Congestive heart failure Pharmacological treatments for patients with heart failure with reduced ejection fraction: Difference between revisions
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*Loop diuretics can reduce volume overload and reduce [[shortness of breath]] and [[edema]], and thus are recommended in patients with signs or symptoms of volume overload. | *Loop diuretics can reduce volume overload and reduce [[shortness of breath]] and [[edema]], and thus are recommended in patients with signs or symptoms of volume overload. | ||
*A rise in BUN and Cr may reflect a reduction in renal perfusion, and further diuresis should only be undertaken with careful monitoring of renal function. | *A rise in BUN and Cr may reflect a reduction in renal perfusion, and further diuresis should only be undertaken with careful monitoring of renal function. | ||
===Angiotensin II receptor blockers=== | |||
An angiotensin II receptor blocker (ARB) can be used in selected patients who are intolerable of ACE-I or ARNI due to serious side effects. | |||
[[Angiotensin II receptor antagonists]] block the activation of angiotensin II AT1 receptors. Blockade of AT1 receptors directly causes [[vasodilation]], reduces secretion of [[vasopressin]], and reduces production / secretion of [[aldosterone]]. Because angiotensin II receptor antagonists do not inhibit the breakdown of [[bradykinin]] or other [[kinin]]s, they are rarely associated with the persistent [[dry cough]] and/or [[angioedema]], side effects which limit ACE inhibitor therapy. Commonly administered agents in the management of heart failure include [[Candesartan]], [[Valsartan]], [[Telmisartan]], [[Losartan]], [[Irbesartan]], and [[Olmesartan]]. The effectiveness of switching to an [[ARB]] from and [[ACE inhibitor]] was demonstrated for [[candesartan]] in the CHARM Alternative trial <ref name="pmid13678870">{{cite journal |author=Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K |title=Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial |journal=[[Lancet]] |volume=362 |issue=9386 |pages=772–6 |year=2003 |month=September |pmid=13678870 |doi=10.1016/S0140-6736(03)14284-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(03)14284-5 |accessdate=2013-04-29}}</ref>. | |||
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In general, [[ARBs]] are as effective or slightly less effective than [[ACE inhibitors]] in the treatment of [[congestive heart failure]].<ref name="pmid11823085">{{cite journal |author=Jong P, Demers C, McKelvie RS, Liu PP |title=Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials |journal=[[Journal of the American College of Cardiology]] |volume=39 |issue=3 |pages=463–70 |year=2002 |month=February |pmid=11823085 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735109701017752 |accessdate=2013-04-29}}</ref><ref name="pmid10821361">{{cite journal |author=Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B |title=Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II |journal=[[Lancet]] |volume=355 |issue=9215 |pages=1582–7 |year=2000 |month=May |pmid=10821361 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673600022133 |accessdate=2013-04-29}}</ref> It is a class 2a recommendation to substitute an [[ARB]] as an alternative to ACE inhibitors if the patient is already taking an [[ARB]] for another indication.<ref name="pmid19324966">{{cite journal |author=Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW |title=2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation |journal=[[Circulation]] |volume=119 |issue=14 |pages=e391–479 |year=2009 |month=April |pmid=19324966 |doi=10.1161/CIRCULATIONAHA.109.192065 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=19324966 |accessdate=2013-04-29}}</ref> | |||
The efficacy of adding an [[ARB]] to an [[ACE inhibitor]] was assessed in the CHARM Added trial<ref name="pmid13678869">{{cite journal |author=McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA |title=Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial |journal=[[Lancet]] |volume=362 |issue=9386 |pages=767–71 |year=2003 |month=September |pmid=13678869 |doi=10.1016/S0140-6736(03)14283-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(03)14283-3 |accessdate=2013-04-29}}</ref>. While there was a reduction in the composite primary endpoint in the study, there was no reduction in mortality. Furthermore, the VALIANT trial demonstrated that an [[ARB]] should not be added to an [[ACE inhibitor]] in the post [[MI]] setting. | |||
These negative results for adding [[ARBs]] on top of an ACE inhibitor in the post MI setting are in contrast to the results of the [[EMPHASIS HF trial]] which demonstrated that the addition of [[eplerenone]] (an [[aldosterone antagonist]]) to [[ACE inhibition]] improved clinical outcomes including mortality among patients with class II or III [[heart failure]] with a reduced [[LVEF]].<ref name="pmid21073363">{{cite journal |author=Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B |title=Eplerenone in patients with systolic heart failure and mild symptoms |journal=[[The New England Journal of Medicine]] |volume=364 |issue=1 |pages=11–21 |year=2011 |month=January |pmid=21073363 |doi=10.1056/NEJMoa1009492 |url=http://www.nejm.org/doi/abs/10.1056/NEJMoa1009492?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov |accessdate=2013-04-29}}</ref> Thus, based upon the mortality benefit observed in the EMPHASIS HF trial, an [[aldosterone antagonist]] rather than and [[ARB]] should be added to an [[ACE inhibitor]] in patients with | |||
*NYHA class III or IV [[heart failure]] who has an [[LVEF]] < 35% | |||
*NYHA class II [[heart failure]] and an [[LVEF]] < 30% | |||
*Post-[[MI]] patient who has an [[LVEF]] <u><</u> 40% who has [[heart failure]] symptoms or [[diabetes]] | |||
"Triple therapy", the combined use of an [[ACE inhibitor]], an [[ARB]] and an [[aldosterone antagonist]] is a relative contraindication. | |||
Revision as of 13:20, 19 September 2021
| Congestive Heart Failure Microchapters |
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Pathophysiology |
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Differentiating Congestive heart failure from other Diseases |
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Diagnosis |
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Treatment |
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Medical Therapy: |
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Surgical Therapy: |
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ACC/AHA Guideline Recommendations
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Specific Groups: |
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Congestive heart failure Pharmacological treatments for patients with heart failure with reduced ejection fraction On the Web |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2]
Overview
The major goals of pharmacologic treatment for patients with HFrEF are reducing mortality, reducing the risk of repeated hospitalizations due to worsening HF, and improving clinical status, functional capacity, and quality of life. The mainstay of treatment for HFrEF is the modulation of the [[renin-angiotensin-aldosterone] system] (RAAS) and sympathetic nervous system.
