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Update on the Impact of Comorbidities on the Efficacy and Safety of Heart Failure Medications

  • Comorbidities of Heart Failure (J. Tromp, Section Editor)
  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Multiple newer medications benefit patients with heart failure with reduced ejection fraction (HFrEF). While these therapies benefit the broad population with HFrEF, the efficacy and safety of these therapies have been less well characterized in patients with significant comorbidities.

Recent Findings

Common comorbidities of high interest in heart failure (HF) include diabetes mellitus, chronic kidney disease (CKD), atrial fibrillation, and obesity, and each has potential implications for clinical management. As the burden of comorbidities increases in HF populations, risk-benefit assessments of HF therapies in the context of different comorbidities are increasingly relevant for clinical practice. This review summarizes data regarding the core HFrEF therapies in the context of comorbidities, with specific attention to sodium-glucose cotransporter 2 inhibitors, sacubitril/valsartan, mineralocorticoid receptor antagonists (MRAs), and beta-blockers. In general, studies support consistent treatment effects with regard to clinical outcome benefits in the presence of comorbidities. Likewise, safety profiles are relatively consistent irrespective of comorbidities, with the exception of heightened risk of hyperkalemia with MRA therapy in patients with severe CKD.

Summary

In conclusion, while HF management is complex in the context of multiple comorbidities, the totality of evidence strongly supports guideline-directed medical therapies as foundational for improving outcomes in these high-risk patients.

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References

  1. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2020 Update: a report from the American Heart Association. Circulation. 2020;141:e139–596.

    Article  PubMed  Google Scholar 

  2. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6:606–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Khan MS, Samman Tahhan A, Vaduganathan M, Greene SJ, Alrohaibani A, Anker SD, et al. Trends in prevalence of comorbidities in heart failure clinical trials. Eur J Heart Fail. 2020;22:1032–42.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sharma A, Zhao X, Hammill BG, et al. Trends in noncardiovascular comorbidities among patients hospitalized for heart failure: insights from the Get With The Guidelines-Heart Failure Registry. Circ Heart Fail. 2018;11:e004646.

    Article  PubMed  Google Scholar 

  5. Lee CS, Chien CV, Bidwell JT, Gelow JM, Denfeld QE, Creber RM, et al. Comorbidity profiles and inpatient outcomes during hospitalization for heart failure: an analysis of the U.S. Nationwide inpatient sample. BMC Cardiovasc Disord. 2014;14:73.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ather S, Chan W, Bozkurt B, Aguilar D, Ramasubbu K, Zachariah AA, et al. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012;59:998–1005.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mentz RJ, Felker GM. Noncardiac comorbidities and acute heart failure patients. Heart Fail Clin. 2013;9:359–67 vii.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bhatt AS, Ambrosy AP, Dunning A, DeVore AD, Butler J, Reed S, et al. The burden of non-cardiac comorbidities and association with clinical outcomes in an acute heart failure trial - insights from ASCEND-HF. Eur J Heart Fail. 2020;22:1022–31.

    Article  PubMed  Google Scholar 

  9. Dunlay SM, Givertz MM, Aguilar D, Allen LA, Chan M, Desai AS, et al. Type 2 diabetes mellitus and heart failure: a scientific statement from the American Heart Association and the Heart Failure Society of America: This statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update. Circulation. 2019;140:e294–324.

    Article  CAS  PubMed  Google Scholar 

  10. Triposkiadis F, Giamouzis G, Parissis J, Starling RC, Boudoulas H, Skoularigis J, et al. Reframing the association and significance of co-morbidities in heart failure. Eur J Heart Fail. 2016;18:744–58.

    Article  PubMed  Google Scholar 

  11. Nichols GA, Reynolds K, Kimes TM, Rosales AG, Chan WW. Comparison of risk of re-hospitalization, all-cause mortality, and medical care resource utilization in patients with heart failure and preserved versus reduced ejection fraction. Am J Cardiol. 2015;116:1088–92.

    Article  PubMed  Google Scholar 

  12. von Haehling S, van Veldhuisen DJ, Roughton M, Babalis D, de Boer RA, Coats AJS, et al. Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study. Eur J Heart Fail. 2011;13:656–63.

