Author + information
- Received November 12, 2010
- Revision received March 2, 2011
- Accepted March 4, 2011
- Published online May 1, 2011.
- Puja K. Mehta, MD⁎,
- Pavel Goykhman, MD⁎,
- Louise E.J. Thomson, MBChB†,
- Chrisandra Shufelt, MD, MS⁎,
- Janet Wei, MD⁎,
- YuChing Yang, PhD⁎,
- Edward Gill†,
- Margo Minissian, NP⁎,
- Leslee J. Shaw, PhD‡,
- Piotr J. Slomka, PhD†,
- Melissa Slivka, MD⁎,
- Daniel S. Berman, MD† and
- C. Noel Bairey Merz, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. C. Noel Bairey Merz, Cedars-Sinai Heart Institute, 444 South San Vicente Boulevard, Suite 600, Los Angeles, California 90048
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).
Dr. Slivka is currently at the Kaiser Permanente Medical Group. This work was supported by an unrestricted research grant from CV Therapeutics/Gilead and by contracts from the National Heart, Lung and Blood Institute, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164; a GCRC grant MO1-RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, the Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California, the Edythe L. Broad Women's Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California, and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles. The authors have reported that they have no relationships to disclose. Gregory Thomas, MD, MPH, served as Guest Editor for this article.
- Received November 12, 2010.
- Revision received March 2, 2011.
- Accepted March 4, 2011.
- American College of Cardiology Foundation