Metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute coronary syndromes (MERLIN TIMI-36) study.
Ranolazine is a piperazine derivative believed to reduce anginal symptoms by preventing ischemia-mediated sodium and calcium overload in myocardial cells through inhibition of the late sodium current (late INa). Three small studies demonstrated the antianginal efficacy of ranolazine alone and in combination with betablockers or calcium channel blockers on conventional end points such as total exercise duration and time to ischemia/angina on a treadmill; however, questions of safety related to QT prolongation, efficacy in women and potential utility in higher risk populations remained. Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction (MERLIN-TIMI) 36 was a large randomized, double-blind, placebo-controlled trial, which evaluated the efficacy and safety of ranolazine initiated acutely and continued as chronic therapy following a non-ST-segment elevation acute coronary syndrome event. A total of 6560 patients were randomized 1:1 to ranolazine or placebo; the primary efficacy end point of the trial was a composite of cardiovascular death, myocardial infarction or recurrent ischemia. The key safety end points were death from any cause and symptomatic documented arrhythmia. Although statistically significant differences between the ranolazine and placebo groups were not reached in the primary efficacy analysis or in the major secondary outcome end point analyses (cardiovascular death, myocardial infarction or severe recurrent ischemia), the individual component of recurrent ischemia was significantly reduced by ranolazine, and ranolazine was demonstrated to be safe.
Melloni
Chiara
C
Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA. mello004@mc.duke.edu
Newby
L Kristin
LK
D000083:Acetanilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000517:prevention & control; D000208:Acute Disease; D000787:Angina Pectoris / Q000188:drug therapy; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine; D012008:Recurrence; D012737:Sex Factors; D015912:Thrombolytic Therapy
D000083:Acetanilides; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine