Guideline-Directed Medical Therapy (GDMT): Building the ...
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Guideline-Directed Medical Therapy (GDMT): Building the Backbone Before Discharge Laila Najia, PharmD [email protected] @laila_najia Andrew Willeford, PharmD, PhD [email protected] @AndrewWillefor3 PGY2 Cardiology Pharmacy Residents University of Maryland School of Pharmacy ACCP Case Conference February 9 th , 2021
Transcript of Guideline-Directed Medical Therapy (GDMT): Building the ...
Defining the Activity and Role of CaMKIIδ During β-adrenergic
StimulationLaila Najia, PharmD [email protected]
@AndrewWillefor3
ACCP Case Conference
February 9th, 2021
Disclosures
• We have no actual or potential conflicts of interest in relation to this presentation
Objectives
1. Describe efficacy and safety considerations for inpatient initiation of GDMT
2. Explain the role of shared decision-making in heart failure polypharmacy
3. Given a hospitalized patient with newly diagnosed heart failure, design an appropriate GDMT
regimen that balances efficacy and safety with financial considerations
Considerations in building the backbone
Shared decision-making
Shared decision-making
The backbone
Patient Case
• AL is a 58 white male presenting with progressive 12 lb weight gain, increasing SOB for past 3 weeks, and confusion.
• PMH: HTN, HLD
• Social History – Denies alcohol use – Denies tobacco and illicit substance use
• Physical Exam Findings – AOx2 – Extremities cool to touch – 2+ pitting edema bilaterally up to mid-calf – Positive for crackles in mid-lung fields – Positive JVD 15 cm
AO: alert and oriented; SOB: Shortness of breath; JVD: jugular venous distention
Patient Case Continued
Vital Signs
Pertinent TTE Findings – LV: systolic function is moderately decreased with global hypokinesis of walls – RV: no dilation with normal systolic function – EF: 30-35%
BNP: B-type natriuretic peptide; BP: blood pressure; HR: heart rate; RR: respiratory rate; RA: room air
1.83.6 22
99 98
250
BP: 106/78 mmHg HR: 110 bpm RR: 14 SpO2: 92% RA
AST/ALT: 230/251 Lactate: 3 BNP: 6,800 Troponin: <0.02
Weight: 98 kg Height: 170 cm
Patient Case Continued
ISDN: isosorbide dinitrate
Day 0: Admitted to CCU
Relevant inpatient medications • Dobutamine 5 mcg/kg/min • Furosemide 120 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Hospital Clinical Course
Patient Case Continued
ISDN: isosorbide dinitrate
Relevant inpatient medications • Dobutamine 2.5 mcg/kg/min • Furosemide 120 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Day 2: Dobutamine weaned 2.5 mcg/kg/min
Hospital Clinical Course
Patient Case Continued
Day 0: Admitted to CCU
Relevant inpatient medications • Furosemide 80 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Day 2: Dobutamine weaned 2.5 mcg/kg/min
Day 4: Dobutamine D/c’d furosemide dose
decreased
Inpatient Medications
ISDN: isosorbide dinitrate
Pertinent Labs/Vitals BP: 128/78 mmHg HR: 84 bpm SCr: 0.8 mg/dL K+: 3.9 mEq/L
Considerations in building the backbone
Shared decision-making
SafetyEarly benefits
Adapted from Am J Cardiol. 2008;101:1016-1022.
10.4%
22.0%
42.3%
Atherosclerosis Risk in Communities (ARIC) Mortality Rates After Heart Failure Hospitalization
The backbone of guideline-directed medical therapy
ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor/neprilysin inhibitor; MRA: mineralocorticoid receptor antagonist; SGLT2i: sodium glucose co-transporter 2 inhibitor
ACEi/ ARB/ ARNI
CHAMP-HF Registry 2015-2017
39.1%
86.1%
32.9%
65.9%
59.9%
12.8%
66.8%
33.1%
% f
Without Contraindication and Not Treated Treated With Contraindication
Among patient eligible for all classes of medications
• 22.1% were prescribed triple therapy
• 1.1% were prescribed triple therapy at target doses
ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor/neprilysin inhibitor; MRA: mineralocorticoid receptor antagonist
2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment
EXPERT CONSENSUS DECISION PATHWAY
Answers to 10 Pivotal issues in HFrEF
1) How to initiate, add, or switch therapies to new evidence-based guideline-directed treatments for HFrEF
ACC: American College of cardiology; HFrEF: Heart failure with reduced ejection fraction
Considerations in building the backbone
Shared decision-making
SafetyPatient case
Placebo
20
15
10
5
0
P ro
b ab
ili ty
o f
Su rv
iv al
0 3 6 9 12 15 18 21 24 27 30 33 36
RALES (1999)
Days since Randomization
HR 0.80 (95% CI 0.71-0.89) P<0.001
0.6
0.5
0.4
0.3
0.2
0.1
0.0
1.0
0 0 3 6 9 12 15 18 21 24
Months since Randomization
Placebo
Dapagliflozin
Lancet. 1999;353:2001-07 N Engl J Med. 1999;341:709-17
N Engl J Med. 2014;371:993-1004
Spironolactone
(n=632)
Group 3:
• Primary outcome – compare mortality and HF readmissions at 60
and 90-days post discharge
J Am Coll Cardiol. 2008; 52:190-9. HR: heart failure; BB: beta blocker
OPTIMIZE-HF Registry: Results
BB new start on admission vs BB not prescribed
Lower mortality/rehospitalization at 60-90d HR 0.61, CI 0.44-0.83, P = 0.002
BB: Beta Blocker
PIONEER-HF
LVEF ≤40%
ARNI: 24/26 mg PO BID Vs Enalapril: 2.5-5 mg PO BID
Administered inpatient 8-week follow up
Circulation. 2019;139(19):2285-2288. LVEF: left ventricular ejection fraction; ARNI: angiotensin receptor/neprilysin inhibitor
PIONEER-HF Secondary Analysis: Trial Overview
PIONEER-HF
LVEF ≤40%
ARNI: 24/26 mg PO BID Vs Enalapril: 2.5-5 mg PO BID
Administered inpatient 8-week follow up
PIONEER-HF Secondary Analysis
after washout Administered outpatient
PIONEER-HF Secondary Analysis: Results
25
20
15
10
5
0
Baseline 1 2 3 4 5 6 7 8 9 10 11 12
Enalapril (N=441)
Sacubitril/Valsartan (N=440)
Weeks from Randomization
SOLOIST-WHF: Trial Overview
CV: cardiovascular; eGFR: estimated glomerular filtration rate; HF: heart failure; T2DM: type 2 diabetes mellitus
Inclusion Criteria
• T2DM
Intervention
• Initiated before or within 3 days of hospital discharge
Primary endpoint
• Death from CV causes, HF hospitalization, and urgent visits for HF
SOLOIST-WHF: Results
Adapted from Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183.supplemental.
• Composite endpoint: deaths from CV causes and hospitalizations and urgent visits for HF
• Benefit seen within weeks
• Driven by reduction in heart failure hospitalizations • HR 0.64 (95% CI 0.49-0.83); p<0.001)
Months since Randomization 0 3 6 9 12 15 18
100
90
80
70
60
50
40
30
20
10
0
Placebo
Sotagliflozin
Summary
BB: beta blocker; ARNI: angiotensin receptor/neprilysin inhibitor; SGLT2i: sodium glucose co-transporter 2 inhibitor; HF: heart failure
BB
within 8 weeks
Inclusion Criteria
Primary endpoint
• Number of patients treated with any beta blocker at 60 days
IMPACT-HF results
91.2%
73.4%
36.3% 28.6%
Mean Target Dose Achieved
Inpatient initiation of Beta blocker: – Increased number of patients on BB at 60 days – Increased average target dose
P < 0.0001 P = 0.02
Hospitalization
(n=204)
Group 3:
• Patient Population – hospitalized for new or worsening HF – LVEF ≤40%
• Primary outcome – Proportion of days covered (PDC) over 90 days
Carnicelli et al. J Card Fail. 2020; 26(10):s91.