    Article  Google Scholar 

  13. Yancy CW, Lopatin M, Stevenson LW, de Marco T, Fonarow GC, ADHERE Scientific Advisory Committee and Investigators. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006;47(1):76–84. https://doi.org/10.1016/j.jacc.2005.09.022.

  14. Tuegel C, Bansal N. Heart failure in patients with kidney disease. Heart. 2017;103:1848–53.

    Article  CAS  PubMed  Google Scholar 

  15. Kajimoto K, Sato N, Takano T, investigators of the Acute Decompensated Heart Failure Syndromes r. Relation of left ventricular ejection fraction and clinical features or co-morbidities to outcomes among patients hospitalized for acute heart failure syndromes. Am J Cardiol. 2015;115:334–40.

    Article  PubMed  Google Scholar 

  16. Lenzen MJ, Scholte op Reimer WJ, Boersma E, et al. Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey. Eur Heart J. 2004;25:1214–20.

    Article  CAS  PubMed  Google Scholar 

  17. Carlisle MA, Fudim M, DeVore AD, Piccini JP. Heart failure and atrial fibrillation, like fire and fury. JACC Heart Fail. 2019;7:447–56.

    Article  PubMed  Google Scholar 

  18. Filippatos G, Teerlink JR, Farmakis D, Cotter G, Davison BA, Felker GM, et al. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur Heart J. 2014;35:1041–50.

    Article  CAS  PubMed  Google Scholar 

  19. Chiang CE, Naditch-Brule L, Murin J, et al. Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry. Circ Arrhythm Electrophysiol. 2012;5:632–9.

    Article  PubMed  Google Scholar 

  20. Santhanakrishnan R, Wang N, Larson MG, Magnani JW, McManus DD, Lubitz SA, et al. Atrial fibrillation begets heart failure and vice versa: temporal associations and differences in preserved versus reduced ejection fraction. Circulation. 2016;133:484–92.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Digitalis Investigation G. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–33.

    Article  Google Scholar 

  22. Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114:397–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012;126:65–75.

    Article  PubMed  Google Scholar 

  24. Lavie CJ, Alpert MA, Arena R, Mehra MR, Milani RV, Ventura HO. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail. 2013;1:93–102.

    Article  PubMed  Google Scholar 

  25. Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:305–13.

    Article  PubMed  Google Scholar 

  26. Hawkins NM, Virani S, Ceconi C. Heart failure and chronic obstructive pulmonary disease: the challenges facing physicians and health services. Eur Heart J. 2013;34:2795–803.

    Article  PubMed  Google Scholar 

  27. Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, et al. Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol. 2003;41(2):217–23. https://doi.org/10.1016/s0735-1097(02)02696-7.

  28. van Deursen VM, Urso R, Laroche C, Damman K, Dahlström U, Tavazzi L, et al. Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail. 2014;16:103–11.

    Article  PubMed  Google Scholar 

  29. Agarwal SK, Heiss G, Barr RG, Chang PP, Loehr LR, Chambless LE, et al. Airflow obstruction, lung function, and risk of incident heart failure: the Atherosclerosis Risk in Communities (ARIC) study. Eur J Heart Fail. 2012;14(4):414–22. https://doi.org/10.1093/eurjhf/hfs016.

  30. Greene SJ, Vaduganathan M, Khan MS, Bakris GL, Weir MR, Seltzer JH, et al. Prevalent and incident heart failure in cardiovascular outcome trials of patients with type 2 diabetes. J Am Coll Cardiol. 2018;71(12):1379–90. https://doi.org/10.1016/j.jacc.2018.01.047.

  31. Shah AD, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol. 2015;3(2):105–13. https://doi.org/10.1016/S2213-8587(14)70219-0.

  32. Anker SD, Butler J, Filippatos G et al. Effect of Empagliflozin on cardiovascular and renal outcomes in patients with heart failure by baseline diabetes status - results from the EMPEROR-Reduced Trial. Circulation 2020.

  33. Zafrir B, Lund LH, Laroche C, Ruschitzka F, Crespo-Leiro MG, Coats AJS, et al. Prognostic implications of atrial fibrillation in heart failure with reduced, mid-range, and preserved ejection fraction: a report from 14 964 patients in the European Society of Cardiology Heart Failure Long-Term Registry. Eur Heart J. 2018;39(48):4277–84. https://doi.org/10.1093/eurheartj/ehy626.

