Other Anti-Ischemic Interventions Ranolazine Ranolazine is an antianginal medication with minimal effects on heart rate and BP.260,261 It inhibits the late inward sodium cur- rent and reduces the deleterious effects of intracellular sodium and calcium overload that accompany myocardial ischemia.262 Ranolazine is currently indicated for treatment of chronic angina. The MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndromes-Thrombosis In Myocardial Infarction) 36 trial examined the efficacy and safety of ranolazine in 6560 patients with NSTE-ACS who presented within 48 hours of In a post hoc analysis in women, rano- lazine was associated with a reduced incidence of the primary endpoint (cardiovascular death, MI, or recurrent ischemia), principally owing to a 29% reduction in recurrent ischemia.116 In the subgroup with prior chronic angina (n=3565), ranola- zine was associated with a lower primary composite endpoint, a significant reduction of worsening angina, and increased Because the primary endpoint of the original MERLIN-TIMI 36 trial was not met, all additional analyses should be interpreted with caution. The recom- mended initial dose is 500 mg orally twice daily, which can be uptitrated to a maximum of 1000 mg orally twice daily. Ranolazine is usually well tolerated; its major adverse effects are constipation, nausea, dizziness, and headache. Ranolazine prolongs the QTc interval in a dose-related manner, but QTc prolongation requiring dose reduction was comparable with ranolazine and placebo in the MERLIN-TIMI 36 trial.263 See Online Data Supplement 13 for additional information on ranolazine. Intra-Aortic Balloon Pump (IABP) Counterpulsation IABP counterpulsation may be used in patients with NSTE- ACS to treat severe persistent or recurrent ischemia, especially in patients awaiting invasive angiography and revascular- ization, despite intensive medical therapy. In experimental studies, IABP counterpulsation increases diastolic BP and coronary blood flow and potentially augments cardiac output while diminishing LV end-diastolic pressure. 