Carnicelli et al. J Card Fail. 2020; 26(10):s91.
34% 50%
% o
0 1-29 30-59 60-90
Hospitalization
Curtis, et al. Initiation of MRA Therapy Pre- and Post-
Discharge
• Examine transitional adherence and persistence of MRA therapy in Medicare beneficiaries
Inclusion Criteria
MRA: mineralocorticoid receptor antagonist
Curtis, et al. Initiation of MRA Therapy Pre- and Post-
Discharge
Filled Rx within 90 days Filled Rx within 1 year
Prescription at discharge (n=561)
No Prescription at discharge (n=1525)
P < 0.001P < 0.001
Question to Audience
Which of the following medication classes had better rates of persistence as an outpatient if initiated prior to hospital discharge?
A) Beta Blockers B) ARNI C) MRA D) All of the above
Considerations in building the backbone
Shared decision-making
!
ARNI
Careful selection of patients is required
ARNI
Randomized controlled trials can provide guidance
Examine
Examine
J Am Coll Cardiol. 2004.5;43(9):1534-1541.
Inclusion Criteria
• EF < 40%
EF: ejection fraction; HF: heart failure
IMPACT-HF key criteria for patient selection
J Am Coll Cardiol. 2004.5;43(9):1534-1541.
Inclusion Criteria
• EF < 40%
Exclusion Criteria
• Cardiogenic shock
• Symptomatic hypotension
• Sick sinus syndrome
0
2
4
6
8
10
12
14
16
18
20
1.6%
0%
PIONEER-HF key criteria for patient selection
N Engl J Med. 2019.7;380(6):539-548. EF: ejection fraction; HF: heart failure
Inclusion Criteria
• EF < 40%
Exclusion Criteria
• Increasing dose of IV diuretics
• Use of IV vasodilators for the preceding 6 hours
• Use of IV inotropes for the preceding 24 hours
PIONEER-HF key criteria for patient selection
N Engl J Med. 2019.7;380(6):539-548. EF: ejection fraction; HF: heart failure; IV: intravenous
PIONEER-HF safety outcomes
n = 440 n = 441
• Diabetes mellitus type 2
• Hospitalized for symptoms of HF and received IV loop diuretics
• Prior chronic treatment with a loop diuretic for ≥30 days
SOLOIST-WHF key criteria for patient selection
Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183. HF: heart failure
Inclusion Criteria
• Diabetes mellitus type 2
• Hospitalized for symptoms of HF and received IV loop diuretics
• Prior chronic treatment with a loop diuretic for ≥30 days
Exclusion Criteria
• Use of IV vasodilators (except nitrates) within 48 hours
• Use of IV inotropes within 48 hours
SOLOIST-WHF key criteria for patient selection
Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183. HF: heart failure; IV: intravenous
0
2
4
6
8
10
12
14
16
18
20
8.6%
Adapted from JAMA.2012;308(20):2097-2107.
Example: COMPARE-HF, a retrospective analysis for MRA effectiveness and safety
or MRA at
discharge No MRA
Monitoring and clinical knowledge are still required
Adapted from JAMA.2012;308(20):2097-2107.
