How safe and effective is ranolazine in the treatment of acute coronary syndromes?

Ranolazine (Ranexa) is no more effective than placebo in reducing adverse events in the treatment of acute coronary syndromes (ACS). (LOE = 1b)

Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes. The MERLIN-TIMI 36 randomized trial. JAMA 2007;297:1775-1783.  [PMID:17456819]

Randomized controlled trial (double-blinded)

Industry

Concealed

Inpatient (any location) with outpatient follow-up

Although ranolazine is effective for chronic angina, its efficacy and safety is unknown for ACS. These investigators enrolled 6560 adults, 18 years or older, presenting with ACS at 442 sites worldwide. The diagnosis of ACS was based on standard criteria (eg, pain at rest, pain lasting longer than 10 minutes, recent onset of pain, abnormal electrocardiogram result, elevated troponin levels, and so forth). Eligible patients randomly received (concealed allocation assignment) either ranolazine (200 mg intravenously over 1 hour, followed by an 80-mg per hour infusion for 12 to 96 hours, depending on response) or matched placebo. Doses were reduced appropriately for renal insufficiency. After the infusion, study medication was continued orally (1000 mg twice daily for active treatment or placebo). Individuals assessing outcomes remained blinded to treatment group assignment. The study was 90% powered to detect a 20% relative risk reduction in major outcomes at 1 year with ranolazine compared with placebo. In addition, patients received standard ACS follow-up treatments. Complete follow up occurred for more than 99% of patients for up to 24 months. Using intention-to-treat analysis, there was no significant difference between the 2 groups in the primary or secondary efficacy end points (composite of cardiovascular death, myocardial infarction, or recurrent/severe ischemia). The authors note a few secondary outcomes in which ranolazine was significantly superior to placebo, but it's important to remember that these results may appear spuriously significant simply by chance because of the measurement of multiple outcomes. There was no difference in all-cause mortality between the 2 groups. Drop-outs caused by adverse events (most frequently: dizziness, nausea, and constipation) occurred significantly more often in patients assigned to ranolazine.