Holter Safety Data

Over 1 million hours of Holter data

• MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes–Thrombolysis in Myocardial Infarction 36) was a double-blind, randomized, placebo-controlled clinical trial of 6560 patients who presented within 48 hours of ischemic symptoms and who received intravenous ranolazine followed by Ranexa 1000 mg twice daily or placebo until the end of the study.³
• Enrolled patients were treated and followed for up to 24 months (median of approximately 1 year).³
• Ranexa did not achieve the primary efficacy endpoint of a reduction in the composite of cardiovascular death, myocardial infarction, or recurrent ischemia.³
• Ranexa is not approved for treatment of acute coronary syndrome.¹

Ranexa produced no proarrhythmic effects

• No proarrhythmic effects were observed with Ranexa during 7-day Holter monitoring in patients with acute coronary syndromes (n = 3162).¹
• Dose- and plasma concentration–related increases in the QTc interval (about 6 msec at 1000 mg twice daily), reductions in T-wave amplitude, and, in some cases, notched T waves have been observed in patients treated with Ranexa.¹
• At median follow-up of approximately 1 year, there was no difference between Ranexa and placebo in the risk of all-cause mortality (relative risk= 0.99).¹

Ranexa observations from 7-day Holter data

• There was a lower incidence of arrhythmias in patients treated with Ranexa twice daily plus standard of care (SOC) versus patients treated with placebo plus SOC
  (80% vs 87%).

• Arrhythmias were defined as ventricular tachycardia, new-onset atrial fibrillation, supraventricular tachycardia, and bradycardia.

• In post hoc analysis of patients with prior heart failure who enrolled in MERLIN-TIMI 36 (n = 1069), the incidence of ventricular tachycardia lasting at least 8 beats by day 7 of Holter monitoring was lower in patients receiving Ranexa twice daily compared with placebo (5.4% vs 9.3%).³

In MERLIN-TIMI 36, patients were on aspirin (96%), beta-blockers (89%), calcium channel blockers (30%), clopidogrel or ticlopidine (64%), statins (82%), and angiotensin II receptor blockers or ACE inhibitors (78%) at baseline.³

The difference in arrhythmias seen with Ranexa did not lead to reductions in mortality, arrhythmia hospitalization, or arrhythmia symptoms.¹

Warnings and Precautions

• Ranexa blocks I_Kr and prolongs the QTc interval in a dose-related manner.
• Clinical experience did not show an increased risk of proarrhythmia or sudden death.
• There is little experience with high doses (> 1000 mg twice daily) or exposure, with other QT-prolonging drugs, with potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation.