Congestive heart failure chronic pharmacotherapy: Difference between revisions

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==Overview==
==Overview==
[[Pharmacotherapy]] is the mainstay of therapy for [[HFrEF]] and should be initiated before considering [[device therapy]].Three major goals of therapy for [[patients]] with [[HFrEF]] including reduction in [[mortality]], prevention of hospitalization due to worsening [[HF]], and improvement in clinical status. Suppression of [[renin-angiotensin-aldosterone]] ([[RAAS]]) and [[sympathetic nervous systems]] with [[angiotensin-converting enzyme inhibitors]] ([[ACE-I]]) or an [[angiotensin receptor-neprilysin inhibitor]] ([[ARNI]]), [[beta-blockers]], and [[mineralocorticoid receptor antagonists]] ([[MRA]]) have been shown to improve survival, reducing the risk of [[HF]] [[hospitalizations]], and reducing symptoms in [[patients]] with [[HFrEF]]. [[ACE-I]]/[[ARNI]], a [[beta-blocker]], and an [[MRA]] are recommended as cornerstone therapies for these [[patients]], unless
[[Pharmacotherapy]] is the mainstay of therapy for [[heart failure with reduced ejection fraction]] ([[HFrEF]]) and should be initiated before considering [[device therapy]].Three major goals of therapy for [[patients]] with [[HFrEF]] including reduction in [[mortality]], prevention of hospitalization due to worsening [[HF]], and improvement in clinical status. Suppression of [[renin-angiotensin-aldosterone]] ([[RAAS]]) and [[sympathetic nervous systems]] with [[angiotensin-converting enzyme inhibitors]] ([[ACE-I]]) or an [[angiotensin receptor-neprilysin inhibitor]] ([[ARNI]]), [[beta-blockers]], and [[mineralocorticoid receptor antagonists]] ([[MRA]]) have been shown to improve survival, reducing the risk of [[HF]] [[hospitalizations]], and reducing symptoms in [[patients]] with [[HFrEF]]. [[ACE-I]]/[[ARNI]], a [[beta-blocker]], and an [[MRA]] are recommended as cornerstone therapies for these [[patients]], unless
the drugs are not tolerated or contraindicated. 2021 ESC Guideline recommends the use of [[ARNI]] as a replacement for [[ACE-I]] in symptomatic [[patients]] with [[ACE-I]], [[beta-blocker]], and [[MRA]] therapies, however, an [[ARNI]] may be considered as a first-line therapy instead of an [[ACE-I]]. [[Angiotensin-receptor blockers]] ([[ARBs]]) are recommended in [[patients]] intolerant to [[ACEI]] or [[ARNI]]. The [[sodium-glucose co-transporter 2]] ([[SGLT2]]) inhibitors including [[dapagliflozin]] and [[empagliflozin]] added to therapy with [[ACE-I]]/[[ARNI]]/[[beta-blocker]]/[[MRA]] to reduce the risk of [[cardiovascular]] death and worsening [[HF]] in [[patients]] with [[HFrEF]].
the drugs are not tolerated or contraindicated. 2021 ESC Guideline recommends the use of [[ARNI]] as a replacement for [[ACE-I]] in symptomatic [[patients]] with [[ACE-I]], [[beta-blocker]], and [[MRA]] therapies. [[ARNI]] may be considered as a first-line therapy instead of an [[ACE-I]]. [[Angiotensin-receptor blockers]] ([[ARBs]]) are recommended in [[patients]] intolerant to [[ACEI]] or [[ARNI]]. The [[sodium-glucose co-transporter 2]] ([[SGLT2]]) inhibitors including [[dapagliflozin]] and [[empagliflozin]] added to therapy with [[ACE-I]]/ [[ARNI]]/ [[beta-blocker]]/ [[MRA]] to reduce the risk of [[cardiovascular]] death and worsening [[HF]] in [[patients]] with [[HFrEF]].
 
