Tag: SGLT2

Sodium-Glucose Cotransporter Inhibitors in Heart Failure

LITERATURE REVIEW

                

Hema Manvi Koneru, MBBS,
Rajiv Gandhi Institute of Medical Sciences, Telangana, India

Divyasri Koneru, MBBS,
Dr.Pinnamaneni Siddartha Institute of Medical Sciences and Research Foundation, Andhra Pradesh, India.

Amanpreet Kaur, MBBS,
Government Medical College, Patiala, Punjab, India.

Amin H. Karim MD
Baylor College of Medicine, Houston, Texas

⁠⁠Introduction

Heart failure (HF) is a prevalent and serious condition associated with substantial morbidity and mortality. Management strategies have evolved, with recent focus on sodium-glucose cotransporter 2 (SGLT2) inhibitors potentially offering novel therapeutic benefits.

SGLT2 Inhibitors in HF with Reduced Ejection Fraction (HFrEF)

Studies have demonstrated that dapagliflozin, an SGLT2 inhibitor, significantly reduces the risk of worsening HF or cardiovascular death in patients with HFrEF. (1,3) The DAPA-HF trial, a pivotal phase 3 study, enrolled patients with New York Heart Association (NYHA) class II-IV symptoms and ejection fractions ≤ 40%. Results showed a reduction in the primary outcome (composite of worsening HF or cardiovascular death) among those treated with dapagliflozin compared to placebo (HR 0.74, 95% CI 0.65-0.85). This benefit was observed regardless of diabetes status, highlighting potential glucose-independent mechanisms of action.

SGLT2 Inhibitors in HF with Mildly Reduced or Preserved Ejection Fraction

Emerging evidence suggests that dapagliflozin may also benefit patients with HF and preserved or mildly reduced ejection fraction (HFpEF and HFmrEF). (2) The DELIVER trial randomized patients with HF and ejection fractions > 40% to dapagliflozin or placebo. Results indicated a reduction in the composite of worsening HF or cardiovascular death with dapagliflozin (HR 0.82, 95% CI 0.73-0.92). Moreover, improvements in symptom burden were noted, supporting potential broad utility across HF phenotypes.

Mechanisms of Action

Beyond glycemic control, SGLT2 inhibitors like dapagliflozin may exert beneficial effects in HF through mechanisms including improved cardiac remodeling, reduced sodium retention, decrease plasma volume, and potential metabolic modulation. These mechanisms contribute to improved hemodynamics and reduced cardiovascular morbidity and mortality, as observed in clinical trials.

Contraindication

  • eGFR < 30mL/minute/1.73 m2

Safety and Tolerability

Safety profiles across trials indicate that dapagliflozin is generally well tolerated in HF patients, with adverse event rates comparable to placebo. Common side effects include volume depletion and renal dysfunction (Acute kidney injury due to dehydration), which are manageable with appropriate monitoring. Other severe side effects are euglycemic diabetic ketoacidosis, allergic reaction and genital infections (mostly fungal).

  • Canagliflozin increase the risk of lower limb amputation and bone fractures.

Clinical Implications and Future Directions

The efficacy of SGLT2 inhibitors in reducing HF-related events underscores their potential as adjunctive therapy in standard HF management. Future research should focus on optimizing patient selection, exploring combination therapies, and elucidating long-term benefits and risks in diverse patient populations.

Conclusion

SGLT2 inhibitors like dapagliflozin show great promise in improving outcomes for patients with heart failure. These medications not only reduce cardiovascular risks but also improve quality of life, highlighting their potential as essential elements of comprehensive heart failure treatment strategies.

References

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