Pharmacological Management

Beta Blockers

Following myocardial infarction (MI), long-term treatment with a beta-blocker has been shown to be effective in reducing morbidity and mortality^.1,2 There is most evidence to support the use of propranolol, timolol and metoprolol,² but carvedilol has been shown, in a prospective, placebo-controlled trial, to reduce the risk of death and recurrent non-fatal MI in patients with left ventricular dysfunction following an MI.³

Rationale

Beta-blockers are beneficial following MI because they oppose the effects of the sympathetic nervous system (SNS), which include:

• increased heart rate 
• peripheral vasoconstriction 
• activation of the renin-angiotensin-aldosterone system (RAAS).

SNS activation is a key compensatory mechanism when cardiac output falls as a result of left ventricular dysfunction (see Pathophysiology). Although the effects of the SNS are initially helpful in improving haemodynamic stability, they increase myocardial workload and oxygen demand, placing greater strain on the heart and precipitating or worsening heart failure.

Recently, the benefits of beta-blockers in the post-MI setting have been found to be proportional to the reduction in heart rate. In one meta-regression study, each reduction in resting heart rate of 10 beats per minute was associated with a 30% reduction in the risk of cardiac death.⁴

Evidence

Evidence to support beta-blockers in post-MI care comes from numerous small- to medium-sized studies carried out mainly during the pre-reperfusion era.^1,2 In trials lasting 6 months or longer, beta-blocker therapy was associated with a 23% reduction in the risk of death compared with control.²

Treating 107 MI survivors with a beta-blocker for one year has been estimated to prevent one non-fatal reinfarction, and treating 84 patients for one year will avoid one death.²

In the CAPRICORN* trial,³ carvedilol, which blocks both beta- and alpha1-adrenoceptors, reduced all-cause mortality by 23% compared with placebo in patients with left ventricular dysfunction (left ventricular ejection fraction ≤40%) following MI.

Guidelines

Recommendations for the use of beta-blockers post-MI vary slightly according to diagnosis. European Society of Cardiology (ESC) guidelines state that beta?blockers should be initiated in all patients with non-ST-segment elevation MI (NSTEMI) (unless there are contraindications), and continued indefinitely in patients with left ventricular dysfunction.⁵ Symptoms of heart failure do not need to be present.⁵ In contrast, beta-blockers are indicated for indefinite use in all patients with ST?segment elevation MI (STEMI) [unless contraindicated], regardless of left ventricular functional status.¹

Choice of beta-blocker

There is good evidence to support the long-term use of propranolol, timolol and metoprolol following MI,² and to support the use of carvedilol in patients with MI and left ventricular dysfunction.³ Beta-blockers with intrinsic sympathomimetic activity (e.g. pindolol and practolol) should be avoided because they may be associated with less benefit than other drugs in the class.² Additionally, there is insufficient evidence to support the long-term use of atenolol in the post-MI setting, despite its widespread use.²

* CAPRICORN = Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction