Congestive heart failure Sodium-glucose co-transporter 2 inhibitors: Difference between revisions
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==Sodium-glucose co-transporter 2 inhibitors== | ==Sodium-glucose co-transporter 2 inhibitors== | ||
===Indications for Sodium-glucose co-transporter 2 inhibitors=== | ===Indications for Sodium-glucose co-transporter 2 inhibitors=== | ||
According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, all patients should be on a Sodium-glucose co-transporter 2 inhibitors if: <ref name="pmid34447992">{{cite journal| author=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M | display-authors=etal| title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. | journal=Eur Heart J | year= 2021 | volume= 42 | issue= 36 | pages= 3599-3726 | pmid=34447992 | doi=10.1093/eurheartj/ehab368 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34447992 }} </ref> | According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic [[heart failure]], all patients should be on a [[Sodium-glucose co-transporter 2 inhibitors]] if: <ref name="pmid34447992">{{cite journal| author=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M | display-authors=etal| title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. | journal=Eur Heart J | year= 2021 | volume= 42 | issue= 36 | pages= 3599-3726 | pmid=34447992 | doi=10.1093/eurheartj/ehab368 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34447992 }} </ref> | ||
1. The [[left ventricular ejection fraction]] ([[LVEF]]) is ≤ 40% | 1. The [[left ventricular ejection fraction]] ([[LVEF]]) is ≤ 40% | ||
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'''''AND''''' | '''''AND''''' | ||
2. The patient is already taking an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist. | 2. The patient is already taking an [[ACE-I]]/[[ARNI]], a [[beta-blocker]], and an [[aldosterone antagonist]]. | ||
*SGLT2 inhibitors should be administered for all patients with HFrEF regardless of diabetes status. | *[[SGLT2 inhibitors]] should be administered for all patients with [[HFrEF]] regardless of [[diabetes]] status. | ||
===Background=== | ===Background=== | ||
*In DAPA-HF trial- a phase 3, placebo-controlled trial- 4744 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive dapagliflozin (10 mg once daily) or placebo, in addition to OMT <ref name="pmid31535829">{{cite journal| author=McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA | display-authors=etal| title=Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 21 | pages= 1995-2008 | pmid=31535829 | doi=10.1056/NEJMoa1911303 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31535829 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=32066149 Review in: Ann Intern Med. 2020 Feb 18;172(4):JC16] </ref>. The primary outcome was a composite of worsening HF (hospitalization or an urgent visit resulting in i.v. therapy for HF) or cardiovascular (CV) death. Results showed that over a median of 18.2 months, dapagliflozin resulted in a 26% reduction in the primary endpoint. Similar benefits were seen in patients with and without diabetes. | *In DAPA-HF trial- a phase 3, placebo-controlled trial- 4744 patients with [[NYHA class]] II–IV, and an [[LVEF]] ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive [[dapagliflozin]] (10 mg once daily) or [[placebo]], in addition to OMT <ref name="pmid31535829">{{cite journal| author=McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA | display-authors=etal| title=Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. | journal=N Engl J Med | year= 2019 | volume= 381 | issue= 21 | pages= 1995-2008 | pmid=31535829 | doi=10.1056/NEJMoa1911303 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31535829 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=32066149 Review in: Ann Intern Med. 2020 Feb 18;172(4):JC16] </ref>. The [[primary outcome]] was a composite of [[worsening HF]] ([[hospitalization]] or an urgent visit resulting in [[i.v.]] therapy for [[HF]]) or [[cardiovascular]] (CV) death. Results showed that over a median of 18.2 months, [[dapagliflozin]] resulted in a 26% reduction in the [[primary endpoint]]. Similar benefits were seen in patients with and without [[diabetes]]. | ||