Example: COMPARE-HF, a retrospective analysis for MRA effectiveness and safety
or MRA at
discharge No MRA
300 0
Readmission with any diagnosis of hyperkalemia 10
HFrEF: heart failure with reduced ejection fraction; MRA: mineralocorticoid receptor antagonist
GDMT decision tree
Stable Scr, K, SBP ≥ 100, not escalating diuretics
ARNI
ACEi/ARB
BB
MRA
SGLT2i
*eGFR ≥ 30 for dapagliflozin eGFR ≥ 20 for empagliflozin
Patient Case
• It has been 2 days since dobutamine was discontinued and the patient has remained hemodynamically stable, diuresing well on furosemide 80 mg IV BID but remains in volume overload and is on hydralazine/isosorbide dinitrate 50/20 mg TID
• Labs and vitals signs from today:
• Which of the following GDMT medications would you initiate today? (select all that apply) A) Sacubitril/valsartan 24/26 mg twice daily B) Spironolactone 25 mg daily C) Empagliflozin 10 mg daily D) Metoprolol succinate 12.5 mg daily
0.83.9 20
102 114
20134 BP: 128/78 mmHg HR: 84 bpm RR: 16 SpO2: 98% RA
IV: intravenous; BID: twice daily; TID: thrice daily; BP: blood pressure; HR: heart rate; RR: respiratory rate; SpO2: oxygen saturation; RA: room air; GDMT: guideline-directed medical therapy
Patient Case
• It has been 4 days since dobutamine has been discontinued. Patient remains on sacubitril/valsartan 24/26 mg BID and spironolactone 25 mg daily. Patient is now euvolemic and maintained on furosemide 80 mg PO daily.
• Here are today’s labs and vitals:
• What GDMT would you consider initiating today? (select all that apply) A) Metoprolol succinate 12.5 mg daily B) Empagliflozin 10 mg daily C) Ivabradine 5 mg twice daily D) Digoxin 0.125 mg daily
BID: twice daily; TID: thrice daily; PO: per oral; BP: blood pressure; HR: heart rate; RR: respiratory rate; SpO2: oxygen saturation; RA: room air; GDMT: guideline-directed medical therapy
1.04.7 20
101 114
21135 BP: 109/62 mmHg HR: 72 bpm RR: 16 SpO2: 99% RA
Shared decision-making
SafetyEarly benefitsPatient case
JACC.2013;61(13):1440-1446.
Oncologist.2013:18(4):381-390.
demonstrated in pharmacoeconomic
A disparity in the perception of cost exists
System perspective Patient perspective
demonstrated in pharmacoeconomic
with cost
Coping with co-pays and care expenses
Oncologist.2013:18(4):381-390.
Oncologist.2013:18(4):381-390.
and clothing
credit
Oncologist.2013:18(4):381-390.
and clothing
credit
24%, filled only part of the
prescription
A lt
er ed
li fe
st yl
e A
lt er
ed m
ed u
ARNI
Patients with HF very likely experience similar burden
ARNI
ARNI
The disparity necessitates shared decision-making
Clinician Patient
Clinician Patient
The disparity necessitates shared decision-making
Clinician Patient
INTEGRATE medical recommendations
Admit medication reconciliation
Admit medication reconciliation
GDMT: guideline-directed medical therapy
Admit medication reconciliation
Discharge education and medication reconciliation
GDMT: guideline-directed medical therapy
Admit medication reconciliation
Discharge education and medication reconciliation
GDMT: guideline-directed medical therapy
Incorporate shared decision-making
Patient case wrap-up
• The patient was started on metoprolol succinate 12.5 mg daily. He was discharged from the hospital before starting an SGLT2i
• Relevant medications: – Sacubitril/valsartan 24/26 mg BID – Metoprolol succinate 12.5 mg daily – Spironolactone 25 mg daily
• Clinical HF pharmacist discussed starting empagliflozin with the patient. Copay was found to be $160/month which patient could not afford
Patient case wrap-up
• The pharmacist and patient explored the manufacturer coupon – Pay as low as $10/month up to a maximum savings of $175 per 30-day prescription – Program expires December 31, 2021
Pharmacist Patient
Adapted from Lancet.2020;396(10244):121-128.
