Meta-Analysis Assessing the Cardiovascular Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors According to Baseline Treatment of Interest

Abstract

Patients with diabetes mellitus (DM) feature an increased risk for both new-onset and recurrent heart failure (HF), 1 Kodama S Fujihara K Horikawa C Sato T Iwanaga M Yamada T Kato K Watanabe K Shimano H Izumi T Sone H Diabetes mellitus and risk of new-onset and recurrent heart failure: a systematic review and meta-analysis. ESC Heart Fail. 2020; 7: 2146-2174 Crossref Scopus (14) Google Scholar whereas women might experience an excess risk compared to men. 2 Ohkuma T Komorita Y Peters SAE Woodward M Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals. Diabetologia. 2019; 62: 1550-1560 Crossref PubMed Scopus (78) Google Scholar In those suffering from HF with reduced ejection fraction (HFrEF), angiotensin receptor-neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRAs) are considered as disease-modifying drugs, whereas diuretics are usually used to improve exercise capacity and decrease the risk of death and worsening HF. 3 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ Falk V González-Juanatey JR Harjola VP Jankowska EA Jessup M Linde C Nihoyannopoulos P Parissis JT Pieske B Riley JP Rosano GM Ruilope LM Ruschitzka F Rutten FH van der Meer P Authors/Task Force MembersDocument Reviewers2016 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 J Heart Fail. 2016; 18: 891-975 Crossref PubMed Scopus (4398) Google Scholar Diuretics also improve congestion in patients with HF with preserved ejection fraction (HFpEF). 3 Ponikowski P Voors AA Anker SD Bueno H Cleland JG Coats AJ Falk V González-Juanatey JR Harjola VP Jankowska EA Jessup M Linde C Nihoyannopoulos P Parissis JT Pieske B Riley JP Rosano GM Ruilope LM Ruschitzka F Rutten FH van der Meer P Authors/Task Force MembersDocument Reviewers2016 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 J Heart Fail. 2016; 18: 891-975 Crossref PubMed Scopus (4398) Google Scholar In this population, MRAs have been recently shown to decrease the risk for cardiovascular death and hospital re-admission for HF worsening. 4 Suzuki S Motoki H Kanzaki Y Maruyama T Hashizume N Kozuka A Yahikozawa K Kuwahara K Prognostic impact of mineralocorticoid receptor antagonist in patients with heart failure with preserved ejection fraction. ESC Heart Fail. 2020; 7: 2752-2761 Crossref Scopus (2) Google Scholar Unfortunately, the hallmark The Prospective Comparison of ARNI with ARB (angiotensin-receptor blockers) Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial failed to produce a significant result regarding the risk for the prespecified primary composite outcome (composite of total hospitalizations for HF and death from cardiovascular causes), questioning the role of ARNI in patients with HFpEF. 5 Solomon SD McMurray JJV Anand IS Ge J Lam CSP Maggioni AP Martinez F Packer M Pfeffer MA Pieske B Redfield MM Rouleau JL van Veldhuisen DJ Zannad F Zile MR Desai AS Claggett B Jhund PS Boytsov SA Comin-Colet J Cleland J Düngen HD Goncalvesova E Katova T Kerr Saraiva JF Lelonek M Merkely B Senni M Shah SJ Zhou J Rizkala AR Gong J Shi VC Lefkowitz MP PARAGON-HF Investigators and CommitteesAngiotensin-Neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019; 381: 1609-1620 Crossref PubMed Scopus (796) Google Scholar