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Beta Blockers in Contemporary Cardiology: Is It Better to Cast Them Out?

  • Received : 2023.07.24
  • Accepted : 2024.02.13
  • Published : 2024.04.01

Abstract

Beta blockers are one of the commonest prescription drugs in medicine and they have been thought to revolutionize the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) in the last century. In addition to HFrEF, they are prescribed for a variety of diseases in cardiology from hypertension to HF, angina, and stable coronary artery disease (CAD). The increased prescription of beta blockers in conditions like HF with preserved ejection fraction (HFpEF), and stable CAD may be doing more harm than good as per the data we have so far. The available data shows that beta blockers are associated with increased stroke risk and atrial fibrillation (AF) in hypertension and in patients with HFpEF, they have been associated with decreased exercise capacity. In patients with stable CAD and patients with myocardial infarction with normal systolic functions, beta blockers don't offer any mortality benefit. In this article, we critically review the common indications and the uses of beta blockers in patients with HFpEF, CAD, hypertension and AF and we propose that beta blockers are overprescribed under the shadow of their beneficial effects in patients with HFrEF.

Keywords

References

  1. Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC. A new adrenergic beta-receptor antagonist. Lancet 1964;283:1080-1. https://doi.org/10.1016/S0140-6736(64)91275-9
  2. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9-13. https://doi.org/10.1016/S0140-6736(98)11181-9
  3. Eichhorn EJ, Bristow MR. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Curr Control Trials Cardiovasc Med 2001;2:20-3. https://doi.org/10.1186/cvm-2-1-020
  4. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001-7. https://doi.org/10.1016/S0140-6736(99)04440-2
  5. Solomon SD, McMurray JJ, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019;381:1609-20. https://doi.org/10.1056/NEJMoa1908655
  6. Ferreira JP, Butler J, Zannad F, et al. Mineralocorticoid receptor antagonists and empagliflozin in patients with heart failure and preserved ejection fraction. J Am Coll Cardiol 2022;79:1129-37. https://doi.org/10.1016/j.jacc.2022.01.029
  7. Silverman DN, Plante TB, Infeld M, et al. Association of β-blocker use with heart failure hospitalizations and cardiovascular disease mortality among patients with heart failure with a preserved ejection fraction: a secondary analysis of the TOPCAT trial. JAMA Netw Open 2019;2:e1916598.
  8. Cleland JG, Bunting KV, Flather MD, et al. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. Eur Heart J 2018;39:26-35. https://doi.org/10.1093/eurheartj/ehx564
  9. Palau P, Seller J, Dominguez E, et al. Effect of β-blocker withdrawal on functional capacity in heart failure and preserved ejection fraction. J Am Coll Cardiol 2021;78:2042-56. https://doi.org/10.1016/j.jacc.2021.08.073
  10. Park JJ, Choi HM, Hwang IC, Park JB, Park JH, Cho GY. Myocardial strain for identification of β-blocker responders in heart failure with preserved ejection fraction. J Am Soc Echocardiogr 2019;32:1462-1469.e8. https://doi.org/10.1016/j.echo.2019.06.017
  11. Bangalore S, Makani H, Radford M, et al. Clinical outcomes with β-blockers for myocardial infarction: a meta-analysis of randomized trials. Am J Med 2014;127:939-53. https://doi.org/10.1016/j.amjmed.2014.05.032
  12. Dondo TB, Hall M, West RM, et al. β-blockers and mortality after acute myocardial infarction in patients without heart failure or ventricular dysfunction. J Am Coll Cardiol 2017;69:2710-20. https://doi.org/10.1016/j.jacc.2017.03.578
  13. Bangalore S, Steg G, Deedwania P, et al. β-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 2012;308:1340-9. https://doi.org/10.1001/jama.2012.12559
  14. Ozasa N, Morimoto T, Bao B, et al. β-blocker use in patients after percutaneous coronary interventions: one size fits all? Worse outcomes in patients without myocardial infarction or heart failure. Int J Cardiol 2013;168:774-9. https://doi.org/10.1016/j.ijcard.2012.10.001
  15. Lee SJ, Choi DW, Kim C, et al. Long-term beta-blocker therapy in patients with stable coronary artery disease after percutaneous coronary intervention. Front Cardiovasc Med 2022;9:878003.
