title: Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease.
abstract: BACKGROUND
  Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient.
  
  
  METHODS
  Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy.
  
  
  RESULTS
  CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups.
  
  
  CONCLUSIONS
  Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.
authors.affiliation: Cardiology Division, "Umberto I" Hospital, Nocera Inferiore, Italy.
authors.forename: Ercole
authors.initials: E
authors.lastname: Tagliamonte
authors.forename: Fausto
authors.initials: F
authors.lastname: Rigo
authors.forename: Teresa
authors.initials: T
authors.lastname: Cirillo
authors.forename: Costantino
authors.initials: C
authors.lastname: Astarita
authors.forename: Gaetano
authors.initials: G
authors.lastname: Quaranta
authors.forename: Umberto
authors.initials: U
authors.lastname: Marinelli
authors.forename: Archimede
authors.initials: A
authors.lastname: Caruso
authors.forename: Carlo
authors.initials: C
authors.lastname: Romano
authors.forename: Nicola
authors.initials: N
authors.lastname: Capuano
mesh_terms: D002317:Cardiovascular Agents / Q000008:administration & dosage; D023921:Coronary Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy; D004311:Double-Blind Method; D004452:Echocardiography / Q000379:methods*; D005260:Female; D053805:Fractional Flow Reserve, Myocardial / Q000187:drug effects*; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000209:etiology; D015990:Placebo Effect; D000069458:Ranolazine / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D000069458:Ranolazine
keywords: coronary flow reserve; dipyridamole; ranolazine; stress echocardiography