Ranolazine Loading to Prevent PCI-induced Myocardial Injury (TWILIGHT)

TWice overnIght High-dose ranoLazIne Pretreatment for preventinG Myocardial iscHemic Damage in Patients With Stable Angina Undergoing percuTaneous Coronary Intervention

It has previously been shown that pretreatment with ranolazine 1,000 mg twice daily for 7 days can significantly reduce procedural myocardial injury in elective percutaneous coronary intervention (PCI). The investigators tested the hypothesis that twice overnight high-dose ranolazine loading before PCI can reduce the peri-procedural myocardial ischemic damage similarly to long-term pre-treatment with standard doses.

Background Ranolazine is a novel antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia thus limiting ischemic injury. It has previously been shown that pretreatment with ranolazine 1,000 mg twice daily for 7 days can significantly reduce procedural myocardial injury in elective percutaneous coronary intervention. It remains unknown, however, which of these two therapeutic approaches is more effective after PCI. Purpose The primary objective of this study is to test the hypothesis that twice overnight high-dose ranolazine loading before PCI can reduce the peri-procedural myocardial ischemic damage similarly to long-term pre-treatment with standard doses.

Administration of two preprocedural doses of Ranolazine 12 hours apart (1,000 mg the night before PCI and 1,000 mg prior to PCI)

Occurrence of peri-procedural myocardial infarction (i.e. creatine kinase-MB>3 times the upper reference limit)

Changes after percutaneous coronary intervention in absolute values of creatine kinase, creatine kinase-MB, myoglobin, and troponin I

30-day incidence of major adverse cardiac events (MACE-death, myocardial infarction, target vessel revascularization)

Inclusion Criteria: Angiographically-proven coronary artery disease Class I indication to elective percutaneous coronary intervention Stable conditions No recent acute coronary syndromes Normal baseline values of markers of myocardial damage (creatine kinase, creatine kinase-MB, myoglobin, and troponin I) Able to understand and willing to sign the informed consent form Exclusion Criteria: • Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before