Efficacy and safety of digoxin in patients with heart failure and reduced ejection fraction according to diabetes status: An analysis of the Digitalis Investigation Group (DIG) trial

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events. Methods: Patients with class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes. Results: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (HbA1c 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio 0.72 [95% CI 0.60-0.87] and 0.78 [95% CI 0.64-0.97], respectively, interaction P =0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these endpoints, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia. Conclusions: In the EMPEROR-Reduced trial, empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.

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Efficacy and Safety of Different Aerobic Exercise Intensities in Patients With Heart Failure With Reduced Ejection Fraction: Design of a Multicenter Randomized Controlled Trial (HF-EI Trial)

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.705972 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ting Shen ◽

Xiaoling Liu ◽

Bo Zhuang ◽

Qian Luo ◽

Yishan Jin ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Aerobic Exercise ◽

Exercise Intensity ◽

Control Group ◽

Efficacy And Safety ◽

Reduced Ejection Fraction ◽

Clinical Events ◽

Patients With Heart Failure ◽

Intensity Training

Background: Heart failure (HF) is one of the major causes of mortality worldwide, representing the terminal stage of several cardiovascular diseases. Exercise-based rehabilitation is a beneficial therapy for patients with chronic heart failure (CHF). However, there is a lack of specific guidance on clinical decision-making regarding optimal exercise intensity. It is necessary to optimize the clinical recommendations for HF exercises. We will evaluate the efficacy and safety of different aerobic exercise intensities in patients with heart failure with reduced ejection fraction (HFrEF): the HF-EI trial. This trial aims to assess the appropriate exercise intensity for patients with HFrEF.Methods: After a baseline assessment to determine the safety of exercise, 180 patients will be randomly assigned to supervised high-intensity exercise training (ET) group, supervised moderate intensity training (MIT) group, and control group at a ratio of 1:1:1. Patients randomly receiving high intensity training (HIT) undergo supervised ET (3 times/week, 30 min) for aerobic endurance at 70% peak oxygen consumption (peak VO2) intensity for 12 weeks. The MIT patients will perform supervised aerobic ET (3 times/week, 35–42 min) at the anaerobic threshold (AT) intensity for 12 weeks. The control group will continue to maintain their daily activities and will not receive ET. During the baseline and follow-up period, physical examination, laboratory tests, cardiology diagnostic tests, cardiopulmonary exercise tests (CPET), 6-min walk distance (6MWD), scale scores, exercise steps, medications, and clinical events will be monitored. Throughout the research, sport bracelets and patient diaries will be used to monitor and record overall physical activity, training courses, and compliance.Discussion: The HF-EI trial will evaluate the effects of different aerobic exercise intensities on peak VO2, quality of life (QoL), and clinical events among patients with HFrEF. The findings of this trial will provide a basis for formulating exercise prescriptions for patients with HFrEF.Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2000036381.

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The Role of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure, Regardless of Diabetes Status: Focus on Cardiovascular Disease

Annals of Pharmacotherapy ◽

10.1177/1060028020985111 ◽

2021 ◽

pp. 106002802098511

Author(s):

Filipe Ferrari ◽

Vítor M. Martins ◽

Rafael S. Scheffel ◽

Anderson D. da Silveira ◽

Marcelo Trotte Motta ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Data Extraction ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Reduced Ejection Fraction ◽

Sodium Glucose Cotransporter ◽

Diabetes Status ◽

Neprilysin Inhibitor ◽

Patients With Heart Failure

Objective: To provide clinical guidance and an overview of the available data on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF), regardless of the presence of type 2 diabetes mellitus (T2DM). Data Sources: We searched the MEDLINE database via PubMed (from January 2015 to November 2020) for the following key terms: SGLT2 inhibitors, sodium-glucose co-transporter-2 inhibitors, SGLT2i, heart failure, and heart failure with reduced ejection fraction. Study Selection and Data Extraction: To be included in the review, the articles needed to assess the effects of SGLT2 inhibitors in the heart failure (HF) scenario. Data Synthesis: There is consistent evidence that SGLT2 inhibitors reduce the risk of major adverse cardiovascular (CV) events and hospitalization in patients with HFrEF, even in the absence of T2DM. On May 5, 2020, the U.S. Food and Drug Administration approved dapagliflozin for adults with HFrEF, regardless of the presence of T2DM, even in those patients on standard therapy, including an angiotensin receptor/neprilysin inhibitor. Relevance to Patient Care and Clinical Practice: The SGLT2 inhibitors are well tolerated, and their once-daily dosing without the need for adjustments is convenient. These drugs can be considered a major breakthrough in pharmacotherapy for HF, providing physicians with a new treatment approach to reduce major clinical outcomes. Conclusions: SGLT2 inhibitor therapy reduces CV death and hospitalizations in HFrEF patients regardless of T2DM. The decision to prescribe this class of drugs should not be determined by glycemic status.

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