==Starting and target doses of [[medications]] and novel therapies for [[heart failure]]==
==Starting and target doses of [[medications]] and novel therapies for [[heart failure]]==
{| style="border: 2px solid #4479BA; align="left"
{| style="border: 2px solid #4479BA; align="left"
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|-
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ARNIs}}
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ARNIs}}
! style="width: 300px; background: #4479BA;" | {{fontcolor|#FFF|Starting dose}}
 
! style="width: 400px; background: #4479BA;" | {{fontcolor|#FFF|Target dose}}
|-
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Sacubitril/valsartan]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Sacubitril/valsartan]]
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|-
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ACEI}}
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ACEI}}
! style="width: 300px; background: #4479BA;" | {{fontcolor|#FFF|Starting dose}}
 
! style="width: 400px; background: #4479BA;" | {{fontcolor|#FFF|Target dose}}
|-
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Captopril]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Captopril]]
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|-
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ARBs}}
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| ARBs}}
! style="width: 300px; background: #4479BA;" | {{fontcolor|#FFF|Starting dose}}
 
! style="width: 400px; background: #4479BA;" | {{fontcolor|#FFF|Target dose}}
|-
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Candesartan]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Candesartan]]
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| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 40 mg twice daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 40 mg twice daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 160 mg twice daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 160 mg twice daily
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF|Aldosterone antagonists }}
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Eplerenone]] 
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 25 mg daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 50 mg daily
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Spironolactone]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 12.5–25 mg daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" |  25–50 mg daily
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| SGL2 ihibitors}}
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Dapagliflozin ]] 10 mg daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 10 mg daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 10 mg daily
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Empagliflozin]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 10 mg daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 10 mg daily
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| Vasodilators}}
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Hydralazine]] 
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 25 mg 3× daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 75 mg 3× daily
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Isosorbide dinitrate]] 
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 20 mg 3× daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 40 mg 3× daily
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | Fixed-dose combination [[isosorbide dinitrate]]/[[hydralazine]] 
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 20 mg/37.5 mg (1 tab) 3× daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 2 tabs 3× daily
|-
|-
! style="width: 200px; background: #4479BA;" | {{fontcolor|#FFF| Ivabradine}}
|-
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | [[Ivabradine]]
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | 2.5–5 mg twice daily
| style="padding: 0 5px; background: #F5F5F5; text-align: left;" | Titrate to [[heart rate]] 50–60 beats/min, Maximum dose 7.5 mg twice daily
|-
|-
|}
|}
{{clear}}
{|
! colspan="2" style="background: PapayaWhip;" align="center" + |The above table adopted from 2021 AHA/ACC Guideline
|-
|}<ref name="pmid33446410">{{cite journal |vauthors=Maddox TM, Januzzi JL, Allen LA, Breathett K, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Lindenfeld J, Masoudi FA, Motiwala SR, Oliveros E, Patterson JH, Walsh MN, Wasserman A, Yancy CW, Youmans QR |title=2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee |journal=J Am Coll Cardiol |volume=77 |issue=6 |pages=772–810 |date=February 2021 |pmid=33446410 |doi=10.1016/j.jacc.2020.11.022 |url=}}</ref>


