Ranolazine Use in R-on-T ECG Patterns
Ranolazine is contraindicated in patients with QT-prolonging conditions, which includes R-on-T phenomena, as this drug causes dose-dependent QT prolongation and should not be used in patients with pre-existing electrical instability. 1
Critical Contraindication
The FDA label explicitly states that ranolazine is contraindicated in patients with QT-prolonging conditions. 2 The R-on-T pattern represents a dangerous form of electrical instability where premature ventricular contractions fall on the vulnerable period of the preceding T wave, creating high risk for ventricular tachycardia or ventricular fibrillation.
Mechanism of QT Prolongation
Ranolazine causes dose-related QT interval prolongation through inhibition of the rapid delayed rectifier potassium current (IKr), which prolongs the ventricular action potential. 3, 4
The relationship between ranolazine plasma concentration and QTc is linear, with a slope of approximately 2.6 msec per 1000 ng/mL. 2
At therapeutic doses of 1000 mg twice daily, the mean QTc prolongation is about 6 msec, but in the 5% of patients with highest plasma concentrations, QTc prolongation reaches at least 15 msec. 2
Clinical Risk Assessment
Patients with R-on-T patterns already demonstrate electrical instability and repolarization abnormalities, making additional QT prolongation particularly hazardous. 2
While torsades de pointes has not been observed at therapeutic doses in clinical trials, this was in patients without baseline QT-prolonging conditions. 3, 4
The ACC/AHA guidelines specifically note that ranolazine is contraindicated in patients with QT-prolonging conditions. 1
Important Clinical Pitfall
Do not confuse ranolazine's antiarrhythmic effects (reduced ventricular tachycardia, supraventricular tachycardia, and new atrial fibrillation in acute coronary syndrome patients) with safety in patients who have baseline electrical instability. 5 The antiarrhythmic effects observed in MERLIN-TIMI 36 occurred in patients without contraindications to ranolazine use, not in those with pre-existing QT prolongation or R-on-T patterns.
Alternative Management
For patients with chronic angina who have R-on-T patterns or other electrical instability, use standard antianginal agents that do not prolong QT interval, such as beta-blockers (first-line), calcium channel blockers (diltiazem or verapamil if no heart failure), or long-acting nitrates. 1
Address the underlying cause of the R-on-T pattern (ischemia, electrolyte abnormalities, structural heart disease) before considering any antianginal therapy. 1