Dr. Benjamin Morgan Scirica,
Ranolazine is an anti-anginal drug that reduces ischemia via inhibition of the late phase of the inward sodium current, which leads to a reduction in intracellular sodium and calcium overload. Increased intracellular calcium may precipitate electrical instability. In experimental models, ranolazine reduces pro-arrhythmic substrate and triggers, but the potential anti-arrhythmic actions of ranolazine have yet to be demonstrated in humans. The MERLIN-TIMI 36 trial randomized 6560 patients with NSTE-ACS to ranolazine or placebo in addition to standard therapy. Continuous ECG (cECG or Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. 6351 pts (97%) had cECG recordings evaluable for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting > 8 beats (166 [5.3%] v. 265 [8.3%], p<0.001), supraventricular tachycardia (1413 [44.7%] v. 1752 [55.0%], p<0.001), new-onset atrial fibrillation (55 [1.7%] v.75 [2.4%], p=0.08), or pauses > 3 seconds (97 [3.1%] v. 136 [4.3%], p=0.01).
Among patients admitted with NSTE-ACS, ranolazine reduced the rate of arrhythmias as assessed by cECG monitoring of patients in the first week after admission. These findings support the rationale for future prospective evaluations of ranolazine as an anti-arrhythmic therapy.
Clinical Trial Update II
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