== Drugs recommended in all [[patients]] with [[heart failure]] with reduced [[ejection fraction]]==
== Drugs recommended in all [[patients]] with [[heart failure]] with reduced [[ejection fraction]]==
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===[[Angiotensin receptor-neprilysin inhibitor]]===
===[[Angiotensin receptor-neprilysin inhibitor]]===
* In the [[PARADIGM-HF]] trial, [[sacubitril/valsartan]], an [[ARNI]], was superior to [[enalapril]] in reducing hospitalizations for worsening [[HF]], [[cardiovascular]] [[mortality]], and [[all-cause mortality]] in [[patients]] with ambulatory [[HFrEF]] with [[LVEF]] <_40% (changed to <_35% during the study).<ref name="pmid25176015">{{cite journal |vauthors=McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR |title=Angiotensin-neprilysin inhibition versus enalapril in heart failure |journal=N Engl J Med |volume=371 |issue=11 |pages=993–1004 |date=September 2014 |pmid=25176015 |doi=10.1056/NEJMoa1409077 |url=}}</ref>
* In the [[PARADIGM-HF]] trial, [[sacubitril/valsartan]], an [[ARNI]], was superior to [[enalapril]] in reducing hospitalizations for worsening [[HF]], [[cardiovascular]] [[mortality]], and [[all-cause mortality]] in [[patients]] with ambulatory [[HFrEF]] with [[LVEF]] ≤ 40% (changed to <_35% during the study).<ref name="pmid25176015">{{cite journal |vauthors=McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR |title=Angiotensin-neprilysin inhibition versus enalapril in heart failure |journal=N Engl J Med |volume=371 |issue=11 |pages=993–1004 |date=September 2014 |pmid=25176015 |doi=10.1056/NEJMoa1409077 |url=}}</ref>
* [[Patients]] with elevated plasma [[NP]] concentrations, an [[eGFR]] >_30 mL/min/1.73 m2 and were able to tolerate [[enalapril]] and then [[sacubitril/valsartan]].
* [[Patients]] with elevated plasma [[NP]] concentrations, an [[eGFR]]≥ 30 mL/min/1.73 m2 and were able to tolerate [[enalapril]] and then [[sacubitril/valsartan]].
*  Use of [[sacubitril/valsartan]] was associated with  improvement in [[symptoms]] and [[quality of life]] a reduction in the incidence of [[diabetes]] requiring [[insulin]] treatment,<ref name="pmid28330649">{{cite journal |vauthors=Seferovic JP, Claggett B, Seidelmann SB, Seely EW, Packer M, Zile MR, Rouleau JL, Swedberg K, Lefkowitz M, Shi VC, Desai AS, McMurray JJV, Solomon SD |title=Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial |journal=Lancet Diabetes Endocrinol |volume=5 |issue=5 |pages=333–340 |date=May 2017 |pmid=28330649 |pmc=5534167 |doi=10.1016/S2213-8587(17)30087-6 |url=}}</ref>
*  Use of [[sacubitril/valsartan]] was associated with  improvement in [[symptoms]] and [[quality of life]] a reduction in the incidence of [[diabetes]] requiring [[insulin]] treatment,<ref name="pmid28330649">{{cite journal |vauthors=Seferovic JP, Claggett B, Seidelmann SB, Seely EW, Packer M, Zile MR, Rouleau JL, Swedberg K, Lefkowitz M, Shi VC, Desai AS, McMurray JJV, Solomon SD |title=Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial |journal=Lancet Diabetes Endocrinol |volume=5 |issue=5 |pages=333–340 |date=May 2017 |pmid=28330649 |pmc=5534167 |doi=10.1016/S2213-8587(17)30087-6 |url=}}</ref>
and a reduction in the decline in [[eGFR]] <ref name="pmid29655829">{{cite journal |vauthors=Damman K, Gori M, Claggett B, Jhund PS, Senni M, Lefkowitz MP, Prescott MF, Shi VC, Rouleau JL, Swedberg K, Zile MR, Packer M, Desai AS, Solomon SD, McMurray JJV |title=Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure |journal=JACC Heart Fail |volume=6 |issue=6 |pages=489–498 |date=June 2018 |pmid=29655829 |doi=10.1016/j.jchf.2018.02.004 |url=}}</ref>as well as a reduced rate of [[hyperkalemia]]<ref name="pmid27842179">{{cite journal |vauthors=Desai AS, Vardeny O, Claggett B, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Zile MR, Lefkowitz M, Shi V, Solomon SD |title=Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial |journal=JAMA Cardiol |volume=2 |issue=1 |pages=79–85 |date=January 2017 |pmid=27842179 |doi=10.1001/jamacardio.2016.4733 |url=}}</ref>.
