What are the potential side effects of Metoprolol (beta-blocker) in patients with a history of cardiovascular disease, particularly those with heart failure or bronchospastic disease?

Metoprolol Side Effects

Metoprolol causes hypotension, worsening heart failure, bronchospasm, and bradycardia as its primary cardiovascular side effects, with the FDA specifically warning that it can precipitate heart failure, cardiogenic shock, and severe bradycardia including cardiac arrest. 1

Major Cardiovascular Side Effects

Heart Failure Exacerbation

• Metoprolol can depress myocardial contractility and precipitate heart failure or cardiogenic shock, requiring dose reduction or discontinuation if signs of heart failure develop 1
• During titration, monitor closely for worsening heart failure symptoms and fluid retention; if deterioration occurs, first increase diuretics or ACE-inhibitor doses before reducing the beta-blocker 2
• In controlled trials, the absolute annual risk increase for hypotension was 11 per 1000 patients treated 3

Bradycardia and Conduction Abnormalities

• Bradycardia, sinus pause, heart block, and cardiac arrest have occurred with metoprolol use 1
• Patients with first-degree AV block, sinus node dysfunction, or conduction disorders face increased risk 1
• The absolute annual risk increase for bradycardia is 38 per 1000 patients 3
• If heart rate falls below 50 bpm with worsening symptoms, halve the metoprolol dose or stop if severe deterioration occurs 2

Hypotension

• Symptomatic hypotension manifests as dizziness, lightheadedness, or confusion 2
• The absolute annual risk increase for dizziness is 57 per 1000 patients 3
• Manage by first reducing or stopping nitrates, calcium-channel blockers, and other vasodilators; consider reducing diuretics if no signs of congestion exist 2
• Concurrent medications that lower blood pressure increase hypotension risk, particularly with polypharmacy in elderly patients 4

Respiratory Side Effects

Bronchospasm

• Patients with bronchospastic disease should generally not receive beta-blockers, including metoprolol 1
• Despite relative beta-1 selectivity, metoprolol can still precipitate bronchospasm 2, 1
• Non-selective beta-blockers including carvedilol are specifically contraindicated in patients with bronchospasm 5
• If metoprolol must be used in bronchospastic disease patients who cannot tolerate alternatives, use the lowest possible dose and ensure bronchodilators (including beta-2 agonists) are readily available 1
• In overdose situations, bronchospasm should be treated with beta-2-stimulating agents and/or theophylline derivatives 1

Metabolic Side Effects

Diabetes and Hypoglycemia

• Beta-blockers mask tachycardia occurring with hypoglycemia, though other manifestations like dizziness and sweating remain largely unaffected 1, 4
• First- and second-generation beta-blockers are associated with increased incidence of new-onset diabetes 4
• Unfavorable changes in blood lipids have been reported 4

Neurological Side Effects

• Sleep disturbances, including nightmares and night terrors, can occur 4
• Temporary fatigue, dizziness, and headache are among the most frequently reported side effects 6
• Notably, controlled trials showed no significant absolute risk of fatigue (3 per 1000 annually) 3

Critical Warnings for Specific Populations

Patients with Coronary Artery Disease

• Never abruptly discontinue metoprolol in patients with coronary artery disease 1
• Abrupt discontinuation causes severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 1
• Taper gradually over 1-2 weeks when discontinuing chronically administered metoprolol 1
• If angina markedly worsens during tapering, reinstate metoprolol immediately and implement measures for unstable angina 1

Surgical Patients

• Do not routinely withdraw chronically administered beta-blocker therapy prior to major surgery 1
• Recognize that impaired ability to respond to reflex adrenergic stimuli may augment risks of general anesthesia and surgical procedures 1

Pheochromocytoma

• Metoprolol must only be used with an alpha blocker in pheochromocytoma, and only after alpha blockade has been initiated 1

Special Population Considerations

Elderly Patients

• Topical and systemic co-administration of beta-blockers occurs frequently in elderly patients and may result in additive effects including bradycardia 4
• Excessive heart rate lowering in elderly patients may cause serious adverse events 4

Pregnancy

• Metoprolol is considered safe in pregnancy 4

Important Clinical Context

Despite these side effects, beta-blocker therapy in heart failure trials was associated with fewer all-cause medication withdrawals (14 per 1000 reduction) compared to placebo, along with significant reductions in mortality (34 per 1000), heart failure hospitalizations (40 per 1000), and worsening heart failure (52 per 1000) 3. The absolute increases in adverse effect risks are small relative to the substantial mortality and morbidity benefits 3.

For heart failure patients, only bisoprolol, carvedilol, and extended-release metoprolol succinate have proven mortality benefits; metoprolol tartrate should not be used in preference to these evidence-based formulations 2.