  34. Verma A, Kalman JM, Callans DJ. Treatment of patients with atrial fibrillation and heart failure with reduced ejection fraction. Circulation. 2017;135:1547–63.

    Article  CAS  PubMed  Google Scholar 

  35. Aune D, Sen A, Norat T, Janszky I, Romundstad P, Tonstad S, et al. Body mass index, abdominal fatness, and heart failure incidence and mortality: a systematic review and dose-response meta-analysis of prospective studies. Circulation. 2016;133(7):639–49. https://doi.org/10.1161/CIRCULATIONAHA.115.016801.

  36. Packer M, Kitzman DW. Obesity-related heart failure with a preserved ejection fraction: the mechanistic rationale for combining inhibitors of aldosterone, neprilysin, and sodium-glucose cotransporter-2. JACC Heart Fail. 2018;6:633–9.

    Article  PubMed  Google Scholar 

  37. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413–24.

    Article  CAS  PubMed  Google Scholar 

  38. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995–2008.

    Article  CAS  PubMed  Google Scholar 

  39. Petrie MC, Verma S, Docherty KF, Inzucchi SE, Anand I, Belohlávek J, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes. JAMA. 2020;323:1353–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bhatt DL, Szarek M, Steg PG et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2020.

  41. Radholm K, Figtree G, Perkovic V, et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program. Circulation. 2018;138:458–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bhatt DL, Szarek M, Pitt B et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med 2020.

  43. Zannad F, Ferreira JP, Pocock SJ, Zeller C, Anker SD, Butler J et al. Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights From EMPEROR-Reduced. Circulation. 2021;143(4):310–21. https://doi.org/10.1161/CIRCULATIONAHA.120.051685.

  44. Jhund PS, Solomon SD, Docherty KF et al. Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF. Circulation 2020.

  45. Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, 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;396:819–29.

    Article  PubMed  Google Scholar 

  46. Kristensen SL, Docherty KF, Jhund PS, Bengtsson O, Demets DL, Inzucchi SE, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, McMurray JJV Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF. Eur Heart J 2020;41.

  47. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.

    Article  PubMed  Google Scholar 

  48. Kristensen SL, Preiss D, Jhund PS, Squire I, Cardoso JS, Merkely B, Martinez F, Starling RC, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray J, Packer M, PARADIGM-HF Investigators and Committees Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial. Circ Heart Fail 2016;9.

  49. Seferovic JP, Claggett B, Seidelmann SB, Seely EW, Packer M, Zile MR, et al. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial. Lancet Diabetes Endocrinol. 2017;5:333–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Damman K, Gori M, Claggett B, Jhund PS, Senni M, Lefkowitz MP, et al. Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure. JACC Heart Fail. 2018;6:489–98.

    Article  PubMed  Google Scholar 

  51. Velazquez EJ, Morrow DA, DeVore AD, et al. Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380:539–48.

    Article  CAS  PubMed  Google Scholar 

  52. Voors AA, Gori M, Liu LC, et al. Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction. Eur J Heart Fail. 2015;17:510–7.

    Article  CAS  PubMed  Google Scholar 

  53. Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609–20.

    Article  CAS  PubMed  Google Scholar 

  54. Desai AS, Vardeny O, Claggett B, McMurray JJV, Packer M, Swedberg K, et al. Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril: a secondary analysis of the PARADIGM-HF Trial. JAMA Cardiol. 2017;2:79–85.

    Article  PubMed  Google Scholar 

  55. Ferreira JP, Mogensen UM, Jhund PS, Desai AS, Rouleau JL, Zile MR, et al. Serum potassium in the PARADIGM-HF trial. Eur J Heart Fail. 2020;22:2056–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Writing C, Maddox TM, Januzzi JL, Jr. et al. 2021 Update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment: answers to 10 pivotal issues about heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2021.

  57. Ambrosy AP, Braunwald E, Morrow DA, DeVore A, McCague K, Meng X, et al. Angiotensin receptor-neprilysin inhibition based on history of heart failure and use of renin-angiotensin system antagonists. J Am Coll Cardiol. 2020;76:1034–48.

