Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia but No Obstructive Coronary Artery Disease

Study Questions:

Does ranolazine reduce angina symptoms among women with evidence of ischemia but with nonobstructive coronary artery disease (CAD)?


This was pilot study, designed as a double-blind, placebo-controlled, crossover trial. The study population comprised 20 women with angina, nonobstructive CAD, and ≥10% ischemic myocardium on adenosine stress cardiac magnetic resonance (CMR) imaging. Women were randomized to ranolazine or placebo for 4 weeks followed by a 2-week wash-out period. Outcomes were measured by Seattle Angina Questionnaire and CMR was evaluated after each treatment (ranolazine or placebo). 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).


The mean age of subjects was 57 ± 11 years. When on the ranolazine, women had higher Seattle Angina Questionnaire scores, including physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021) compared with placebo. A trend toward a higher CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074) was observed among women 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 (change in MPRI 0.48 vs. -0.82, p = 0.04).


The investigators concluded that among women with nonobstructive CAD and angina, ranolazine improves angina symptoms. 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.


This pilot study provides interesting data on a potential treatment for women with nonobstructive CAD and angina. For many clinicians, management of angina symptoms in this population can be challenging. Further study with a larger cohort and longer follow-up is warranted.

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Follow-Up Studies, Piperazines, Myocardium, Magnetic Resonance Spectroscopy

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