*In the EMPEROR-Reduced trial, 3730 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive empagliflozin (10 mg once daily) or placebo, in addition to OMT <ref name="pmid32865377">{{cite journal| author=Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P | display-authors=etal| title=Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 15 | pages= 1413-1424 | pmid=32865377 | doi=10.1056/NEJMoa2022190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32865377 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=33197352 Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51] </ref>. The primary outcome was a composite of CV death or hospitalization for worsening HF. Results showed that over a median of 16 months empagliflozin reduced the primary endpoint by 25%. | *In the EMPEROR-Reduced trial, 3730 patients with [[NYHA]] class II–IV, and an [[LVEF]] ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive [[empagliflozin]] (10 mg once daily) or [[placebo]], in addition to OMT <ref name="pmid32865377">{{cite journal| author=Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P | display-authors=etal| title=Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 15 | pages= 1413-1424 | pmid=32865377 | doi=10.1056/NEJMoa2022190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32865377 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=33197352 Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51] </ref>. The [[primary outcome]] was a composite of CV death or [[hospitalization]] for [[worsening HF]]. Results showed that over a median of 16 months [[empagliflozin]] reduced the [[primary endpoint]] by 25%. | ||
*Therefore, dapagliflozin or empagliflozin are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an | *Therefore, [[dapagliflozin]] or [[empagliflozin]] are recommended for patients with [[HFrEF]] regardless of the presence or absence of [[diabetes]], in addition to optimal medical therapy with an [[ACE-I]]/[[ARNI]], a [[beta-blocker]], and an [[aldosterone antagonist]] <ref name="pmid34447992">{{cite journal| author=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M | display-authors=etal| title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. | journal=Eur Heart J | year= 2021 | volume= 42 | issue= 36 | pages= 3599-3726 | pmid=34447992 | doi=10.1093/eurheartj/ehab368 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34447992 }} </ref> | ||
* [[SGLT2 inhibitors]] also have [[diuretic]]/[[natriuretic]] effects which may provide additional benefits in reducing [[volume overload]] and [[congestion]] and thus may allow a reduction in the need to [[loop diuretics]]. | |||
===Dosing=== | ===Dosing=== | ||
{| class="wikitable | {| class="wikitable | ||
!SGLT2 inhibitor <ref name="pmid34447992">{{cite journal| author=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M | display-authors=etal| title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. | journal=Eur Heart J | year= 2021 | volume= 42 | issue= 36 | pages= 3599-3726 | pmid=34447992 | doi=10.1093/eurheartj/ehab368 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34447992 }} </ref> | ![[SGLT2 inhibitor]] <ref name="pmid34447992">{{cite journal| author=McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M | display-authors=etal| title=2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. | journal=Eur Heart J | year= 2021 | volume= 42 | issue= 36 | pages= 3599-3726 | pmid=34447992 | doi=10.1093/eurheartj/ehab368 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34447992 }} </ref> | ||
!Starting dose!! Target dose | !Starting dose!! Target dose | ||
|- | |- | ||
| Dapagliflozin||align="center"|10 mg QD||align="center"|10 mg QD | | [[Dapagliflozin]]||align="center"|10 mg QD||align="center"|10 mg QD | ||
|- | |- | ||
| Empagliflozin||align="center"|10 mg QD||align="center"|10 mg QD | | [[Empagliflozin]]||align="center"|10 mg QD||align="center"|10 mg QD | ||
|} | |} | ||
===Adverse effect=== | ===Adverse effect=== | ||
* The most common side effects of [[SGLT2 inhibitors]] result from [[glucosuria]] and include: <ref name="pmid32865377">{{cite journal| author=Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P | display-authors=etal| title=Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 15 | pages= 1413-1424 | pmid=32865377 | doi=10.1056/NEJMoa2022190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32865377 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=33197352 Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51] </ref> | * The most common [[side effects]] of [[SGLT2 inhibitors]] result from [[glucosuria]] and include: <ref name="pmid32865377">{{cite journal| author=Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P | display-authors=etal| title=Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. | journal=N Engl J Med | year= 2020 | volume= 383 | issue= 15 | pages= 1413-1424 | pmid=32865377 | doi=10.1056/NEJMoa2022190 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32865377 }} [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=33197352 Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51] </ref> | ||
*[[Genital fungal infections]] (e.g. [[vaginal candidiasis]]) | *[[Genital fungal infections]] (e.g. [[vaginal candidiasis]]) | ||
*[[Urinary tract infection]] | *[[Urinary tract infection]] | ||
Latest revision as of 15:46, 29 September 2021
Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D.; Associate Editor(s)-In-Chief: Mitra Chitsazan, M.D.[1]
Overview
Sodium-glucose co-transporter 2 (SGLT2) inhibitors (dapagliflozin or empagliflozin) are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.