and a reduction in the decline in [[eGFR]] <ref name="pmid29655829">{{cite journal |vauthors=Damman K, Gori M, Claggett B, Jhund PS, Senni M, Lefkowitz MP, Prescott MF, Shi VC, Rouleau JL, Swedberg K, Zile MR, Packer M, Desai AS, Solomon SD, McMurray JJV |title=Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure |journal=JACC Heart Fail |volume=6 |issue=6 |pages=489–498 |date=June 2018 |pmid=29655829 |doi=10.1016/j.jchf.2018.02.004 |url=}}</ref>as well as a reduced rate of [[hyperkalemia]]<ref name="pmid27842179">{{cite journal |vauthors=Desai AS, Vardeny O, Claggett B, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Zile MR, Lefkowitz M, Shi V, Solomon SD |title=Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial |journal=JAMA Cardiol |volume=2 |issue=1 |pages=79–85 |date=January 2017 |pmid=27842179 |doi=10.1001/jamacardio.2016.4733 |url=}}</ref>.
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===[[Sodium-glucose co-transporter 2 inhibitors]]===
===[[Sodium-glucose co-transporter 2 inhibitors]]===
*The result of [[DAPA-HF]] trial showed the long-term effects of [[dapagliflozin]] ([[SGLT2 inhibitor]]) compared to placebo in addition to [[optimal medical therapy]] ([[OMT]]), on [[morbidity]] and [[mortality]] in [[patients]] with [[NYHA]] class II-IV, and had an [[LVEF]] <_40%.<ref name="pmid31535829">{{cite journal |vauthors=McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM |title=Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction |journal=N Engl J Med |volume=381 |issue=21 |pages=1995–2008 |date=November 2019 |pmid=31535829 |doi=10.1056/NEJMoa1911303 |url=}}</ref>
*The result of [[DAPA-HF]] trial showed the long-term effects of [[dapagliflozin]] ([[SGLT2 inhibitor]]) compared to placebo in addition to [[optimal medical therapy]] ([[OMT]]), on [[morbidity]] and [[mortality]] in [[patients]] with [[NYHA]] class II-IV, and had an [[LVEF]]≤ 40%.<ref name="pmid31535829">{{cite journal |vauthors=McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM |title=Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction |journal=N Engl J Med |volume=381 |issue=21 |pages=1995–2008 |date=November 2019 |pmid=31535829 |doi=10.1056/NEJMoa1911303 |url=}}</ref>
* Elevated plasma [[NT]]-[[proBNP]] and an [[eGFR]] >_30 mL/min/1.73 m2 were needed to initiation of therapy.
* Elevated plasma [[NT]]-[[proBNP]] and an [[eGFR]] >_30 mL/min/1.73 m2 were needed to initiation of therapy.
* Benefits of [[dapagliflozin]] in [[heart failure]] including:
* Benefits of [[dapagliflozin]] in [[heart failure]] including:
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===[[Cardiac myosin activator]]===
===[[Cardiac myosin activator]]===
* the efficacy and safety of the [[cardiac myosin]] activator, [[omecamtiv mecarbil]], in [[HFrEF]] [[patients]], was assessed by The [[GALACTIC-HF]] study.<ref name="pmid32035892">{{cite journal |vauthors=Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Legg JC, Büchele G, Varin C, Kurtz CE, Malik FI, Honarpour N |title=Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF |journal=JACC Heart Fail |volume=8 |issue=4 |pages=329–340 |date=April 2020 |pmid=32035892 |doi=10.1016/j.jchf.2019.12.001 |url=}}</ref>
* the efficacy and safety of the [[cardiac myosin]] activator, [[omecamtiv mecarbil]], in [[HFrEF]] [[patients]], was assessed by The [[GALACTIC-HF]] study.<ref name="pmid32035892">{{cite journal |vauthors=Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, Legg JC, Büchele G, Varin C, Kurtz CE, Malik FI, Honarpour N |title=Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF |journal=JACC Heart Fail |volume=8 |issue=4 |pages=329–340 |date=April 2020 |pmid=32035892 |doi=10.1016/j.jchf.2019.12.001 |url=}}</ref>
* There was no significant reduction in CV [[mortality]].
* There was no significant reduction in [[cardiovascular]] [[mortality]].
* Currently, there is no license for use of this drug.
* Currently, there is no license for use of this drug.
* This drug may be considered in the future in addition to standard therapy for [[HFrEF]]  to reduce the risk of [[cardiovascular]] mortality and hospitalization.
* This drug may be considered in the future in addition to standard therapy for [[HFrEF]]  to reduce the risk of [[cardiovascular]] mortality and hospitalization.