8555 0
100
ARNI: angiotensin receptor/neprilysin inhibitor; BB: beta blocker; MRA: mineralocorticoid receptor antagonist; SGLT2i: sodium glucose co-transporter 2 inhibitor; CI: confidence interval
Acknowledgements
Guideline-Directed Medical Therapy (GDMT): Building the Backbone Before Discharge
Laila Najia, PharmD [email protected]
@AndrewWillefor3
ACCP Case Conference
February 9th, 2021
@AndrewWillefor3
ACCP Case Conference
February 9th, 2021
Disclosures
• We have no actual or potential conflicts of interest in relation to this presentation
Objectives
1. Describe efficacy and safety considerations for inpatient initiation of GDMT
2. Explain the role of shared decision-making in heart failure polypharmacy
3. Given a hospitalized patient with newly diagnosed heart failure, design an appropriate GDMT
regimen that balances efficacy and safety with financial considerations
Considerations in building the backbone
Shared decision-making
Shared decision-making
The backbone
Patient Case
• AL is a 58 white male presenting with progressive 12 lb weight gain, increasing SOB for past 3 weeks, and confusion.
• PMH: HTN, HLD
• Social History – Denies alcohol use – Denies tobacco and illicit substance use
• Physical Exam Findings – AOx2 – Extremities cool to touch – 2+ pitting edema bilaterally up to mid-calf – Positive for crackles in mid-lung fields – Positive JVD 15 cm
AO: alert and oriented; SOB: Shortness of breath; JVD: jugular venous distention
Patient Case Continued
Vital Signs
Pertinent TTE Findings – LV: systolic function is moderately decreased with global hypokinesis of walls – RV: no dilation with normal systolic function – EF: 30-35%
BNP: B-type natriuretic peptide; BP: blood pressure; HR: heart rate; RR: respiratory rate; RA: room air
1.83.6 22
99 98
250
BP: 106/78 mmHg HR: 110 bpm RR: 14 SpO2: 92% RA
AST/ALT: 230/251 Lactate: 3 BNP: 6,800 Troponin: <0.02
Weight: 98 kg Height: 170 cm
Patient Case Continued
ISDN: isosorbide dinitrate
Day 0: Admitted to CCU
Relevant inpatient medications • Dobutamine 5 mcg/kg/min • Furosemide 120 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Hospital Clinical Course
Patient Case Continued
ISDN: isosorbide dinitrate
Relevant inpatient medications • Dobutamine 2.5 mcg/kg/min • Furosemide 120 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Day 2: Dobutamine weaned 2.5 mcg/kg/min
Hospital Clinical Course
Patient Case Continued
Day 0: Admitted to CCU
Relevant inpatient medications • Furosemide 80 mg IV BID • Hydralazine/ISDN 50/20 mg PO TID
Day 2: Dobutamine weaned 2.5 mcg/kg/min
Day 4: Dobutamine D/c’d furosemide dose
decreased
Inpatient Medications
ISDN: isosorbide dinitrate
Pertinent Labs/Vitals BP: 128/78 mmHg HR: 84 bpm SCr: 0.8 mg/dL K+: 3.9 mEq/L
Considerations in building the backbone
Shared decision-making
SafetyEarly benefits
Adapted from Am J Cardiol. 2008;101:1016-1022.
