enalapril group than in the ISDN/hydralazine group (18% vs. 25%; P=0.016)

No significant difference between the two groups

N Engl J Med. 1986;314(24):1547-52.N Engl J Med. 1991;325(5): 303-10. 21

Barrier: Hyperkalemia

• Evaluate underlying reason• Meds

• ACEi/ARB/ARNI

• Aldosterone antagonist

• Changes to diuretic therapy

• Electrolyte replacement

• OTC and supplement use

• Worsening renal function

• Treatment approach• Dose reduction

• Medication withdrawal

• Potassium binding resins

JACC 2017;71(2):201-230 22

Barrier: Hyperkalemia

PEARL-HF

HARMONIZE-HF

European Heart Journal (2011) 32, 820–828.European Journal of Heart Failure (2015) 17, 1050–1056. 23

Barrier: Symptomatic Hypotension

• Evaluate underlying reason• Other vasoactive meds• Overdiuresis• Autonomic dysfunction• Medication timing

• Treatment approach• Correct above issues if possible• Use best tolerated doses• Consider ACEi/ARB over ARNI• Remember AA targets used in HF are typically below that which may

impact BP

JACC 2017;71(2):201-230 24

Barrier: Cost/Coverage

• Sacubitril/valsartan, ivabradine, patiromer• Prior Authorization often needed• Copay/cost is higher• First line agents are less costly

• Prior Authorization paperwork• Include HF phenotype and NYHA functional class• Use evidence or guideline statements to support request• Address prior therapies• Address contraindications, adverse effects• Document when appropriate that delay or interruption may cause

harm

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Barrier: Cost/Coverage

• Manufacturer vouchers• Trial cards – limited time frame and CMS restrictions

• Co-pay cards – CMS restrictions• May need reissued annually

• Samples• Ok for short term or bridging gap while awaiting PA approval

• Not noted in pharmacy systems, could lead to • DDI

• Duplication of therapy

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Barrier: Adherence

• Patient education!• Motivational interviewing

• Simplify medication regimens• Combination products

• Once daily formulations

• Consider cost

• Use tools• Pill boxes

• Medication alarms

• Smart phone applications

• Anticipate problems• When to call for refills/problems

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Barrier: Can’t reach target

• May need to use less than target doses in some patients• Frail

• Elderly

• Medication intolerance

• Focus on having ACEi/ARB/ARNI and BB first and foremost

• Goal: • Beta blocker to target, reduce other agent doses if needed

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Other Considerations: Digoxin

• Digoxin is often considered when hypotensive and other medications are contraindicated

• What does the data say?• PROVED and RADIANCE (1993): Taking away digoxin worsens HF• DIG Trial (1997): ↓ HF hospitalizations• Freeman, et al (2013): ↑death, ↔ hospitalization• Madelaire, et al (2016): ↑death, ↑ hospitalization

• Don’t add….but harmful to withdrawal?

JACC. 1993;22(4):955-62 NEJM. 1993;329(1):1-7 NEJM. 1997;336(8):525-533

Circ Cardiovasc Qual Outcomes. 2013;6:525-533 International Journal of Cardiology. 2016;221:944–950 29

Audience Response

What is the barrier to reaching goal doses you most often encounter?

a) Medication side effects/adverse effects

b) Patient adherence to medication regimen

c) Medication access/cost

d) Patient follow up

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Who will do this titration?

• Team based approach • Heart Failure Specialists

• Nursing

• Pharmacists

• Key elements• Coordination of care

• Monitoring

• Patient education

• “Brown Bag” Clinics –pharmacist managed

JACC 2017;71(2):201-230Curr Probl Cardiol 2019;00:114 31

Conclusions

• Focus on GDMT targets – if the patient can tolerate, titrate!

• Titrate even when HF is stable

• Multiple barriers exsist to reaching target, but some can be overcome

• A team approach involving medication therapy education, titration, and monitoring is key

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