Latest revision as of 11:38, 19 August 2022



Resident
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Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
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Hydralazine
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ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
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Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
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Congestive heart failure end-of-life considerations

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Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

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Risk calculators and risk factors for Congestive heart failure chronic pharmacotherapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Rim Halaby, M.D. [3]

Overview

Pharmacotherapy is the mainstay of therapy for heart failure with reduced ejection fraction (HFrEF) and should be initiated before considering device therapy.Three major goals of therapy for patients with HFrEF including reduction in mortality, prevention of hospitalization due to worsening HF, and improvement in clinical status. Suppression of renin-angiotensin-aldosterone (RAAS) and sympathetic nervous systems with angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA) have been shown to improve survival, reducing the risk of HF hospitalizations, and reducing symptoms in patients with HFrEF. ACE-I/ARNI, a beta-blocker, and an MRA are recommended as cornerstone therapies for these patients, unless the drugs are not tolerated or contraindicated. 2021 ESC Guideline recommends the use of ARNI as a replacement for ACE-I in symptomatic patients with ACE-I, beta-blocker, and MRA therapies. ARNI may be considered as a first-line therapy instead of an ACE-I. Angiotensin-receptor blockers (ARBs) are recommended in patients intolerant to ACEI or ARNI. The sodium-glucose co-transporter 2 (SGLT2) inhibitors including dapagliflozin and empagliflozin added to therapy with ACE-I/ ARNI/ beta-blocker/ MRA to reduce the risk of cardiovascular death and worsening HF in patients with HFrEF.

Starting and target doses of medications and novel therapies for heart failure

Betablockers Starting dose Target dose
Bisoprolol 1.25 mg once daily 10 mg once daily
Carvedilol 3.125 mg twice daily 25 mg twice daily for weight <85 kg and 50 mg

twice daily for weight≥ 85 kg

Metoprolol succinate 12.5–25 mg daily 200 mg daily
ARNIs
Sacubitril/valsartan 24/26 mg–49/51 mg twice daily 97/103 mg twice daily
ACEI
Captopril 6.25 mg 3× daily 50 mg 3× daily
Enalapril 2.5 mg twice daily 10–20 mg twice daily
Lisinopril 2.5–5 mg daily 20–40 mg daily
Ramipril 1.25 mg daily 10 mg daily
ARBs
Candesartan 4–8 mg daily 32 mg daily
Losartan 25–50 mg daily 150 mg daily
Valsartan 40 mg twice daily 160 mg twice daily
Aldosterone antagonists
Eplerenone 25 mg daily 50 mg daily
Spironolactone 12.5–25 mg daily 25–50 mg daily
SGL2 ihibitors
Dapagliflozin 10 mg daily 10 mg daily 10 mg daily
Empagliflozin 10 mg daily 10 mg daily
Vasodilators
Hydralazine 25 mg 3× daily 75 mg 3× daily
Isosorbide dinitrate 20 mg 3× daily 40 mg 3× daily
Fixed-dose combination isosorbide dinitrate/hydralazine 20 mg/37.5 mg (1 tab) 3× daily 2 tabs 3× daily
Ivabradine
Ivabradine 2.5–5 mg twice daily Titrate to heart rate 50–60 beats/min, Maximum dose 7.5 mg twice daily
The above table adopted from 2021 AHA/ACC Guideline

[1]

Drugs recommended in all patients with heart failure with reduced ejection fraction

Medications indicated in patients with New York Heart Association (NYHA class II–IV) heart failure with reduced ejection fraction (LVEF ≤ 40%)

Recommendations for HFrEF and NYHA class II–IV
(Class I, Level of Evidence A):

ACE-I is recommended for patients with HFrEF to reduce the risk of HF hospitalization and death
Beta-blocker is recommended for patients with stable HFrEF to reduce the risk of HF hospitalization and death
MRA (Mineralocorticoid receptor antagonist) is recommended for patients with HFrEF to reduce the risk of HF hospitalization and death
Dapagliflozin or empagliflozin are recommended for patients with HFrEF to reduce the risk of HF hospitalization and death

(Class I, Level of Evidence B):

Sacubitril/valsartan is recommended as a replacement for an ACE-I in patients with HFrEF to reduce the risk of HF hospitalization and death

The above table adopted from 2021 ESC Guideline

[2]

Angiotensin-converting enzyme inhibitors

Beta-blockers

MRA or Mineralocorticoid receptor antagonists

Angiotensin receptor-neprilysin inhibitor

and a reduction in the decline in eGFR [7]as well as a reduced rate of hyperkalemia[8].