10.4%
22.0%
42.3%
Atherosclerosis Risk in Communities (ARIC) Mortality Rates After Heart Failure Hospitalization
The backbone of guideline-directed medical therapy
ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor/neprilysin inhibitor; MRA: mineralocorticoid receptor antagonist; SGLT2i: sodium glucose co-transporter 2 inhibitor
ACEi/ ARB/ ARNI
CHAMP-HF Registry 2015-2017
39.1%
86.1%
32.9%
65.9%
59.9%
12.8%
66.8%
33.1%
% f
Without Contraindication and Not Treated Treated With Contraindication
Among patient eligible for all classes of medications
• 22.1% were prescribed triple therapy
• 1.1% were prescribed triple therapy at target doses
ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor/neprilysin inhibitor; MRA: mineralocorticoid receptor antagonist
2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment
EXPERT CONSENSUS DECISION PATHWAY
Answers to 10 Pivotal issues in HFrEF
1) How to initiate, add, or switch therapies to new evidence-based guideline-directed treatments for HFrEF
ACC: American College of cardiology; HFrEF: Heart failure with reduced ejection fraction
Considerations in building the backbone
Shared decision-making
SafetyPatient case
Placebo
20
15
10
5
0
P ro
b ab
ili ty
o f
Su rv
iv al
0 3 6 9 12 15 18 21 24 27 30 33 36
RALES (1999)
Days since Randomization
HR 0.80 (95% CI 0.71-0.89) P<0.001
0.6
0.5
0.4
0.3
0.2
0.1
0.0
1.0
0 0 3 6 9 12 15 18 21 24
Months since Randomization
Placebo
Dapagliflozin
Lancet. 1999;353:2001-07 N Engl J Med. 1999;341:709-17
N Engl J Med. 2014;371:993-1004
Spironolactone
(n=632)
Group 3:
• Primary outcome – compare mortality and HF readmissions at 60
and 90-days post discharge
J Am Coll Cardiol. 2008; 52:190-9. HR: heart failure; BB: beta blocker
OPTIMIZE-HF Registry: Results
BB new start on admission vs BB not prescribed
Lower mortality/rehospitalization at 60-90d HR 0.61, CI 0.44-0.83, P = 0.002
BB: Beta Blocker
PIONEER-HF
LVEF ≤40%
ARNI: 24/26 mg PO BID Vs Enalapril: 2.5-5 mg PO BID
Administered inpatient 8-week follow up
Circulation. 2019;139(19):2285-2288. LVEF: left ventricular ejection fraction; ARNI: angiotensin receptor/neprilysin inhibitor
PIONEER-HF Secondary Analysis: Trial Overview
PIONEER-HF
LVEF ≤40%
ARNI: 24/26 mg PO BID Vs Enalapril: 2.5-5 mg PO BID
Administered inpatient 8-week follow up
PIONEER-HF Secondary Analysis
after washout Administered outpatient
PIONEER-HF Secondary Analysis: Results
25
20
15
10
5
0
Baseline 1 2 3 4 5 6 7 8 9 10 11 12
Enalapril (N=441)
Sacubitril/Valsartan (N=440)
Weeks from Randomization
SOLOIST-WHF: Trial Overview
CV: cardiovascular; eGFR: estimated glomerular filtration rate; HF: heart failure; T2DM: type 2 diabetes mellitus
Inclusion Criteria
• T2DM
Intervention
• Initiated before or within 3 days of hospital discharge
Primary endpoint
• Death from CV causes, HF hospitalization, and urgent visits for HF
SOLOIST-WHF: Results
Adapted from Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183.supplemental.
• Composite endpoint: deaths from CV causes and hospitalizations and urgent visits for HF
• Benefit seen within weeks
• Driven by reduction in heart failure hospitalizations • HR 0.64 (95% CI 0.49-0.83); p<0.001)
Months since Randomization 0 3 6 9 12 15 18
100
90
80
70
60
50
40
30
20
10
0
Placebo
Sotagliflozin
Summary
BB: beta blocker; ARNI: angiotensin receptor/neprilysin inhibitor; SGLT2i: sodium glucose co-transporter 2 inhibitor; HF: heart failure
BB
within 8 weeks
Inclusion Criteria
Primary endpoint
• Number of patients treated with any beta blocker at 60 days
IMPACT-HF results
91.2%
73.4%
36.3% 28.6%
Mean Target Dose Achieved
Inpatient initiation of Beta blocker: – Increased number of patients on BB at 60 days – Increased average target dose
P < 0.0001 P = 0.02
Hospitalization
(n=204)
Group 3:
• Patient Population – hospitalized for new or worsening HF – LVEF ≤40%
• Primary outcome – Proportion of days covered (PDC) over 90 days
Carnicelli et al. J Card Fail. 2020; 26(10):s91.
