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2 . 2021

Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of DAPA-HF

Abstract

Aims. Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of β-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial.

Methods and results. We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a β-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0–22.2) vs. 13.0 (12.1–14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21–1.72); p<0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48–0.93)] and without COPD [0.76 (0.65–0.87); interaction p-value 0.47].

Conclusions. In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD.

Clinical Trial Registration: ClinicalTrials.gov ID NCT03036124.

Keywords:heart failure, dapagliflozin, chronic obstructive pulmonary disease

Dewan P., Docherty K.F., Bengtsson O., de Boer R.A., Desai A.S., Drozdz J., Hawkins N.M., Inzucchi S.E., Kitakaze M., Køber L., Kosiborod M.N., Langkilde A.M., Lindholm D., Martinez F.A., Merkely B., Petrie M.C., Ponikowski P., Sabatine M.S., Schou M., Sjöstrand M., Solomon S.D., Verma S., Jhund P.S., McMurray J.J.V. Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of DAPA-HF. European Journal of Heart Failure. 2021; 23: 632–43. DOI: https://www.doi.org10.1002/ejhf.2083

Литература/References

1. Hawkins N.M., Petrie M.C., Jhund P.S., Chalmers G.W., Dunn F.G., McMurray J.J. Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail. 2009; 11: 130–9.

2. Pellicori P., Cleland J.G., Clark A.L. Chronic obstructive pulmonary disease and heart failure: a breathless conspiracy. Heart Fail Clin. 2020; 16: 33–44.

3. Jaiswal A., Chichra A., Nguyen V.Q., Gadiraju T.V., Le Jemtel T.H. Challenges in the management of patients with chronic obstructive pulmonary disease and heart failure with reduced ejection fraction. Curr Heart Fail Rep. 2016; 13: 30–6.

4. Staszewsky L., Wong M., Masson S., Barlera S., Carretta E., Maggioni A.P., Anand I.S., Cohn J.N., Tognoni G., Latini R.; Valsartan Heart Failure Trial Investigators. Clinical, neurohormonal, and inflammatory markers and overall prognostic role of chronic obstructive pulmonary disease in patients with heart failure: data from the Val-HeFT heart failure trial. J Card Fail. 2007; 13: 797–804.

5. Mentz R.J., Schulte P.J., Fleg J.L., Fiuzat M., Kraus W.E., Piña I.L., Keteyian S.J., Kitzman D.W., Whellan D.J., Ellis S.J., O’Connor C.M. Clinical characteristics, response to exercise training, and outcomes in patients with heart failure and chronic obstructive pulmonary disease: findings from Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION). Am Heart J. 2013; 165: 193–9.

6. Tavazzi L., Swedberg K., Komajda M., Böhm M., Borer J.S., Lainscak M., Robertson M., Ford I.; SHIFT Investigators. Clinical profiles and outcomes in patients with chronic heart failure and chronic obstructive pulmonary disease: an efficacy and safety analysis of SHIFT study. Int J Cardiol. 2013; 170: 182–8.

7. Neder J.A., Rocha A., Berton D.C., O’Donnell D.E. Clinical and physiologic implica- tions of negative cardiopulmonary interactions in coexisting chronic obstructive pulmonary disease-heart failure. Clin Chest Med. 2019; 40: 421–38.

8. Coiro S., Girerd N., Rossignol P., Ferreira J.P., Maggioni A., Pitt B., Tritto I., Ambrosio G., Dickstein K., Zannad F. Association of β-blocker treatment with mortality following myocardial infarction in patients with chronic obstructive pulmonary disease and heart failure or left ventricular dysfunction: a propensity matched-cohort analysis from the High-Risk Myocardial Infarction Database Initiative. Eur J Heart Fail. 2017; 19: 271–9.