Therapuetic approach
- The major goals of pharmacologic treatment for patients with HFrEF are:
- 1) Reducing mortality (either all-cause or cardiovascular)
- 2) Reducing the risk of repeated hospitalizations due to worsening HF
- 3) Improving clinical status, functional capacity, and quality of life
- The cornerstone of pharmacologic management of HFrEF is the modulation of the [[renin-angiotensin-aldosterone] system] (RAAS) and sympathetic nervous system (i.e., neurohormonal blockade).
For all patients: To reduce mortality
- Angiotensin-converting enzyme inhibitors (ACE-I) or an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers, and mineralocorticoid receptor antagonists (MRA) reduce mortality, reduce the risk of repeated HF hospitalizations, and improve symptoms in patients with HFrEF.
- Thus, a combination of an ACE-I/ARNI, a beta-blocker, and an MRA is recommended as class I therapies for all HFrEF patients unless they are contraindicated or not tolerated. These drugs should be uptitrated to the doses used in the clinical trials or to maximally tolerated doses.
- Unless contraindicated or not tolerated, the sodium-glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin and empagliflozin) are also recommended for all HFrEF patients and should be added to pharmacotherapy of HFrEF patients that are already taking an ACE-I/ARNI, a beta-blocker, and an MRA, regardless of diabetes status.
| For all patients with HFrEF (LVEF<40%) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACE-I/ARNI | BB | MRA | SGLT2i | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Captopril | Sacubitrl/valsartan | Bisoprolol
| Eplerenone
| Dapagliflozin
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
For selected patients: To reduce mortality/HF hospitalization
Diuretics
- Diuretics reduce HF symptoms and HF hospitalization and improve exercise capacity. However, their effects on mortality are remained to be elucidated.
- Loop diuretics can reduce volume overload and reduce shortness of breath and edema, and thus are recommended in patients with signs or symptoms of volume overload.
- A rise in BUN and Cr may reflect a reduction in renal perfusion, and further diuresis should only be undertaken with careful monitoring of renal function.
Angiotensin II receptor blockers
An angiotensin II receptor blocker (ARB) can be used in selected patients who are intolerable of ACE-I or ARNI due to serious side effects. Angiotensin II receptor antagonists block the activation of angiotensin II AT1 receptors. Blockade of AT1 receptors directly causes vasodilation, reduces secretion of vasopressin, and reduces production / secretion of aldosterone. Because angiotensin II receptor antagonists do not inhibit the breakdown of bradykinin or other kinins, they are rarely associated with the persistent dry cough and/or angioedema, side effects which limit ACE inhibitor therapy. Commonly administered agents in the management of heart failure include Candesartan, Valsartan, Telmisartan, Losartan, Irbesartan, and Olmesartan. The effectiveness of switching to an ARB from and ACE inhibitor was demonstrated for candesartan in the CHARM Alternative trial [1].
In general, ARBs are as effective or slightly less effective than ACE inhibitors in the treatment of congestive heart failure.[2][3] It is a class 2a recommendation to substitute an ARB as an alternative to ACE inhibitors if the patient is already taking an ARB for another indication.[4]
The efficacy of adding an ARB to an ACE inhibitor was assessed in the CHARM Added trial[5]. While there was a reduction in the composite primary endpoint in the study, there was no reduction in mortality. Furthermore, the VALIANT trial demonstrated that an ARB should not be added to an ACE inhibitor in the post MI setting.
These negative results for adding ARBs on top of an ACE inhibitor in the post MI setting are in contrast to the results of the EMPHASIS HF trial which demonstrated that the addition of eplerenone (an aldosterone antagonist) to ACE inhibition improved clinical outcomes including mortality among patients with class II or III heart failure with a reduced LVEF.[6] Thus, based upon the mortality benefit observed in the EMPHASIS HF trial, an aldosterone antagonist rather than and ARB should be added to an ACE inhibitor in patients with
- NYHA class III or IV heart failure who has an LVEF < 35%
- NYHA class II heart failure and an LVEF < 30%
- Post-MI patient who has an LVEF < 40% who has heart failure symptoms or diabetes
"Triple therapy", the combined use of an ACE inhibitor, an ARB and an aldosterone antagonist is a relative contraindication.
- ↑ Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K (2003). "Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial". Lancet. 362 (9386): 772–6. doi:10.1016/S0140-6736(03)14284-5. PMID 13678870. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help) - ↑ Jong P, Demers C, McKelvie RS, Liu PP (2002). "Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials". Journal of the American College of Cardiology. 39 (3): 463–70. PMID 11823085. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help) - ↑ Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B (2000). "Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II". Lancet. 355 (9215): 1582–7. PMID 10821361. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help) - ↑ Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW (2009). "2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation". Circulation. 119 (14): e391–479. doi:10.1161/CIRCULATIONAHA.109.192065. PMID 19324966. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help) - ↑ McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA (2003). "Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial". Lancet. 362 (9386): 767–71. doi:10.1016/S0140-6736(03)14283-3. PMID 13678869. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help) - ↑ Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B (2011). "Eplerenone in patients with systolic heart failure and mild symptoms". The New England Journal of Medicine. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. PMID 21073363. Retrieved 2013-04-29. Unknown parameter
|month=ignored (help)