Sodium-glucose co-transporter 2 inhibitors

  • A small reversible reduction in eGFR following initiation

Medications with reducing mortality in heart failure reduced EF

Medications with reducing hospitalization in heart failure reduced EF

Other medications in HFrEF in patients with NYHA 2-4

Recommendations for heart failure with reduced ejection fraction and NYHA 2-4
Loop diuretics (Class I, Level of Evidence C):

Loop diuretics are recommended in patients with HFrEF with signs and/or symptoms of congestion to improve HF symptoms, exercise capacity, and reduce HF hospitalizations

ARB (Class I, Level of Evidence B):

ARB is recommended in symptomatic patients to reduce the risk of HF hospitalization and cardiovascular death for whom unable to tolerate an ACE-I or ARNI (patients should also receive a beta-blocker and MRA)

If-channel inhibitor :(Class IIa, Level of Evidence B) :

Ivabradine should be considered in symptomatic patients with LVEF ≤35%, sinus rhythm on ECG and a resting heart rate≥ 70 b.p.m despite treatment with maximum tolerated beta-blocker, ACE-I/(or ARNI), and an MRA, to reduce the risk of HF hospitalization and cardiovascular death

If-channel inhibitor : (Class IIa, Level of Evidence C)

Ivabradine should be considered in symptomatic patients with LVEF≤ 35%, in sinus rhythm and a resting heart rate≥ 70 b.p.m. when can not tolerate or have contraindications for a beta-blocker, for reduction the risk of HF hospitalization and cardiovascular death. Patients should also receive an ACE-I (or ARNI) and MRA

Soluble guanylate cyclase receptor stimulator: (Class IIb, Level of Evidence B)

Vericiguat may be considered in patients in NYHA class II-IV with worsening HF despite therapy with an ACE-I (or ARNI), a beta-blocker and MRA to reduce the risk of cardiovascular death or HF hospitalization

Hydralazine, isosorbide dinitrate : (Class IIa, Level of Evidence B)

Hydralazine and isosorbide dinitrate should be considered in black patients with LVEF ≤35% or with an LVEF<45% combined with a dilated left ventricle in NYHA class III-IV despite therapy with an ACE-I (or ARNI), a beta-blocker and an MRA to reduce the risk of HF hospitalization and death.1

Hydralazine, isosorbide dinitrate (Class IIb, Level of Evidence B):

Hydralazine and isosorbide dinitrate may be considered in patients with symptomatic HFrEF who unable to tolerate any of an ACE-I, an ARB, or ARNI (or they are contraindicated) to reduce the risk of death

Digoxin: (ClassIIb, Level of Evidence B)

Digoxin may be considered in patients with symptomatic HFrEF in sinus rhythm despite treating with an ACE-I (or ARNI), a beta- blocker and an MRA, to reduce the risk of hospitalization (both all-cause and HF hospitalizations)

The above table adopted from 2021 ESC Guideline

[2]

Diuretics

Angiotensin II type I receptor blockers

If -channel inhibitor

Combination of hydralazine and isosorbide dinitrate

Digoxin

Soluble guanylate cyclase receptor stimulator

Cardiac myosin activator

Management of chronic heart failure

Serial clinical evaluation , titration of Medications

Intensification 2-4 months, (1-4 weeks cycles)

  • In the presence of volume overload, adjusting diuretic dose and reevaluation in 1-2 weeks
  • In the setting of stable euvolumic status, medications initiation, increase, switch dose and follow-up in 1-2 weeks and checking basic metabolites panel, repeating cycles until no change in clinical status and reached appropriate titration

Assessment of response to medications and cardiac remodeling

Lack of response, instability

Assessment of response to medications

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