Carnicelli et al. J Card Fail. 2020; 26(10):s91.
34% 50%
% o
0 1-29 30-59 60-90
Hospitalization
Curtis, et al. Initiation of MRA Therapy Pre- and Post-
Discharge
• Examine transitional adherence and persistence of MRA therapy in Medicare beneficiaries
Inclusion Criteria
MRA: mineralocorticoid receptor antagonist
Curtis, et al. Initiation of MRA Therapy Pre- and Post-
Discharge
Filled Rx within 90 days Filled Rx within 1 year
Prescription at discharge (n=561)
No Prescription at discharge (n=1525)
P < 0.001P < 0.001
Question to Audience
Which of the following medication classes had better rates of persistence as an outpatient if initiated prior to hospital discharge?
A) Beta Blockers B) ARNI C) MRA D) All of the above
Considerations in building the backbone
Shared decision-making
!
ARNI
Careful selection of patients is required
ARNI
Randomized controlled trials can provide guidance
Examine
Examine
J Am Coll Cardiol. 2004.5;43(9):1534-1541.
Inclusion Criteria
• EF < 40%
EF: ejection fraction; HF: heart failure
IMPACT-HF key criteria for patient selection
J Am Coll Cardiol. 2004.5;43(9):1534-1541.
Inclusion Criteria
• EF < 40%
Exclusion Criteria
• Cardiogenic shock
• Symptomatic hypotension
• Sick sinus syndrome
0
2
4
6
8
10
12
14
16
18
20
1.6%
0%
PIONEER-HF key criteria for patient selection
N Engl J Med. 2019.7;380(6):539-548. EF: ejection fraction; HF: heart failure
Inclusion Criteria
• EF < 40%
Exclusion Criteria
• Increasing dose of IV diuretics
• Use of IV vasodilators for the preceding 6 hours
• Use of IV inotropes for the preceding 24 hours
PIONEER-HF key criteria for patient selection
N Engl J Med. 2019.7;380(6):539-548. EF: ejection fraction; HF: heart failure; IV: intravenous
PIONEER-HF safety outcomes
n = 440 n = 441
• Diabetes mellitus type 2
• Hospitalized for symptoms of HF and received IV loop diuretics
• Prior chronic treatment with a loop diuretic for ≥30 days
SOLOIST-WHF key criteria for patient selection
Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183. HF: heart failure
Inclusion Criteria
• Diabetes mellitus type 2
• Hospitalized for symptoms of HF and received IV loop diuretics
• Prior chronic treatment with a loop diuretic for ≥30 days
Exclusion Criteria
• Use of IV vasodilators (except nitrates) within 48 hours
• Use of IV inotropes within 48 hours
SOLOIST-WHF key criteria for patient selection
Bhatt et al. N Engl J Med. 2020.DOI:10.1056/NEJMoa2030183. HF: heart failure; IV: intravenous
0
2
4
6
8
10
12
14
16
18
20
8.6%
Adapted from JAMA.2012;308(20):2097-2107.
Example: COMPARE-HF, a retrospective analysis for MRA effectiveness and safety
or MRA at
discharge No MRA
Monitoring and clinical knowledge are still required
Adapted from JAMA.2012;308(20):2097-2107.
