OBJECTIVES: 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).
RCT Entities:
OBJECTIVES: 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: Janet Wei; Puja K Mehta; B Delia Johnson; Bruce Samuels; Saibal Kar; R David Anderson; Babak Azarbal; John Petersen; Barry Sharaf; Eileen Handberg; Chrisandra Shufelt; Kamlesh Kothawade; George Sopko; Amir Lerman; Leslee Shaw; Sheryl F Kelsey; Carl J Pepine; C Noel Bairey Merz Journal: JACC Cardiovasc Interv Date: 2012-06 Impact factor: 11.195
Authors: Mark A Marinescu; Adrián I Löffler; Michelle Ouellette; Lavone Smith; Christopher M Kramer; Jamieson M Bourque Journal: JACC Cardiovasc Imaging Date: 2015-02
Authors: Chrisandra L Shufelt; Louise E J Thomson; Pavel Goykhman; Megha Agarwal; Puja K Mehta; Tara Sedlak; Ning Li; Edward Gill; Bruce Samuels; Babak Azabal; Saibal Kar; Kamlesh Kothawade; Margo Minissian; Piotr Slomka; Daniel S Berman; C Noel Bairey Merz Journal: Cardiovasc Diagn Ther Date: 2013-09