    Article  CAS  PubMed  Google Scholar 

  58. De Vecchis R, Paccone A, Di Maio M. Favorable effects of sacubitril/valsartan on the peak atrial longitudinal strain in patients with chronic heart failure and a history of one or more episodes of atrial fibrillation: a retrospective cohort study. J Clin Med Res. 2020;12:100–7.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Croteau D, Qin F, Chambers JM, Kallick E, Luptak I, Panagia M, et al. Differential effects of sacubitril/valsartan on diastolic function in mice with obesity-related metabolic heart disease. JACC Basic Transl Sci. 2020;5:916–27.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

    Article  CAS  PubMed  Google Scholar 

  61. Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364:11–21.

    Article  CAS  PubMed  Google Scholar 

  62. Preiss D, van Veldhuisen DJ, Sattar N, Krum H, Swedberg K, Shi H, et al. Eplerenone and new-onset diabetes in patients with mild heart failure: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail. 2012;14:909–15.

    Article  CAS  PubMed  Google Scholar 

  63. Yamaji M, Tsutamoto T, Kawahara C, Nishiyama K, Yamamoto T, Fujii M, et al. Effect of eplerenone versus spironolactone on cortisol and hemoglobin A(1)(c) levels in patients with chronic heart failure. Am Heart J. 2010;160:915–21.

    Article  CAS  PubMed  Google Scholar 

  64. Korol S, White M, O'Meara E, et al. Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure? Eur J Clin Pharmacol. 2019;75:837–47.

    Article  CAS  PubMed  Google Scholar 

  65. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry. J Am Coll Cardiol. 2018;72:351–66.

    Article  PubMed  Google Scholar 

  66. Vardeny O, Wu DH, Desai A, Rossignol P, Zannad F, Pitt B, et al. Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure: insights from RALES (Randomized Aldactone Evaluation Study). J Am Coll Cardiol. 2012;60(20):2082–9. https://doi.org/10.1016/j.jacc.2012.07.048.

  67. Beldhuis IE, Myhre PL, Claggett B, Damman K, Fang JC, Lewis EF, et al. Efficacy and safety of spironolactone in patients with HFpEF and chronic kidney disease. JACC Heart Fail. 2019;7:25–32.

    Article  PubMed  Google Scholar 

  68. Rossignol P, Dobre D, McMurray JJ, Swedberg K, Krum H, van Veldhuisen D, et al. Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circ Heart Fail. 2014;7:51–8.

    Article  CAS  PubMed  Google Scholar 

  69. Rossignol P, Cleland JG, Bhandari S, et al. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Circulation. 2012;125:271–9.

    Article  CAS  PubMed  Google Scholar 

  70. Inampudi C, Parvataneni S, Morgan CJ, Deedwania P, Fonarow GC, Sanders PW, et al. Spironolactone use and higher hospital readmission for Medicare beneficiaries with heart failure, left ventricular ejection fraction <45%, and estimated glomerular filtration rate <45 ml/min/1.73 m(2.). Am J Cardiol. 2014;114:79–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Eschalier R, McMurray JJ, Swedberg K, van Veldhuisen D, Krum H, Pocock SJ, et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol. 2013;62:1585–93.

    Article  CAS  PubMed  Google Scholar 

  72. Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen D, Shi H, et al. Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. J Am Coll Cardiol. 2012;59:1598–603.

    Article  CAS  PubMed  Google Scholar 

  73. Cikes M, Claggett B, Shah AM, Desai AS, Lewis EF, Shah SJ, et al. Atrial fibrillation in heart failure with preserved ejection fraction: the TOPCAT Trial. JACC Heart Fail. 2018;6:689–97.

    Article  PubMed  Google Scholar 

  74. Tsujimoto T, Kajio H. Abdominal obesity is associated with an increased risk of all-cause mortality in patients with HFpEF. J Am Coll Cardiol. 2017;70:2739–49.

    Article  PubMed  Google Scholar 

  75. Olivier A, Pitt B, Girerd N, Lamiral Z, Machu JL, McMurray JJV, et al. Effect of eplerenone in patients with heart failure and reduced ejection fraction: potential effect modification by abdominal obesity. Insight from the EMPHASIS-HF trial. Eur J Heart Fail. 2017;19:1186–97.

    Article  CAS  PubMed  Google Scholar 

  76. Packer M. Obesity-associated heart failure as a theoretical target for treatment with mineralocorticoid receptor antagonists. JAMA Cardiol. 2018;3:883–7.