Example: COMPARE-HF, a retrospective analysis for MRA effectiveness and safety
or MRA at
discharge No MRA
300 0
Readmission with any diagnosis of hyperkalemia 10
HFrEF: heart failure with reduced ejection fraction; MRA: mineralocorticoid receptor antagonist
GDMT decision tree
Stable Scr, K, SBP ≥ 100, not escalating diuretics
ARNI
ACEi/ARB
BB
MRA
SGLT2i
*eGFR ≥ 30 for dapagliflozin eGFR ≥ 20 for empagliflozin
Patient Case
• It has been 2 days since dobutamine was discontinued and the patient has remained hemodynamically stable, diuresing well on furosemide 80 mg IV BID but remains in volume overload and is on hydralazine/isosorbide dinitrate 50/20 mg TID
• Labs and vitals signs from today:
• Which of the following GDMT medications would you initiate today? (select all that apply) A) Sacubitril/valsartan 24/26 mg twice daily B) Spironolactone 25 mg daily C) Empagliflozin 10 mg daily D) Metoprolol succinate 12.5 mg daily
0.83.9 20
102 114
20134 BP: 128/78 mmHg HR: 84 bpm RR: 16 SpO2: 98% RA
IV: intravenous; BID: twice daily; TID: thrice daily; BP: blood pressure; HR: heart rate; RR: respiratory rate; SpO2: oxygen saturation; RA: room air; GDMT: guideline-directed medical therapy
Patient Case
• It has been 4 days since dobutamine has been discontinued. Patient remains on sacubitril/valsartan 24/26 mg BID and spironolactone 25 mg daily. Patient is now euvolemic and maintained on furosemide 80 mg PO daily.
• Here are today’s labs and vitals:
• What GDMT would you consider initiating today? (select all that apply) A) Metoprolol succinate 12.5 mg daily B) Empagliflozin 10 mg daily C) Ivabradine 5 mg twice daily D) Digoxin 0.125 mg daily
BID: twice daily; TID: thrice daily; PO: per oral; BP: blood pressure; HR: heart rate; RR: respiratory rate; SpO2: oxygen saturation; RA: room air; GDMT: guideline-directed medical therapy
1.04.7 20
101 114
21135 BP: 109/62 mmHg HR: 72 bpm RR: 16 SpO2: 99% RA
Shared decision-making
SafetyEarly benefitsPatient case
JACC.2013;61(13):1440-1446.
Oncologist.2013:18(4):381-390.
demonstrated in pharmacoeconomic
A disparity in the perception of cost exists
System perspective Patient perspective
demonstrated in pharmacoeconomic
with cost
Coping with co-pays and care expenses
Oncologist.2013:18(4):381-390.
Oncologist.2013:18(4):381-390.
and clothing
credit
Oncologist.2013:18(4):381-390.
and clothing
credit
24%, filled only part of the
prescription
A lt
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st yl
e A
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ARNI
Patients with HF very likely experience similar burden
ARNI
ARNI
The disparity necessitates shared decision-making
Clinician Patient
Clinician Patient
The disparity necessitates shared decision-making
Clinician Patient
INTEGRATE medical recommendations
Admit medication reconciliation
Admit medication reconciliation
GDMT: guideline-directed medical therapy
Admit medication reconciliation
Discharge education and medication reconciliation
GDMT: guideline-directed medical therapy
Admit medication reconciliation
Discharge education and medication reconciliation
GDMT: guideline-directed medical therapy
Incorporate shared decision-making
Patient case wrap-up
• The patient was started on metoprolol succinate 12.5 mg daily. He was discharged from the hospital before starting an SGLT2i
• Relevant medications: – Sacubitril/valsartan 24/26 mg BID – Metoprolol succinate 12.5 mg daily – Spironolactone 25 mg daily
• Clinical HF pharmacist discussed starting empagliflozin with the patient. Copay was found to be $160/month which patient could not afford
Patient case wrap-up
• The pharmacist and patient explored the manufacturer coupon – Pay as low as $10/month up to a maximum savings of $175 per 30-day prescription – Program expires December 31, 2021
Pharmacist Patient
Adapted from Lancet.2020;396(10244):121-128.
8555 0
100
ARNI: angiotensin receptor/neprilysin inhibitor; BB: beta blocker; MRA: mineralocorticoid receptor antagonist; SGLT2i: sodium glucose co-transporter 2 inhibitor; CI: confidence interval
Acknowledgements
Guideline-Directed Medical Therapy (GDMT): Building the Backbone Before Discharge
Laila Najia, PharmD [email protected]
@AndrewWillefor3
ACCP Case Conference
February 9th, 2021
