Author + information
: In patients with coronary artery disease, the anti-ischemic effects of ranolazine, an inhibitor of the late sodium current (INa, L), are dose-dependent. In patients with long-QT syndrome 3 (LQT3) ranolazine causes a dose-dependent shortening of the QTc interval. We determined the relationship between QTc shortening in patients with LQT3 as a surrogate marker for inhibition of INa, L, and the anti-ischemic effects of ranolazine.
We performed a post-hoc analysis of pharmacodynamic and pharmacokinetic data from: 1) a study of the effect of ranolazine to shorten the QTc interval in patients with LQT3 (n=5); and 2) a randomized double-blind crossover study of the effect of ranolazine on exercise-induced ST depression in patients with CAD (n=191)
The relationships between the concentration of ranolazine and QTc shortening in LQT3 and time to 1mm ST-segment depression in CAD were linear (R2=0.91 and 0.88 respectively; Figure 1A). Similar correlations were obtained for other anti-ischemic effects of ranolazine (exercise duration, time to angina, and maximum ST depression). Using equations of best fit, a direct and linear relationship between QTc shortening and time to 1mm ST-segment depression was obtained (Figure 1B).
The linear correlation between the QTc interval shortening and the anti-ischemic effects of ranolazine support a common underlying mechanism of action, namely inhibition of late INa.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Anti-Ischemic Therapies
Abstract Category: 9. Chronic CAD/Stable Ischemic Heart Disease: Basic
Presentation Number: 1194-65
- 2013 American College of Cardiology Foundation