title: Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease.
abstract: OBJECTIVE
  We conducted a pilot study for a large definitive clinical trial evaluating the impact of ranolazine in women with angina, evidence of myocardial ischemia, and no obstructive coronary artery disease (CAD).
  
  
  BACKGROUND
  Women with angina, evidence of myocardial ischemia, but no obstructive CAD frequently have microvascular coronary dysfunction. The impact of ranolazine in this patient group is unknown.
  
  
  METHODS
  A pilot randomized, double-blind, placebo-controlled, crossover trial was conducted in 20 women with angina, no obstructive CAD, and ≥ 10% ischemic myocardium on adenosine stress cardiac magnetic resonance (CMR) imaging. Participants were assigned to ranolazine or placebo for 4 weeks separated by a 2-week washout. The Seattle Angina Questionnaire and CMR were evaluated after each treatment. Invasive coronary flow reserve (CFR) was available in patients who underwent clinically indicated coronary reactivity testing. CMR data analysis included the percentage of ischemic myocardium and quantitative myocardial perfusion reserve index (MPRI).
  
  
  RESULTS
  The mean age of subjects was 57 ± 11 years. Compared with placebo, patients on ranolazine had significantly higher (better) Seattle Angina Questionnaire scores, including physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021). There was a trend toward a higher (better) CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074) on ranolazine. Among women with coronary reactivity testing (n = 13), those with CFR ≤ 3.0 had a significantly improved MPRI on ranolazine versus placebo compared to women with CFR > 3.0 (Δ in MPRI 0.48 vs. -0.82, p = 0.04).
  
  
  CONCLUSIONS
  In women with angina, evidence of ischemia, and no obstructive CAD, this pilot randomized, controlled trial revealed that ranolazine improves angina. Myocardial ischemia may also improve, particularly among women with low CFR. These data document approach feasibility and provide outcome variability estimates for planning a definitive large clinical trial to evaluate the role of ranolazine in women with microvascular coronary dysfunction. (Microvascular Coronary Disease In Women: Impact Of Ranolazine; NCT00570089).
authors.affiliation: Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Puja K
authors.initials: PK
authors.lastname: Mehta
authors.forename: Pavel
authors.initials: P
authors.lastname: Goykhman
authors.forename: Louise E J
authors.initials: LE
authors.lastname: Thomson
authors.forename: Chrisandra
authors.initials: C
authors.lastname: Shufelt
authors.forename: Janet
authors.initials: J
authors.lastname: Wei
authors.forename: Yuching
authors.initials: Y
authors.lastname: Yang
authors.forename: Edward
authors.initials: E
authors.lastname: Gill
authors.forename: Margo
authors.initials: M
authors.lastname: Minissian
authors.forename: Leslee J
authors.initials: LJ
authors.lastname: Shaw
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Slomka
authors.forename: Melissa
authors.initials: M
authors.lastname: Slivka
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berman
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D000241:Adenosine; D000368:Aged; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003326:Coronary Circulation; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015141:Los Angeles; D008279:Magnetic Resonance Imaging; D017566:Microvascular Angina / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D055414:Myocardial Perfusion Imaging; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D015990:Placebo Effect; D011788:Quality of Life; D000069458:Ranolazine; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents
chemical_list: D000083:Acetanilides; D002317:Cardiovascular Agents; D010879:Piperazines; D014665:Vasodilator Agents; D000069458:Ranolazine; D000241:Adenosine