Beta blockers in the management of stable angina pectoris
- Joseph P Kannam, MD
Joseph P Kannam, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Julian M Aroesty, MD
Julian M Aroesty, MD
- Clinical Associate Professor of Medicine
- Harvard Medical School
- Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
- Editor-in-Chief — Cardiovascular Medicine
- Section Editor — Coronary Heart Disease
- Section Editor — Myopericardial Disease
- Professor of Medicine
- Mayo Medical School
Beta blockers are first-line therapy in the control of symptoms in patients with chronic stable angina, particularly effort-induced angina. They are recommended for use in such patients in guidelines from the American College of Cardiology Foundation/American Heart Association/American College of Physicians/American Association for Thoracic Surgery/Preventive Cardiovascular Nurses Association/Society for Cardiovascular Angiography and Interventions/Society of Thoracic Surgeons (ACCF/AHA/ACP/AATS/PCNA/SCAI/STS) and from the European Society of Cardiology [1-4].
The major issues regarding the use of beta blockers in the medical management of the patient with stable angina and the evidence that these drugs are effective will be reviewed here. Their role, compared with other drugs, in the overall management of angina is discussed separately. (See "Stable ischemic heart disease: Overview of care".)
MECHANISM OF ACTION
The physiologic effects of catecholamines (norepinephrine and epinephrine) are mediated by activation of specific alpha and beta adrenergic receptors. There are at least three distinct types of beta receptors [5-7]:
●Beta-1, which are found primarily in heart muscle. Activation of these receptors results in increases in heart rate, contractility, and atrioventricular (AV) conduction, and a decrease in AV node refractoriness.
●Beta-2, which are present in heart muscle but are more prominent in bronchial and peripheral vascular smooth muscle. Activation of these receptors results in vasodilatation and bronchodilatation.
- Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006; 27:1341.
- Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:e354.
- Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:3097.
- Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014; 64:1929.
- Lands AM, Arnold A, McAuliff JP, et al. Differentiation of receptor systems activated by sympathomimetic amines. Nature 1967; 214:597.
- Gauthier C, Tavernier G, Charpentier F, et al. Functional beta3-adrenoceptor in the human heart. J Clin Invest 1996; 98:556.
- Krief S, Lönnqvist F, Raimbault S, et al. Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest 1993; 91:344.
- Lefkowitz RJ, Caron MG, Stiles GL. Mechanisms of membrane-receptor regulation. Biochemical, physiological, and clinical insights derived from studies of the adrenergic receptors. N Engl J Med 1984; 310:1570.
- Frishman WH. Beta-adrenergic blocker withdrawal. Am J Cardiol 1987; 59:26F.
- Psaty BM, Koepsell TD, Wagner EH, et al. The relative risk of incident coronary heart disease associated with recently stopping the use of beta-blockers. JAMA 1990; 263:1653.
- LeWinter MM, Crawford MH, Karliner JS, ORourke RA. Effects of oral propranolol in normal subjects. Clin Pharmacol Ther 1975; 17:709.
- Nayler WG, Carson V. Effect of stellate ganglion stimulation on myocardial blood flow, oxygen consumption, and cardiac efficiency during beta-adrenoceptor blockade. Cardiovasc Res 1973; 7:22.
- Opie LH. Drugs and the heart. Lancet 1980; 1:693.
- Frishman W. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 1. Pharmacodynamic and pharmacokinetic properties. Am Heart J 1979; 97:663.
- Frishman WH, Lazar EJ, Gorodokin G. Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents. Clin Pharmacokinet 1991; 20:311.
- Lertora JJ, Mark AL, Johannsen J, et al. Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon. J Clin Invest 1975; 56:719.
- Magder S, Sami M, Ripley R, Lisbona R. Comparison of the effects of pindolol and propranolol on exercise performance in patients with angina pectoris. Am J Cardiol 1987; 59:1289.
- Wassertheil-Smoller S, Oberman A, Blaufox MD, et al. The Trial of Antihypertensive Interventions and Management (TAIM) Study. Final results with regard to blood pressure, cardiovascular risk, and quality of life. Am J Hypertens 1992; 5:37.
- Warren SG, Brewer DL, Orgain ES. Long-term propranolol therapy for angina pectoris. Am J Cardiol 1976; 37:420.
- Alderman EL, Davies RO, Crowley JJ, et al. Dose response effectiveness of propranolol for the treatment of angina pectoris. Circulation 1975; 51:964.
- Furberg B, Dahlqvist A, Raak A, Wrege U. Comparison of the new beta-adrenoceptor antagonist, nadolol, and propranolol in the treatment of angina pectoris. Curr Med Res Opin 1978; 5:388.
- Jackson G, Harry JD, Robinson C, et al. Comparison of atenolol with propranolol in the treatment of angina pectoris with special reference to once daily administration of atenolol. Br Heart J 1978; 40:998.
- Borer JS, Comerford MB, Sowton E. Assessment of metoprolol, a cardioselective beta-blocking agent, during chronic therapy in patients with angina pectoris. J Int Med Res 1976; 4:15.
- Savonitto S, Ardissiono D, Egstrup K, et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study. J Am Coll Cardiol 1996; 27:311.
- Jackson G, Schwartz J, Kates RE, et al. Atenolol: once-daily cardioselective beta blockade for angina pectoris. Circulation 1980; 61:555.
- Kostis JB, Frishman W, Hosler MH, et al. Treatment of angina pectoris with pindolol: the significance of intrinsic sympathomimetic activity of beta blockers. Am Heart J 1982; 104:496.
- Weiss R, Ferry D, Pickering E, et al. Effectiveness of three different doses of carvedilol for exertional angina. Carvedilol-Angina Study Group. Am J Cardiol 1998; 82:927.
- Hauf-Zachariou U, Blackwood RA, Gunawardena KA, et al. Carvedilol versus verapamil in chronic stable angina: a multicentre trial. Eur J Clin Pharmacol 1997; 52:95.
- Quyyumi AA, Wright C, Mockus L, et al. Effects of combined alpha and beta adrenoceptor blockade in patients with angina pectoris. A double blind study comparing labetalol with placebo. Br Heart J 1985; 53:47.
- MECHANISM OF ACTION
- Upregulation of beta receptors
- Cardiovascular effects of beta blockers
- PHARMACOLOGIC CHARACTERISTICS
- Intrinsic sympathomimetic activity
- Alpha-adrenergic blocking activity
- ADVERSE EFFECTS OF BETA BLOCKERS
- EFFICACY OF BETA BLOCKERS IN STABLE ANGINA
- Nonselective agents
- Cardioselective drugs
- Agents with intrinsic sympathomimetic activity
- Agents with alpha blocking activity
- THERAPEUTIC GOALS
- CHOOSING AN AGENT
- Patients with heart failure due to systolic dysfunction
- SUMMARY AND RECOMMENDATIONS