BACKGROUND: Despite advances in antithrombotic therapies and invasive 
technology, the risk of recurrent ischemic complications in patients with 
non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. 
Ranolazine is a novel agent that inhibits the late sodium current thereby 
reducing cellular sodium and calcium overload and has been shown to reduce 
ischemia in patients with chronic stable angina.
STUDY DESIGN: MERLIN-TIMI 36 is a phase III, randomized, double-blind, 
parallel-group, placebo-controlled, multinational clinical trial to evaluate the 
efficacy and safety of ranolazine during long-term treatment of patients with 
NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 
1:1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 
hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal 
insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched 
placebo until the end of study. The primary end point is the time to first 
occurrence of any element of the composite of cardiovascular death, myocardial 
infarction, or recurrent ischemia. Secondary end points include ischemia on 
Holter monitoring, hospitalization for new or worsening heart failure, quality 
of life measures, and exercise performance. The evaluation of long-term safety 
will include death from any cause and symptomatic documented arrhythmia. 
Recruitment began in October 2004. The trial will continue until 730 major 
cardiovascular events and 310 deaths are recorded with expected completion in 24 
to 28 months.
CONCLUSIONS: MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute 
and chronic management of patients presenting with NSTE-ACS.