Can dofetilide be used in patients with acute coronary ischemia?

Dofetilide Should Not Be Used During Acute Coronary Ischemia

Dofetilide is contraindicated in the setting of acute coronary ischemia due to the substantially increased risk of torsades de pointes and sudden cardiac death when the arrhythmic substrate is acutely altered by ischemia. 1

Evidence from Guidelines and Clinical Experience

Acute Ischemia Dramatically Alters Proarrhythmic Risk

• The FDA label does not specifically address acute ischemia as a contraindication, but warns that QT prolongation is directly related to dofetilide plasma concentration and that factors affecting the arrhythmic substrate increase torsades de pointes risk. 2

• A case report documented marked QT prolongation and torsades de pointes in a patient on stable dofetilide therapy who developed acute myocardial ischemia with flash pulmonary edema, demonstrating that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia. 1

• The 2006 ACC/AHA/ESC guidelines note that in straightforward coronary artery disease populations without myocardial infarction or heart failure, it is uncertain whether the benefit of dofetilide outweighs risk, and more experience is needed before recommending it in these patients. 3

Post-MI vs. Acute Ischemia: Critical Distinction

• The DIAMOND-MI trial involved selected post-MI patients (not acute ischemia) in whom the antiarrhythmic benefit of dofetilide balanced the risk of proarrhythmic toxicity, making dofetilide a potential second-line agent only after stabilization. 3

• Guidelines specify that dofetilide may be considered in stable coronary artery disease patients, but emphasize this applies to stable patients, not those with ongoing acute coronary syndromes. 3

• Dofetilide was proven safe in patients with ejection fraction ≤35% in the DIAMOND trials, but these were stable outpatients, not patients with acute ischemia. 4

Clinical Algorithm for Decision-Making

Absolute Contraindications to Dofetilide Initiation:

1. Active chest pain or ongoing ischemia 1
2. ST-segment changes indicating acute coronary syndrome 3
3. Hemodynamic instability 3
4. QTc >500 ms (or >550 ms with ventricular conduction abnormalities) 4, 2

If Patient Is Already on Dofetilide and Develops Acute Ischemia:

1. Immediately discontinue dofetilide 1
2. Initiate continuous ECG monitoring for torsades de pointes 2
3. Correct electrolytes (potassium >4.0 mEq/L, normalize magnesium) 4
4. Treat the acute coronary syndrome per standard protocols (antiplatelet, anticoagulation, revascularization) 3
5. Do not restart dofetilide until the patient is stable, ischemia is resolved, and at least 48-72 hours have passed 1

Critical Pitfalls to Avoid

• Do not assume that because dofetilide was safe in DIAMOND-MI, it is safe during acute ischemia—the DIAMOND-MI patients were post-MI and stable, not acutely ischemic. 3

• Do not rely on a "normal" baseline QTc—acute ischemia can rapidly prolong the QT interval in patients on dofetilide, even if previously stable. 1

• Do not continue dofetilide during acute coronary syndrome management, as the combination of ischemia-induced electrophysiologic changes and dofetilide's IKr blockade creates a perfect storm for torsades de pointes. 1

Preferred Alternatives During Acute Ischemia

• Beta-blockers are the cornerstone of acute coronary syndrome management and provide both anti-ischemic and antiarrhythmic effects without the proarrhythmic risk of class III agents. 3

• Amiodarone may be used if urgent rhythm control is needed during acute ischemia, as it has a more favorable safety profile in this setting compared to pure class III agents like dofetilide. 3

• For rate control in atrial fibrillation during acute coronary syndrome, beta-blockers or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are preferred, avoiding dofetilide entirely. 3