    Article  PubMed  Google Scholar 

  77. Hawkins NM, Petrie MC, Jhund PS, Chalmers GW, Dunn FG, McMurray JJ. Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail. 2009;11:130–9.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Hawkins NM, Petrie MC, Macdonald MR, et al. Heart failure and chronic obstructive pulmonary disease the quandary of beta-blockers and beta-agonists. J Am Coll Cardiol. 2011;57:2127–38.

    Article  CAS  PubMed  Google Scholar 

  79. Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005:CD003566.

  80. Salpeter SR, Ormiston TM, Salpeter EE, Poole PJ, Cates CJ. Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis. Respir Med. 2003;97:1094–101.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  82. Jabbour A, Macdonald PS, Keogh AM, Kotlyar E, Mellemkjaer S, Coleman CF, et al. Differences between beta-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial. J Am Coll Cardiol. 2010;55:1780–7.

    Article  PubMed  Google Scholar 

  83. Stefan MS, Rothberg MB, Priya A, Pekow PS, Au DH, Lindenauer PK. Association between beta-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension. Thorax. 2012;67:977–84.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Mentz RJ, Wojdyla D, Fiuzat M, Chiswell K, Fonarow GC, O'Connor CM. Association of beta-blocker use and selectivity with outcomes in patients with heart failure and chronic obstructive pulmonary disease (from OPTIMIZE-HF). Am J Cardiol. 2013;111:582–7.

    Article  CAS  PubMed  Google Scholar 

  85. Sin DD, McAlister FA. The effects of beta-blockers on morbidity and mortality in a population-based cohort of 11,942 elderly patients with heart failure. Am J Med. 2002;113:650–6.

    Article  CAS  PubMed  Google Scholar 

  86. Haas SJ, Vos T, Gilbert RE, Krum H. Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials. Am Heart J. 2003;146:848–53.

    Article  CAS  PubMed  Google Scholar 

  87. Bobbio M, Ferrua S, Opasich C, Porcu M, Lucci D, Scherillo M, et al. Survival and hospitalization in heart failure patients with or without diabetes treated with beta-blockers. J Card Fail. 2003;9:192–202.

    Article  CAS  PubMed  Google Scholar 

  88. Deedwania PC, Giles TD, Klibaner M, Ghali JK, Herlitz J, Hildebrandt P, et al. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Am Heart J. 2005;149:159–67.

    Article  CAS  PubMed  Google Scholar 

  89. Garcia-Egido A, Andrey JL, Puerto JL, Aranda RM, Pedrosa MJ, López-Sáez JB, et al. Beta-blocker therapy and prognosis of heart failure patients with new-onset diabetes mellitus. Int J Clin Pract. 2015;69:550–9.

    Article  CAS  PubMed  Google Scholar 

  90. Kotecha D, Flather MD, Altman DG, Holmes J, Rosano G, Wikstrand J, et al. Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure. J Am Coll Cardiol. 2017;69:2885–96.

    Article  CAS  PubMed  Google Scholar 

  91. Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JGF, et al. Efficacy of beta blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014;384:2235–43.

    Article  CAS  PubMed  Google Scholar 

  92. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64:e1–76.

    Article  PubMed  Google Scholar 

  93. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey de Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Duke University School of Medicine, Durham, NC, USA

    Christine Chow

  2. Division of Cardiology, Duke University School of Medicine, Durham, NC, USA

    Robert J. Mentz & Stephen J. Greene

  3. Duke Clinical Research Institute, 200 Morris Street, Durham, NC, 27701, USA

    Robert J. Mentz & Stephen J. Greene

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Correspondence to Stephen J. Greene.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

Dr. Chow reports no disclosures. Dr. Mentz receives research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Medtronic, Merck, Novartis, Relypsa, Respicardia, Roche, Sanofi, Vifor, and Windtree Therapeutics. Dr. Greene receives research support from the American Heart Association, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis; serves on advisory boards for Amgen, AstraZeneca, and Cytokinetics; and serves as a consultant for Amgen and Merck.

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This article is part of the Topical Collection on Comorbidities of Heart Failure

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Chow, C., Mentz, R.J. & Greene, S.J. Update on the Impact of Comorbidities on the Efficacy and Safety of Heart Failure Medications. Curr Heart Fail Rep 18, 132–143 (2021). https://doi.org/10.1007/s11897-021-00512-3

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