Vol 6, No 4 (2021)
Review article
Published online: 2021-11-25

open access

Page views 6029
Article views/downloads 455
Get Citation

Connect on Social Media

Connect on Social Media

Dapagliflozin — a key pawn on the new guidelines chessboard

Jacek Kubica1
Medical Research Journal 2021;6(4):342-350.

Abstract

Treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) aims to reduce mortality, prevent rehospitalizations due to heart failure (HF) exacerbation, and improve the clinical status, functional capacity, and quality of life. All these goals were achieved in the DAPA-HF trial. In this trial, the reduction in the primary outcome, defined as a composite of worsening of HF or cardiovascular death, was achieved in patients receiving dapagliflozin [hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.65–0.85; p < 0.001) as compared with placebo. In addition, the beneficial effect of dapagliflozin on the primary outcome was generally consistent across prespecified subgroups regardless of baseline treatment, diagnosis of diabetes, or left ventricular ejection fraction (LVEF).
Data from multiple countries was obtained in the CVD-REAL study. The use of different sodium-glucose
co-transporter 2 (SGLT2) inhibitors, versus other glucose-lowering drugs, was associated with lower rates of hospitalization for HF (HR 0.61; 95% CI 0.51–0.73; p < 0.001) and death (HR 0.49; 95% CI 0.41–0.57; p < 0.001). These findings were confirmed in the CVD-REAL-2 study.
The exceptional clinical benefits of SGLT2 inhibitors applied on top of the previously guideline recommended treatment in patients with chronic HFrEF led to fundamental changes in the recommended treatment strategy proposed in the 2016 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic HF.
To conclude, the new treatment algorithm for HFrEF is based on the findings of many groundbreaking trials. However, it is the results of trials with SGLT2 inhibitors, applied in patients with HFrEF on top of the optimal treatment including an implantable cardioverter-defibrillator and/or cardiac resynchronization therapy, that have fundamentally changed the strategy of treatment.

