Background: Persistent angina is prevalent in women, who more often present with atypical angina, and experience less relief from antianginal therapies. The impact of ranolazine on female-specific angina is unclear. A single-arm, open-label trial was conducted to quantify the impact of ranolazine on angina in women with ischemic heart disease (IHD). Materials and Methods: Women with IHD and ≥2 angina episodes/week were recruited from 30 U.S. sites. Angina and nitroglycerin (NTG) consumption were assessed using patient-reported diaries, Seattle Angina Questionnaire (SAQ), Duke Activity Score Index (DASI), and Women's Ischemia Symptom Questionnaire (WISQ) at baseline and at 4 weeks of treatment with ranolazine 500 mg twice/day. A modified intent-to-treat analysis and parametric or nonparametric methods were used as appropriate to analyze changes. Results: Of 171 women enrolled, mean age was 65 ± 12 years. Of the 159 women included in the analysis, at week 4 compared to baseline, median angina frequency decreased with ranolazine treatment from 5.0 to 1.5 attacks/week and median change from baseline was-3.3 (95% confidence interval [CI]:-4.0 to-2.5; p ≤ 0.0001). Median NTG consumption decreased from 2.0 to 0.0 per week over the 4 weeks and median change was-1.0 (95% CI:-2.0 to-0.5; p < 0.0001). All five SAQ subscales showed mean improvements: physical limitation 9.2 (standard error [SE] 1.5; p < 0.0001), angina stability 31.8 (SE 2.7; p < 0.0001), angina frequency 17.7 (SE 1.6; p < 0.0001), treatment satisfaction 9.3 (SE 1.6; p < 0.0001), and disease perception 2.9 (SE 0.8; p < 0.0001). DASI score also improved 2.9 (SE 0.8; p=0.0014). WISQ subscales also showed significant improvements (all p < 0.0001). Thirty-one women reported drug-related adverse events (AEs), predominantly mild to moderate gastrointestinal symptoms. Conclusions: Women with IHD treated with ranolazine for 4 weeks experienced less angina measured by SAQ and WISQ. NTG use decreased, physical activity improved, and treatment satisfaction improved. AEs were consistent with prior reports.
Bibliographical noteFunding Information:
PI and Institutions are Richard Ansinelli and Robert Touchon, King’s Daughter Medical Center, Ashland, KY; Nizar Assi, Gateway Cardiology, PC; St. Louis, MO and Jerseyville, IL; C. Noel Bailey Merz, Cedars-Sinai Medical Center, Los Angeles, CA; Vera Bittner, The University of Alabama Birmingham, Birmingham, AL; Rita Coram, University of Louisville, Louisville, KY; Ira Dauber, South Denver Cardiology Associates, PC, Littleton, CO; Ashwini Davuluri, Jacksonville Heart Center, Jacksonville, FL; John Detwiler, Escondido Cardiology Associates, Escondido, CA; Yaron Elad, Access Clinical Trials/Cardiovascular Research Institute (ACT/CVRI), Beverly Hills, CA; Angel Flores, TriState Medical Group, Cardiology, Beaver, PA; Garo Gar-ibian, Cardiology Consultants of Philadelphia, Philadelpia, PA; Harinder Gogia, Cardiology Consultants of Orange County, Anaheim, CA; Nieca Goldberg, Total Health Care, New York, NY; Oscar Guerra, Greater Metabolic Associates, Coral Gables, FL; Peter Hanley, Northern Indiana Research Alliance, Fort Wayne, IN; David Hassel, Jacksonville Heart Center, Jacksonville, FL; Ameer Kabour, Toledo Cardiology Consultant’s, Cardiac Research, Toledo, OH; Dean Ker-eiakes, The Lindner Clinical Trial Center, Cincinnati, OH; Michael Koren, Jacksonville Center for Clinical Research, Jacksonville, FL; Steven Krueger, Integrated Cardiology Consultants, LLC d/b/a Bryan LGH Heart Institute, Lincoln, NE; Pamela Rama, Jacksonville Heart Center, Jacksonville, FL; Peter Roan, Mercy Physician Group Cardiology, Nampa, ID; William Short, St. Luke Cardiology Associates, Jacksonville, FL; Brian Shortal, North Shore Cardiology, Bannockburn, IL; M. Thames, Cardiovascular Consultants Ltd, Phoenix, AZ; Gregory Thomas, Mission Internal Medical Group, Mission Viejo, CA; William Tinker, Bluestem Cardiology, Bartlesville, OK; Nanette Wenger, Emory University & Grady Health System, Atlanta, GA; David Wolinsky, Albany Associates in Cardiology, Albany, NY. Funding: This work was supported by contracts from CV Therapeutics/Gilead, the National Heart, Lung and Blood Institutes nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, K23HL105787, R01 HL090957, 1R03AG 032631 from the National Institute on Aging, GCRC grant MO1-RR00425 from the National Center for Research Resources, the National Center for Advancing Translational Sciences Grant UL1TR000124, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, and QMED, Inc., Laurence Harbor, NJ, the Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships, Cedars-Sinai Medical Center, Los Angeles, CA, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, The Society for Women’s Health Research (SWHR), Washington, DC, The Linda Joy Pollin Women’s Heart Health Program, and the Erika Glazer Women’s Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, CA.
© Mary Ann Liebert, Inc., publishers 2019.
- and heart disease