Clinical dilemmas: beta-adrenoblockers in atherosclerosis
Beta-blockers are the cornerstone of treatment for various cardiovascular conditions. Beta-blockers were discovered as antianginal drugs in the 1960s and are currently widely used in heart failure, arrhythmias, and ischemic heart disease. In this article, we review the evidence for the beneficial effects of beta-blockers in these conditions, as well as the current recommendations in clinical practice guidelines for their use. Surprisingly, despite having been prescribed for more than 4 decades, new, previously unnoticed mechanisms of action on cellular compartments are still being discovered, which continues to open up new horizons for their use. All in all, beta-blockers are one of the most fascinating drug groups in our therapeutic armamentarium.
Lewington, S., Clarke, R., Quizibash, N., et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 studies. Lancet 2002;360:1903-1913.
Williams, B., Poulter, N.R., Brown, M.J., et al., British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ, 2004; 328(7440): p. 634-640. 27.
Roger, V., Go, A., Lloyd-Jones, D., et al. Heart disease and stroke statistics – 2012 update: A report from American Heart Association. Circulation 2012; 125: e2-e220.
Alexander, R. Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995; 25:155-161.
Dorobantu, M., Tatu, O. Hipertensiunea arteriala esentiala. In: Apetrei, E. ed. Cardiologie clinica. Bucuresti: Editura Medicala Callisto; 2015. P. 627-652.
Forouzanfar, MH, Liu, P, Roth, GA, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015. JAMA 2017; 317:165–182.
Ettehad, D., Emdin, C.A, Kiran, A., Anderson, S.G. et all. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387:957–967.
Brunstrom, M, Carlberg, B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Intern Med 2018; 178:28–36.
C.S. Wiysonge, H.A. Bradley, J. Volmink, B.M. Mayosi, L.H. Opie. Beta-blockers for hypertension. Cochrane Database Syst Rev., (2017),
B. Carlberg, O. Samuelsson, L.H. Lindholm. Atenolol in hypertension: is it a wise choice? Lancet., 364 (2004), pp. 1684-1689.
L.M. Kuyper, N.A. Khan. Atenolol vs nonatenolol beta-blockers for the treatment of hypertension: a meta-analysis. Can J Cardiol., 30 (2014), pp. S47-S53.
Quirke V. Putting Theory into Practice: James Black. Receptor Theory and the Development of the beta-blockers at ISI 1958-1978. Medical History 2006;50:69-92.
Baker JG, Hill SJ, Summers RJ. Evolution of β – blockers; from anti-anginal drugs to ligand – directed signaling. Trends Pharmacol Sci. 2011;32:227-234.
Baker JG. The selectivity of beta-adrenoreceptor agonist at human beta1-, beta2and beta3-adrenoreceptors. Br J Pharmacol. 2010;160:1048-1061.
Manoach M., Tribulova N. Sotalol: the mechanism of its antiarrhythmic-defibrillating effect. Cardiovasc Drug Rev. 2001;19:172-182.
Dulin B., Abraham WT. Pharmacology of carvedilol. Am J Cardiol. 2004;93(9A):3B-6B.
Riva E., Mennini T., Latini R. the alfaand beta-adrenoreceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers. Br J Pharmacol. 1991;104:823-828.
Frazier Ep., Michel-Reher MB., Van Loenen p., et al. Lack of evidence that nebivolol is a β3 – adrenoreceptor agonist. Eur J Pharmacol. 2011;654:86-91.
Gupta S., Wright HM. Nebivolol: a highly selective beta1-adrenergic receptor blocker that cause vasodilation by increasing nitric oxide. Cardiovasc Ther. 2008;26:189-202.
Brodde OE. β-adrenoreceptor blocker treatment and the cardiac β-adrenoreceptor-G-proteins – adenylyl cyclase system in chronic heart failure. Naunyn-Schmiedebergs Arch Pharmacol. 2007:374:361-372.
Okin P.M., Hille D.A.Kjeldsen S.E., et all. Impact of lower achieved blood pressure on outcomes in hypertensive patients. J Hypertens 2012;30:802-810.
Bangalore S., Qin J., Sloan S., et all. For the PROVE IT-TIMI. What is the optimal blood pressure in patients after acute coronary syndromes? Relationship of blood pressure and cardiovascular events in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Trombolysis in Myocardial Infarction (PROVE IT-TIMI 22 Trial). Ciculation 2010;122:2142-2151.
Mancia G., Messerli F., Bakris G., et al. Blood pressure control and improved cardiovascular outcomes in the International Verapamyl SR-Trandolapril Study. Hypertension 2007;50:299-305.
Mancia G., Fagard R., Narkiewicz K., et a. 2013 ESH/ESC Guidelines for the menagement of arterial hypertension. Eur heart J 2013;34:2159-2219.
The Task Force on Beta-Blockers of the European Society of Cardiology. Expert consensus document on beta-adrenergic receptor blockers. European Heart Journal (2004) 25, 1341-1362.
From the National Heart, Lung, and Blood Institute, Bethesda, Md. A randomised trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 1982;247(12):1707-1714. doi:10.1001/ jama.1982.03320370021023.
From the National Heart, Lung, and Blood Institute, Bethesda, Md. A randomised trial of propranolol in patients with acute myocardial infarction. II Morbidity results. JAMA. 1983;250(20):2814-2819. doi:10.1001/ jama.1983.03340200048027.
Pederson T.R. – The Norwegian Multicenter Study of Timolol after Myocardial Infarction. Circulation. 1983;67:149-153.
Dargie H.J. – Effect of Carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomized trial. Lancet. 2001;357(9266):1385-1390.
Sackner-Bernstein J.D. New evidence from the CAPRICORN Trial: the role of carvedilol in high risk, post-myocardial infarction patients. Rev Cardiovasc Med. 2003;4 Suppl 3:S25-9.
Gottlieb S.S., McCarter R.J., Vogel R.A. Effect of beta-blockade on mortality among high-risk and lowrisk patients after myocardial infarction. N Engl J Med. 1998;339:489-49.
ESC/ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) Authors/Task Force Members: Bryan Williams, Giuseppe Mancia, Wilko Spiering, et al. European Heart Journal (2018) 39, 3021–3104.
Zanchetti A., Bond M.G., Hennig M., et al. On behalv of the ELSA investigators. Calcium antagonist lacidipine slows down progression of asymptomatc carotid atherosclerosis. Principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation. 2002;106:2422-2427.
Zanchetti A., Crepaldi G., Bond M.G., et al. On behalv of PHYLLIS Investigators. Different effects of antihypertensive regimens based on fosinopril or hydrochlothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis. Principal results of PHYLLIS randomized double-blind trial. Stroke. 2004;35:2807-2812.
Adler A.I., Stratton I.M., Neil H.A., et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;321:412-419.
Paravastu S.C., Mendonca D.A., da Silva A., et al. Beta-blockers for peripheral arterial disease. Eur J Vasc Endovasc Surg 2009;38:66-70.
Radack K., Deck C. Beta-adrenergic blockers therapy does not worsen intermitentclaudication in subjects with periferal arterial disease. A meta-analysis of randomized controlled trials. Arch Int Med. 1991;151:1769-1776.
Copyright (c) 2023 Bulletin of the Academy of Sciences of Moldova. Medical Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.