Chronic stable angina treatment beta blockers
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. ; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. ; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.; Aysha Anwar, M.B.B.S
In patients with stable angina, beta blockers are used as a first line of therapy for both, symptomatic relief and the prevention of ischemic events. The physiologic mechanism of benefit of this therapy is a marked reduction in myocardial oxygen consumption by reducing the heart rate and myocardial contractility. Selective beta-1 blockers are preferred to non-selective beta-blockers due to fewer associated side effects. The most commonly used selective beta-1 blockers are metoprolol, atenolol, and bisoprolol.
Mechanisms of Benefit
- Beta blockers decrease heart rate, blood pressure, and myocardial contractility and, as a result, reduce myocardial oxygen consumption.
- A slowing of heart rate is associated with an increased left ventricular perfusion time. This prolonged diastole helps to improve perfusion to ischemic areas.
- Beta-blocker administration causes a reversal coronary steal phenomenon that results in shunting of blood from the non-ischemic to ischemic zones as a consequence of increased vascular resistance, thereby improving perfusion to ischemic areas.
- Beta-blockers curve the effects of exercise such as increase in heart rate and blood pressure. In patients with stable angina, beta adrenergic blocking agents increase exercise tolerance, reduce the time to the onset of angina and ST segment depression and also reduce short-acting nitrate consumption. Despite this, the double product threshold (heart rate multiplied by blood pressure) at which ischemia occurs remains unchanged.
- It is beneficial to start and continue beta blocker drug therapy indefinitely in all patients who have had myocardial infarction, acute coronary syndrome (ACS) or left ventricular dysfunction with or without heart failure symptoms, unless contraindicated.
- Beta blocking agents with beta selectivity (such as metoprolol and atenolol) are preferable in patients with mild asthma, chronic obstructive pulmonary disease (COPD), insulin dependent diabetes (IDDM) or intermittent claudication. However, with increased doses of beta blockers, selectivity is lost and both types of beta receptors are blocked.
- In patients with heart failure, selective beta-1 blockers, such as metoprolol or bisoprolol, have been shown to effectively reduce cardiac events and prolong survival. Non selective beta blockers such as carvedilol has also shown to reduce mortality in patients with heart failure.
- Avoid beta-blockers with intrinsic sympathomimetic activity as they provide less benefit in the reduction of post-MI mortality.
- Beta-blockers that induce symptomatic heart failure should either be discontinued or have the dose reduced.
- Severe bradycardia
- Episodes of second or third degree AV blocks.
- Severe peripheral vascular disease
- The effective dose of any beta blocker drug varies considerably from patient to patient.
- For an effective treatment, resting heart rate should be reduced to between 45 and 60 bpm (beats per minute) and heart rate should be below 90 beats per minute during moderate exercise, such as climbing two stairs at a normal pace.
- For maintenance therapy of stable angina, beta blocking drugs with a relatively long half-life are preferable.
- Beta blockers when used concomitantly with diuretics, may increase the blood sugar level and reduce insulin sensitivity.
- In patients with insulin dependent diabetes mellitus (IDDM), beta-blockers may mask hypoglycemic symptoms.
- In patients with vasospastic angina, beta-blocker therapy may precipitate symptoms.
- The sudden withdrawal of beta blocker therapy may result in worsening of angina (rebound effect) and precipitation of acute ischemic episodes. Hence, it is preferable to taper these medications gradually over 2 to 3 weeks.
- Major side effects of beta blocker therapy include:
- Symptomatic bradycardia
- Worsening claudication
- Impaired exercise capacity
- Insomnia, nightmares
- Fatigue and sexual dysfunction
- Beta blocker induced changes in lipid profile such as an increase in triglycerides and reduction in high density lipoprotein (HDL-C) have not yet been defined.
Supportive Trial Data
- Reviews of 150 randomized trials related to the management of myocardial infarction suggest that beta-blockers reduce the risk of cardiovascular mortality by approximately 30%.
- In a recent meta-analysis that assessed the benefits of beta-blocker therapy on mortality, researchers observed no significant benefits with acute therapy. Long-term therapy, however, reported a significant 24% relative risk reduction in mortality after MI.
- The APSIS trial, a randomized, double-blind, double dummy trial of 809 patients with clinically diagnosed stable angina pectoria, compared the administration of either, metoprolol or verapamil and its influence on combined cardiovascular endpoints. Researchers reported that the combined endpoints (30.8% in patients treated with metaprolol and 29.3% in patients treated with verapamil) and non-fatal events including acute MI, unstable angina, cerebrovascular or peripheral vascular events (26.1% in patients treated with metaprolol and 24.3% in patients treated with verapamil) during a median follow-up of 3.4 years (range 6 and 75 months) did not differ between the two group. It was therefore concluded that both drugs were well tolerated and had equivalent influence on mortality, cardiovascular endpoints and meaures of quality of life.
- A registry based extended follow-up (median of 9.1 years) of patients who participated in the APSIS study, reported no change in the mortality and non-fatal MI results among the two groups. This study also reported female patients without diabetes to have an excellent prognosis.