Sodium-glucose co-transporter 2 inhibitors
Indications for Sodium-glucose co-transporter 2 inhibitors
According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, all patients should be on a Sodium-glucose co-transporter 2 inhibitors if: [1]
1. The left ventricular ejection fraction (LVEF) is ≤ 40%
AND
2. The patient is already taking an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist.
- SGLT2 inhibitors should be administered for all patients with HFrEF regardless of diabetes status.
Background
- In DAPA-HF trial- a phase 3, placebo-controlled trial- 4744 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive dapagliflozin (10 mg once daily) or placebo, in addition to OMT [2]. The primary outcome was a composite of worsening HF (hospitalization or an urgent visit resulting in i.v. therapy for HF) or cardiovascular (CV) death. Results showed that over a median of 18.2 months, dapagliflozin resulted in a 26% reduction in the primary endpoint. Similar benefits were seen in patients with and without diabetes.
- In the EMPEROR-Reduced trial, 3730 patients with NYHA class II–IV, and an LVEF ≤40% despite optimal medical therapy (OMT) were randomly assigned to receive empagliflozin (10 mg once daily) or placebo, in addition to OMT [3]. The primary outcome was a composite of CV death or hospitalization for worsening HF. Results showed that over a median of 16 months empagliflozin reduced the primary endpoint by 25%.
- Therefore, dapagliflozin or empagliflozin are recommended for patients with HFrEF regardless of the presence or absence of diabetes, in addition to optimal medical therapy with an ACE-I/ARNI, a beta-blocker, and an aldosterone antagonist [1]
- SGLT2 inhibitors also have diuretic/natriuretic effects which may provide additional benefits in reducing volume overload and congestion and thus may allow a reduction in the need to loop diuretics.
Dosing
| SGLT2 inhibitor [1] | Starting dose | Target dose |
|---|---|---|
| Dapagliflozin | 10 mg QD | 10 mg QD |
| Empagliflozin | 10 mg QD | 10 mg QD |
Adverse effect
- The most common side effects of SGLT2 inhibitors result from glucosuria and include: [3]
- Genital fungal infections (e.g. vaginal candidiasis)
- Urinary tract infection
- Osmotic diuresis–related adverse events, such as volume depletion and a small reduction in eGFR following drug initiation.
- However, this effect is transient and reversible, and premature discontinuation of the drug is not needed.
References
- ↑ 1.0 1.1 1.2 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M; et al. (2021). "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure". Eur Heart J. 42 (36): 3599–3726. doi:10.1093/eurheartj/ehab368. PMID 34447992 Check
|pmid=value (help). - ↑ McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA; et al. (2019). "Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction". N Engl J Med. 381 (21): 1995–2008. doi:10.1056/NEJMoa1911303. PMID 31535829. Review in: Ann Intern Med. 2020 Feb 18;172(4):JC16
- ↑ 3.0 3.1 Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P; et al. (2020). "Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure". N Engl J Med. 383 (15): 1413–1424. doi:10.1056/NEJMoa2022190. PMID 32865377 Check
|pmid=value (help). Review in: Ann Intern Med. 2020 Nov 17;173(10):JC51