  16. Arero AG, Vasheghani-Farahani A, Soltani D. Meta-analysis of the usefulness of beta-blockers to reduce the risk of major adverse cardiovascular events in patients with stable coronary artery disease without prior myocardial infarction or left ventricular dysfunction. Am J Cardiol 2021;158:23-9. https://doi.org/10.1016/j.amjcard.2021.08.005
  17. Godoy LC, Farkouh ME, Austin PC, et al. Association of beta-blocker therapy with cardiovascular outcomes in patients with stable ischemic heart disease. J Am Coll Cardiol 2023;81:2299-311. https://doi.org/10.1016/j.jacc.2023.04.021
  18. Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008;372:817-21. https://doi.org/10.1016/S0140-6736(08)61171-X
  19. Cooney MT, Vartiainen E, Laatikainen T, Juolevi A, Dudina A, Graham IM. Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. Am Heart J 2010;159:612-619.e3. https://doi.org/10.1016/j.ahj.2009.12.029
  20. Park JJ, Kim SH, Kang SH, et al. Differential effect of β-blockers according to heart rate in acute myocardial infarction without heart failure or left ventricular systolic dysfunction: a cohort study. Mayo Clin Proc 2019;94:2476-87. https://doi.org/10.1016/j.mayocp.2019.05.033
  21. Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014;371:1091-9. https://doi.org/10.1056/NEJMoa1406430
  22. Steg PG, Ferrari R, Ford I, et al. Heart rate and use of beta-blockers in stable outpatients with coronary artery disease. PLoS One 2012;7:e36284.
  23. Bangalore S, Parkar S, Grossman E, Messerli FH. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am J Cardiol 2007;100:1254-62. https://doi.org/10.1016/j.amjcard.2007.05.057
  24. Tsujimoto T, Sugiyama T, Shapiro MF, Noda M, Kajio H. Risk of cardiovascular events in patients with diabetes mellitus on β-blockers. Hypertension 2017;70:103-10. https://doi.org/10.1161/HYPERTENSIONAHA.117.09259
  25. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006;113:1213-25. https://doi.org/10.1161/CIRCULATIONAHA.105.595496
  26. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension 2007;50:197-203. https://doi.org/10.1161/HYPERTENSIONAHA.107.089078
  27. Lindholm LH, Carlberg B, Samuelsson O. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005;366:1545-53. https://doi.org/10.1016/S0140-6736(05)67573-3
  28. Thomopoulos C, Bazoukis G, Tsioufis C, Mancia G. Beta-blockers in hypertension: overview and meta-analysis of randomized outcome trials. J Hypertens 2020;38:1669-81. https://doi.org/10.1097/HJH.0000000000002523
  29. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009;338:b1665.
  30. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the task force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021;42:373-498. https://doi.org/10.1093/eurheartj/ehaa612
  31. Chao TF, Liu CJ, Tuan TC, et al. Rate-control treatment and mortality in atrial fibrillation. Circulation 2015;132:1604-12. https://doi.org/10.1161/CIRCULATIONAHA.114.013709
  32. Koldenhof T, Wijtvliet PE, Pluymaekers NA, et al. Rate control drugs differ in the prevention of progression of atrial fibrillation. Europace 2022;24:384-9. https://doi.org/10.1093/europace/euab191
  33. Daoud EG, Knight BP, Weiss R, et al. Effect of verapamil and procainamide on atrial fibrillation-induced electrical remodeling in humans. Circulation 1997;96:1542-50. https://doi.org/10.1161/01.CIR.96.5.1542
  34. de Vos CB, Nieuwlaat R, Crijns HJ, et al. Autonomic trigger patterns and anti-arrhythmic treatment of paroxysmal atrial fibrillation: data from the Euro Heart Survey. Eur Heart J 2008;29:632-9. https://doi.org/10.1093/eurheartj/ehn025
  35. Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712-9. https://doi.org/10.1016/j.jacc.2004.10.068
  36. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906. https://doi.org/10.1016/S0140-6736(05)67185-1
  37. Meyer M, Lustgarten D. Beta-blockers in atrial fibrillation-trying to make sense of unsettling results. Europace 2023;25:260-2. https://doi.org/10.1093/europace/euad010
  38. Ulimoen SR, Enger S, Pripp AH, et al. Calcium channel blockers improve exercise capacity and reduce N-terminal pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation. Eur Heart J 2014;35:517-24. https://doi.org/10.1093/eurheartj/eht429
  39. Tsuneda T, Yamashita T, Fukunami M, et al. Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study. Circ J 2006;70:965-70. https://doi.org/10.1253/circj.70.965