- The TIBET trial, a randomized, double-blind, parallel trial of 682 patients (male and female) with exercise-induced chronic stable angina who were not being considered for surgery, assessed the administration of either atenolol, nifedipine or their combination on Holter monitoring efficacy and hard and hard+soft endpoint. Researchers reported that the combined cardiovascular and non-fatal end points during a median follow-up of 2 years did not differ significantly between the two group, but combination of the two drugs was reported to be advantageous.
2012 Chronic Angina Guidelines Update for the Management of Patients With Chronic Stable Angina (DO NOT EDIT)
Beta Blockers (DO NOT EDIT)
|"1. Beta blockers should be prescribed as initial therapy for relief of symptoms in patients with SIHD (Level of Evidence: B) "|
2006 ESC Guidelines on the Management of Stable Angina Pectoris (DO NOT EDIT)
Beta Blockers (DO NOT EDIT)
|"1. Test the effects of a beta-1 blocker, and titrate to full dose; consider the need for 24 h protection against ischemia. (Level of Evidence: A) "|
|"2. In case of beta-blocker intolerance or poor efﬁcacy attempt monotherapy with a CCB (Level of Evidence: A), long-acting nitrate (Level of Evidence: C), or nicorandil. (Level of Evidence: C) "|
|"3. If the effects of beta-blocker monotherapy are insufﬁcient, add a dihydropyridine CCB. (Level of Evidence: B) "|
|"4. Oral beta-blocker therapy in patients post-MI or with heart failure. (Level of Evidence: A) "|
|"1. In case of beta-blocker intolerance try sinus node inhibitor. (Level of Evidence: B) "|
|"2. If CCB monotherapy or combination therapy (CCB with beta-blocker) is unsuccessful, substitute the CCB with a long-acting nitrate or nicorandil. Be careful to avoid nitrate tolerance. (Level of Evidence: C) "|
- ↑ Pepine CJ, Cohn PF, Deedwania PC, Gibson RS, Handberg E, Hill JA et al. (1994) Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST) Circulation 90 (2):762-8. PMID: 8044945
- ↑ 2.0 2.1 2.2 Savonitto S, Ardissino D (1998) Selection of drug therapy in stable angina pectoris. Cardiovasc Drugs Ther 12 (2):197-210. PMID: 9652879
- ↑ 3.0 3.1 3.2 Thadani U (1999) Treatment of stable angina. Curr Opin Cardiol 14 (4):349-58. PMID: 10448616
- ↑ (1981) Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 304 (14):801-7. DOI:10.1056/NEJM198104023041401 PMID: 7010157
- ↑ Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999) ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). Circulation 99 (21):2829-48.  PMID: 10351980
- ↑ Kaufmann PA, Mandinov L, Seiler C, Hess OM (2000) Impact of exercise-induced coronary vasomotion on anti-ischemic therapy. Coron Artery Dis 11 (4):363-9. PMID: 10860181
- ↑ (1999) Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) Lancet 353 (9169):2001-7. PMID: 10376614
- ↑ (1999) The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 353 (9146):9-13. PMID: 10023943
- ↑ Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM et al. (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 334 (21):1349-55. DOI:10.1056/NEJM199605233342101 PMID: 8614419
- ↑ 10.0 10.1 Freemantle N, Urdahl H, Eastaugh J, Hobbs FD (2002) What is the place of beta-blockade in patients who have experienced a myocardial infarction with preserved left ventricular function? Evidence and (mis)interpretation. Prog Cardiovasc Dis 44 (4):243-50. PMID: 12007080
- ↑ Ko DT, Hebert PR, Coffey CS, Sedrakyan A, Curtis JP, Krumholz HM (2002) Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA 288 (3):351-7. PMID: 12117400
- ↑ Yusuf S, Wittes J, Friedman L (1988) Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. JAMA 260 (14):2088-93. PMID: 2901501
- ↑ Rehnqvist N, Hjemdahl P, Billing E, Björkander I, Eriksson SV, Forslund L et al. (1996) Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS) Eur Heart J 17 (1):76-81. PMID: 8682134
- ↑ Hjemdahl P, Eriksson SV, Held C, Forslund L, Näsman P, Rehnqvist N (2006) Favourable long term prognosis in stable angina pectoris: an extended follow up of the angina prognosis study in Stockholm (APSIS). Heart 92 (2):177-82. DOI:10.1136/hrt.2004.057703 PMID: 15951393
- ↑ Dargie HJ, Ford I, Fox KM (1996) Total Ischaemic Burden European Trial (TIBET). Effects of ischaemia and treatment with atenolol, nifedipine SR and their combination on outcome in patients with chronic stable angina. The TIBET Study Group. Eur Heart J 17 (1):104-12. PMID: 8682116
- ↑ 16.0 16.1 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP; et al. (2012). "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. 126 (25): 3097–137. doi:10.1161/CIR.0b013e3182776f83. PMID 23166210.
- ↑ 17.0 17.1 Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 116 (23):2762-72. PMID: 17998462
- ↑ Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation 107 (1):149-58. PMID: 12515758
- ↑ 19.0 19.1 Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F; et al. (2006). "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. 27 (11): 1341–81. doi:10.1093/eurheartj/ehl001. PMID 16735367.