9. Dransfield M.T., Voelker H., Bhatt S.P., Brenner K., Casaburi R., Come C.E., Cooper J.D., Criner G.J., Curtis J.L., Han M.L., Hatipoğlu U., Helgeson E.S., Jain V.V., Kalhan R., Kaminsky D., Kaner R., Kunisaki K.M., Lambert A.A., Lammi M.R., Lindberg S., Make B.J., Martinez F.J., McEvoy C., Panos R.J., Reed R.M., Scanlon P.D., Sciurba F.C., Smith A., Sriram P.S., Stringer W.W., Weingarten J.A., Wells J.M., Westfall E., Lazarus S.C., Connett J.E.; BLOCK COPD Trial Group. Metoprolol for the prevention of acute exacerbations of COPD. N EnglJ Med. 2019; 3811: 2304–14.

10. Singh J.M., Palda V.A., Stanbrooh M.B., Chapman K.R. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review. Arch Intern Med. 2002; 162: 2527–36.

11. García Morales O.M., Rojas-Reyes M.X., Dennis R.J. Oral xanthine derivatives (theo- phylline and doxofylline) for patients with stable chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. 2017; 2017: CD012748.

12. McMurray J.J., Solomon S.D., Inzucchi S.E., Køber L., Kosiborod M.N., Martinez F.A., Ponikowski P., Sabatine M.S., Anand I.S., Bělohlávek J., Böhm M., Chiang C.E., Chopra V.K., de Boer R.A., Desai A.S., Diez M., Drozdz J., Dukát A., Ge J., Howlett J.G., Katova T., Kitakaze M., Ljungman C.E., Merkely B., Nicolau J.C., O’Meara E., Petrie M.C., Vinh P.N., Schou M., Tereshchenko S., Verma S., Held C., DeMets D.L., Docherty K.F., Jhund P.S., Bengtsson O., Sjöstrand M., Langkilde A.M.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N EnglJ Med. 2019; 21: 1995–2008.

13. Packer M., Anker S.D., Butler J., Filippatos G., Pocock S.J., Carson P., Januzzi J., Verma S., Tsutsui H., Brueckmann M., Jamal W., Kimura K., Schnee J., Zeller C., Cotton D., Bocchi E., Böhm M., Choi D.J., Chopra V., Chuquiure E., Giannetti N., Janssens S., Zhang J., Gonzalez Juanatey J.R., Kaul S., Brunner-La Rocca H.P., Merkely B., Nicholls S.J., Perrone S., Pina I., Ponikowski P., Sattar N., Senni M., Seronde M.F., Spinar J., Squire I., Taddei S., Wanner C., Zannad F.; EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383: 1413–24.

14. Seferović P.M., Fragasso G., Petrie M., Mullens W., Ferrari R., Thum T., Bauersachs J., Anker S.D., Ray R., Çavuşoğlu Y., Polovina M., Metra M., Ambrosio G., Prasad K., Seferović J., Jhund P.S., Dattilo G., Čelutkiene J., Piepoli M., Moura B., Chioncel O., Gal T.B., Heymans S., Jaarsma T., Hill L., Lopatin Y., Lyon A.R., Ponikowski P., Lainščak M., Jankowska E., Mueller C., Cosentino F., Lund L.H., Filippatos G.S., Ruschitzka F., Coats A.J., Rosano G.M. Heart Failure Association of the European Society of Cardiology update on sodium- glucose co-transporter 2 inhibitors in heart failure. Eur J Heart Fail. 2020; 22: 1984–6.

16. McMurray J.J., DeMets D.L., Inzucchi S.E., Køber L., Kosiborod M.N., Langkilde A.M., Martinez F.A., Bengtsson O., Ponikowski P., Sabatine M.S., Sjöstrand M., Solomon S.D.; 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: 665–75.

17. McMurray J.J., DeMets D.L., Inzucchi S.E., Køber L., Kosiborod M.N., Langkilde A.M., Martinez F.A., Bengtsson O., Ponikowski P., Sabatine M.S., Sjöstrand M., Solomon S.D.; 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: 1402–11.

18. World Medical Association. Human experimentation code of ethics of the World Medical Association. Br Med J. 1964; 2: 177.

19. Green C.P., Porter C.B., Bresnahan D.R., Spertus J.A. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000; 35: 1245–55.

