In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

Rao, Vishal N.; Murray, Evan; Butler, Javed; Cooper, Lauren B.; Cox, Zachary L.; Fiuzat, Mona; Green, Jennifer B.; Lindenfeld, Jo Ann; McGuire, Darren K.; Nassif, Michael E.; O’Brien, Cara; Pagidipati, Neha J.; Sharma, Kavita; Vaduganathan, Muthiah; Vardeny, Orly; Fonarow, Gregg C.; Mentz, Robert J.; Greene, Stephen J.

doi:10.1016/j.jacc.2021.08.064

Cited by 62 publications

(57 citation statements)

References 26 publications

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“…In contrast, patient discharged on GDMT are more likely to be adherent with these therapies following their discharge [ 20 ]. Hesitation to start SGLT2 inhibitors in patients hospitalized with AHF stems from concerns of adverse effects in these patients with a clinically tenuous status (e.g., hypotension, AKI, and hypoglycemia) [ 11 ]. The present meta-analysis demonstrates that initiating GDMT with SGLT2 inhibitor in patients with AHF during their hospitalizations or shortly thereafter (within 3 days of discharge) is safe and significantly reduces the risk of rehospitalization following discharge.…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy outcomes were chosen based on prior studies showing reduction in the risk of all-cause mortality and hospitalization for HF and improvement in KCCQ scale score in patients receiving SGLT2 inhibitors outside of the context of AHF [ 5 , 14 ]. Safety outcomes were chosen based on tolerability concerns related to AKI, hypotension, and hypoglycemia in the setting of initiation of SGLT2 inhibitors in AHF [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

“…Given the robust evidence supporting the use of SGLT2 inhibitors in patients with HFrEF, the updated American and European guidelines in 2021 included SGLT2 inhibitors in the guideline-directed medical therapies (GDMT) for chronic HFrEF [ 9 , 10 ]. In contrast, data regarding initiation of SGLT2 inhibitors among patients hospitalized with acute HF are more limited, and relative uncertainty regarding safety, tolerability, and efficacy with in-hospital initiation may cause clinicians to defer initiation of SGLT2 inhibitors to the outpatient setting [ 11 ]. This underscores the importance of evaluating the efficacy and safety of SGLT2 inhibitor initiation in patients hospitalized for AHF.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

Salah

Al’Aref

Khan

et al. 2022

Cardiovasc Diabetol

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Background There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF. Methods PubMed/Medline, Embase, and Cochrane library were searched using the following terms: (“sglt2" and "acute heart failure") and (“sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated. Results Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]). Conclusion Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

Salah

Al’Aref

Khan

et al. 2022

Cardiovasc Diabetol

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“…HF guidelines, consensus statements and clinical experts now advocate for in-hospital, rapid sequence initiation of core GDMT including BBs, ACEIs/ARBs/ARNIs, MRAs, and SGLT2Is. 4,7,15,[33][34][35] A goal for patients with HFrEF hospitalised with ADHF is to achieve initiation or continuation of all four classes of GDMT by hospital discharge in appropriate patients (Figure 2A). However, achievement of this goal will require significant changes to the conventional approach to GDMT optimisation.…”

Section: In-hospital Gdmt Initiation and Titrationmentioning

confidence: 99%

In-hospital Initiation and Up-titration of Guideline-directed Medical Therapies for Heart Failure with Reduced Ejection Fraction

et al. 2022

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Implementation of guideline-directed medical therapy for patients with heart failure is suboptimal. The use of guideline-directed medical therapy improves minimally after heart failure hospitalisation, despite this event clearly indicating increased risk of further hospitalisation and death. In-hospital initiation and titration of guideline-directed medical therapies is one potential strategy to fill these gaps in care, both in the acute vulnerable period after hospital discharge and in the long term. The purpose of this article is to review the knowledge gaps in best practices of in-hospital initiation and up-titration of guideline-directed medical therapies, the benefits and risks of in-hospital initiation and post-discharge focused titration of guideline-directed medical therapies, the recent literature evaluating these practices, and propose strategies to apply these principles to the care of patients with heart failure with reduced ejection fraction.

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“…In the DAPA-HF trial, a reduction of 49% in the composite outcome of cardiovascular death or worsening heart failure was noted 28 days after drug initiation [ 63 ]. Given the rapid clinical effect, initiating SGLT2i therapy during heart failure hospitalization has been advocated [ 64 ].…”

Section: Sodium-glucose Cotransporter-2 Inhibitors (Sglt2i)mentioning

confidence: 99%

The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients

Mazin

Chernomordik

Fefer

et al. 2022

JCM

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It is estimated that in the past two decades the number of patients diagnosed with diabetes mellites (DM) has doubled. Despite significant progress in the treatment of cardiovascular disease (CVD), including novel anti-platelet agents, effective lipid-lowering medications, and advanced revascularization techniques, patients with DM still are least twice as likely to die of cardiovascular causes compared with their non-diabetic counterparts, and current guidelines define patients with DM at the highest risk for atherosclerotic cardiovascular disease and major adverse cardiovascular events (MACE). Over the last few years, there has been a breakthrough in anti-diabetic therapeutics, as two novel anti-diabetic classes have demonstrated cardiovascular benefit with consistently reduced MACE, and for some agents, also improvement in heart failure status as well as reduced cardiovascular and all-cause mortality. These include the sodium-glucose cotransporter-2 inhibitors and the glucagon-like peptide-1 receptor agonists. The benefits of these medications are thought to be derived not only from their anti-diabetic effect but also from additional mechanisms. The purpose of this review is to provide the everyday clinician a detailed review of the various agents within each class with regard to their specific characteristics and the effects on MACE and cardiovascular outcomes.

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In-Hospital Initiation of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure With Reduced Ejection Fraction

Cited by 62 publications

References 26 publications

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

In-hospital Initiation and Up-titration of Guideline-directed Medical Therapies for Heart Failure with Reduced Ejection Fraction

The Impact of Novel Anti-Diabetic Medications on CV Outcomes: A New Therapeutic Horizon for Diabetic and Non-Diabetic Cardiac Patients

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