Mexiletine Use in Patients with History of Myocardial Infarction or Heart Failure
Mexiletine should NOT be used in patients with a history of myocardial infarction or structural heart disease, including heart failure, except in life-threatening ventricular arrhythmias refractory to other treatments. 1, 2
Critical Contraindications Based on CAST Trial Results
The FDA boxed warning explicitly states that sodium channel blockers like mexiletine increased mortality in post-MI patients in the landmark CAST trial (7.7% vs 3.0% in placebo). 2 This finding fundamentally changed antiarrhythmic prescribing:
- Prophylactic use is contraindicated: International consensus guidelines explicitly recommend against prophylactic antiarrhythmics in suspected acute coronary syndromes or MI. 1
- Post-MI patients are at increased risk: The 2015 ESC guidelines note that sodium channel blockers, including mexiletine, showed trends toward increased mortality in post-MI populations, similar to the CAST trial results with flecainide. 1
- Reserve for life-threatening arrhythmias only: The FDA label restricts mexiletine use to patients with life-threatening ventricular arrhythmias, explicitly excluding those with asymptomatic non-life-threatening arrhythmias. 2
Heart Failure Considerations
Mexiletine should be used with extreme caution or avoided in heart failure patients due to multiple safety concerns:
- The FDA label warns that mexiletine can aggravate hypotension and severe congestive heart failure. 2
- The American Heart Association recommends caution in heart failure patients as mexiletine may exacerbate the condition in susceptible individuals. 3
- Hepatic impairment secondary to heart failure prolongs mexiletine's elimination half-life (14-16 hours vs 10-14 hours), requiring dosage adjustment and careful monitoring. 3, 2
When Mexiletine MAY Be Considered (Narrow Exceptions)
Mexiletine has only two guideline-supported indications in patients with structural heart disease:
1. Hypertrophic Cardiomyopathy with Recurrent Ventricular Arrhythmias
- Class I recommendation from 2020 AHA/ACC guidelines for symptomatic ventricular arrhythmias or recurrent ICD shocks despite beta-blocker therapy. 1
- Mexiletine is listed alongside amiodarone, dofetilide, and sotalol as acceptable options. 1
- Choice should be guided by age, comorbidities, disease severity, and patient preferences. 1
- Evidence shows mexiletine is less effective than amiodarone (10.3% vs 38.5% shock rate) but has fewer adverse effects. 1
2. Refractory Life-Threatening Ventricular Arrhythmias
- May be used in 20-50% of patients with sustained ventricular tachycardia or fibrillation refractory to other treatments. 4
- Often combined with other antiarrhythmics (propranolol, quinidine, or amiodarone) to enhance efficacy. 5
- Requires continuous ECG monitoring during initiation. 3
Absolute Contraindications
Do not use mexiletine in patients with: 3, 2
- Severe sinus node dysfunction without pacemaker
- Marked sinus bradycardia without pacemaker protection
- Second or third degree AV block without continuous monitoring and operative pacemaker
- Severe liver disease (requires dosage adjustment if used)
Monitoring Requirements
If mexiletine must be used despite structural heart disease: 3, 2
- ECG monitoring is essential during initiation, particularly with other antiarrhythmics
- Monitor for worsening arrhythmias (proarrhythmic effect occurs in 10-15% of patients with life-threatening arrhythmias) 2
- Check liver function tests regularly (SGOT elevations >3x normal occur in ~1% of patients) 2
- Monitor for blood dyscrasias (leukopenia, thrombocytopenia reported in 0.06-0.16% of patients) 2
- Watch for neurological adverse effects (tremor, ataxia, dizziness) and cardiac effects (AV block, heart failure exacerbation) 3
Clinical Bottom Line
The default answer is NO - mexiletine should not be used in post-MI or heart failure patients except in the rare scenario of life-threatening ventricular arrhythmias that have failed safer alternatives, and only with intensive monitoring. 1, 2 The CAST trial mortality data and subsequent guideline recommendations have relegated mexiletine to a highly restricted role in modern cardiology practice.