Article available in PDF format

View PDF Download PDF file

References

  1. Lytvyn Y, Bjornstad P, Udell JA, et al. Sodium glucose cotransporter-2 inhibition in heart failure: potential mechanisms, clinical applications, and summary of clinical trials. Circulation. 2017; 136(17): 1643–1658.
  2. Dekkers CCJ, Sjöström CD, Greasley PJ, et al. Effects of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on estimated plasma volume in patients with type 2 diabetes. Diabetes Obes Metab. 2019; 21(12): 2667–2673.
  3. Kubica J, Kubica A, Grzelakowska K, et al. Inhibitors of sodium-glucose transport protein 2: A new multidirectional therapeutic option for heart failure patients. Cardiol J. 2021 [Epub ahead of print].
  4. Soga F, Tanaka H, Tatsumi K, et al. Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure. Cardiovasc Diabetol. 2018; 17(1): 132.
  5. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014; 124(2): 499–508.
  6. Carlström M, Wilcox CS, Arendshorst WJ. Renal autoregulation in health and disease. Physiol Rev. 2015; 95(2): 405–511.
  7. McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021; 42(36): 3599–3726.
  8. McMurray JJV, Solomon SD, Inzucchi SE, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019; 381(21): 1995–2008.
  9. McMurray JJV, DeMets DL, Inzucchi SE, et al. DAPA-HF Committees and Investigators. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019; 21(11): 1402–1411.
  10. McMurray JJV, DeMets DL, Inzucchi SE, et al. DAPA-HF Committees and Investigators. A trial to evaluate the effect of the sodium-glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019; 21(5): 665–675.
  11. Bhatt DL, Verma S, Braunwald E. The DAPA-HF trial: a momentous victory in the war against heart failure. Cell Metab. 2019; 30(5): 847–849.
  12. Dewan P, Solomon SD, Jhund PS, et al. DAPA-HF Investigators and Committees. Efficacy and safety of sodium-glucose co-transporter 2 inhibition according to left ventricular ejection fraction in DAPA-HF. Eur J Heart Fail. 2020; 22(7): 1247–1258.
  13. Petrie MC, Verma S, Docherty KF, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020; 323(14): 1353–1368.
  14. Jackson AM, Dewan P, Anand IS, et al. Dapagliflozin and diuretic use in patients with heart failure and reduced ejection fraction in DAPA-HF. Circulation. 2020; 142(11): 1040–1054.
  15. Docherty KF, Jhund PS, Bengtsson O, et al. DAPA-HF Investigators and Committees. Effect of dapagliflozin in DAPA-HF according to background glucose-lowering therapy. Diabetes Care. 2020; 43(11): 2878–2881.
  16. Solomon SD, Jhund PS, Claggett BL, et al. Effect of dapagliflozin in patients with hfref treated with sacubitril/valsartan: the DAPA-HF trial. JACC Heart Fail. 2020; 8(10): 811–818.
  17. Yeoh SE, Dewan P, Jhund PS, et al. DAPA-HF Investigators and Committees. Patient characteristics, clinical outcomes, and effect of dapagliflozin in relation to duration of heart failure: is it ever too late to start a new therapy? Circ Heart Fail. 2020; 13(12): e007879.
  18. Kosiborod MN, Jhund PS, Docherty KF, et al. Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial. Circulation. 2020; 141(2): 90–99.
  19. Nassif ME, Windsor SL, Tang F, et al. Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF trial. Circulation. 2019; 140(18): 1463–1476.
  20. Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020; 396(10254): 819–829.
  21. Kosiborod M, Cavender MA, Fu AZ, et al. CVD-REAL Investigators and Study Group*. Lower risk of heart failure and death in patients initiated on sodium-glucose cotransporter-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL study (comparative effectiveness of cardiovascular outcomes in new users of sodium-glucose cotransporter-2 inhibitors). Circulation. 2017; 136(3): 249–259.
  22. Kosiborod M, Lam CSP, Kohsaka S, et al. CVD-REAL Investigators and Study Group. Cardiovascular events associated with SGLT-2 inhibitors versus other glucose-lowering drugs: the CVD-REAL 2 study. J Am Coll Cardiol. 2018; 71(23): 2628–2639.
  23. Ponikowski P, Voors AA, Anker SD, et al. ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016; 37(27): 2129–2200.
  24. Packer M, Anker SD, Butler J, et al. EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383(15): 1413–1424.
  25. Kubica J. Heart failure treatment according to the 2021 European Society of Cardiology Guidelines — experiences with SGLT2 inhibitors have changed the treatment strategy. Medical Research Journal. 2021; 6(3): 163–165.
  26. Gager GM, von Lewinski D, Sourij H, et al. Effects of SGLT2 inhibitors on ion homeostasis and oxidative stress associated mechanisms in heart failure. Biomed Pharmacother. 2021; 143: 112169.
  27. Buszko K, Obońska K, Michalski P, et al. The Adherence Scale in Chronic Diseases (ASCD). The power of knowledge: the key to successful patient — health care provider cooperation. Med Res J. 2016; 1(1): 37–42.
  28. Kubica A, Kosobucka A, Michalski P, et al. The Adherence in Chronic Diseases Scale — a new tool to monitor implementation of a treatment plan. Folia Cardiol. 2017; 12(1): 19–26.
  29. Kubica A, Obońska K, Fabiszak T, et al. Adherence to antiplatelet treatment with P2Y12 receptor inhibitors. Is there anything we can do to improve it? A systematic review of randomized trials. Curr Med Res Opin. 2016; 32(8): 1441–1451.
  30. Kubica A, Pietrzykowski Ł. The therapeutic plan implementation in patients discharged from the hospital after myocardial infarction. Med Res J. 2021; 6(2): 79–82.
  31. Kosobucka A, Pietrzykowski Ł, Michalski P, et al. Impact of readiness for discharge from the hospital on the implementation of the therapeutic plan. Med Res J. 2020; 5(4): 256–264.
  32. Kubica A. Self-reported questionnaires for a comprehensive assessment of patients after acute coronary syndrome. Med Res J. 2019; 4(2): 106–109.
  33. Kubica A, Gruchała M, Jaguszewski M, et al. Adherence to treatment — a pivotal issue in long-term treatment of patients with cardiovascular diseases. An expert standpoint. Med Res J. 2018; 2(4): 123–127.
  34. Kubica A, Kosobucka A, Michalski P, et al. Self-reported questionnaires for assessment adherence to treatment in patients with cardiovascular diseases. Med Res J. 2018; 2(4): 115–122.
  35. Buszko K, Pietrzykowski Ł, Michalski P, et al. Validation of the Functioning in Chronic Illness Scale (FCIS). Med Res J. 2018; 3(2): 63–69.
  36. Buszko K, Kosobucka A, Michalski P, et al. The readiness for hospital discharge of patients after acute myocardial infarction: a new self-reported questionnaire. Med Res J. 2017; 2(1): 20–28.
  37. Yusuf S, Pitt B, Davis CE, et al. SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991; 325(5): 293–302.
  38. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999; 353(9146): 9–13.
  39. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341(10): 709–717.
  40. Cohn JN, Tognoni G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001; 345(23): 1667–1675.
  41. Poole-Wilson PA, Swedberg K, Cleland JGF, et al. Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003; 362(9377): 7–13.
  42. Young JB, Dunlap ME, Pfeffer MA, et al. Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Investigators and Committees. Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004; 110(17): 2618–2626.
  43. Zannad F, McMurray JJV, Krum H, et al. EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011; 364(1): 11–21.
  44. McMurray JJV, Packer M, Desai AS, et al. PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371(11): 993–1004.