20. Hawkins N.M., Wang D., Petrie M.C., Pfeffer M.A., Swedberg K., Granger C.B., Yusuf S., Solomon S.D., Östergren J., Michelson E.L., Pocock S.J., Maggioni A.P., McMurray J.J.; CHARM Investigators and Committees. Baseline characteristics and outcomes of patients with heart failure receiving bronchodilators in the CHARM programme. Eur J Heart Fail. 2010; 12: 557–65.

21. Canepa M., Temporelli P.L., Rossi A., Gonzini L., Nicolosi G.L., Staszewsky L., Marchioli R., Maggioni A.P., Tavazzi L.; GISSI-HF Investigators. Prevalence and prognostic impact of chronic obstructive pulmonary disease in patients with chronic heart failure: data from the GISSI-HF trial. Cardiology. 2017; 136: 128–37.

22. Mentz R.J., Schmidt P.H., Kwasny M.J., Ambrosy A.P., O’Connor C.M., Konstam M.A., Zannad F., Maggioni A.P., Swedberg K., Gheorghiade M. The impact of chronic obstructive pulmonary disease in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST trial. J Card Fail. 2012; 18: 515–23.

23. Canepa M., Straburzynska-Migaj E., Drozdz J., Fernandez-Vivancos C., Pinilla J.M., Nyolczas N., Temporelli P.L., Mebazaa A., Lainscak M., Laroche C., Maggioni A.P., Piepoli M.F., Coats A.J., Ferrari R., Tavazzi L.; ESC-HFA Heart Failure Long-Term Registry Investigators. Characteristics, treatments and 1-year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long-Term Registry. Eur J Heart Fail. 2018; 20: 100–10.

24. Fonarow G.C., Yancy C.W., Albert N.M., Curtis A.B., Stough W.G., Gheorghiade M., Heywood J.T., McBride M.L., Mehra M.R., O’Connor C.M., Reynolds D., Walsh M.N. Heart failure care in the outpatient cardiology practice setting: findings from IMPROVE HF. Circ Heart Fail. 2008; 1: 98–106.

25. Kubota Y., Tay W.T., Asai K., Murai K., Nakajima I., Hagiwara N., Ikeda T., Kurita T., Teng T.H., Anand I., Lam C.S., Shimizu W.; ASIA-HF Study Investigators. Chronic obstructive pulmonary disease and β-blocker treatment in Asian patients with heart failure. ESC Heart Fail. 2018; 5: 297–305.

26. Mtisi T.F., Frishman W.H. Beta adrenergic blocker use in patients with chronic obstructive pulmonary disease and concurrent chronic heart failure with a low ejection fraction. Cardiol Rev. 2020; 28: 20–5.

27. Canepa M., Franssen F.M., Olschewski H., Lainscak M., Böhm M., Tavazzi L., Rosenkranz S. Diagnostic and therapeutic gaps in patients with heart failure and chronic obstructive pulmonary disease. JACC Heart Fail. 2019; 7: 823–33.

28. AbdelHalim H.A., AboElNaga H.H. Is renal impairment an anticipated COPD comorbidity? Respir Care. 2016; 61: 1201–6.

29. Neder J.A., Rocha A., Alencar M.C., Arbex F., Berton D.C., Oliveira M.F., Sperandio P.A., Nery L.E., O’Donnell D.E. Current challenges in managing comorbid heart failure and COPD. Expert Rev Cardiovasc. 2018; 16: 653–73.

30. Hawkins N.M., Petrie M.C., MacDonald M.R., Jhund P.S., Fabbri L.M., Wikstrand J., McMurray J.J. Heart failure and chronic obstructive pulmonary disease: the quandary of beta-blockers and β-agonists. J Am Coll Cardiol. 2011; 57: 2127 –38.

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CHIEF EDITOR
CHIEF EDITOR
Andrey G. Obrezan
MD, Professor, Head of the Hospital Therapy Department of the Saint Petersburg State University, Chief Physician of SOGAZ MEDICINE Clinical Group, St. Petersburg, Russian Federation

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