Chronic stable angina treatment beta blockers

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Associate Editor(s)-In-Chief: ; John Fani Srour, M.D.; Jinhui Wu, M.D.; Lakshmi Gopalakrishnan, M.B.B.S.

Overview
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. B

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.

Indications

 * 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.

Contra-indications

 * 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

Dosage

 * 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.

Drug interaction

 * 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.

Adverse effects

 * 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
 * Bronchospasm
 * 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.

==ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT)  == {{cquote|

Class I
1. It is beneficial to start and continue beta-blocker therapy indefinitely in all patients who have had MI, acute coronary syndrome, or left ventricular dysfunction with or without heart failure symptoms, unless contraindicated. (Level of Evidence: A)

2. Beta-blockers as initial therapy in the absence of contraindications in patients without prior MI. (Level of Evidence: B)}}

==ESC Guidelines- Pharmacological therapy to improve symptoms and/or reduce ischaemia in patients with stable angina (DO NOT EDIT) == {{cquote|

Class I
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)

Class IIa
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)}}

==ESC Guidelines- Pharmacological therapy to improve prognosis in patients with stable angina (DO NOT EDIT) == {{cquote|

Class I
1. Oral beta-blocker therapy in patients post-MI or with heart failure. (Level of Evidence: A)}}

Vote on and Suggest Revisions to the Current Guidelines

 * The Chronic Stable Angina Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines

Guidelines Resources

 * The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina


 * The ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina


 * The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina


 * Guidelines on the management of stable angina pectoris: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology