Exercise Training With and Without Ranolazine in Chronic Stable Angina Patients

Introduction: An estimated seven million American adults live with coronary artery disease and chronic angina. Many continue to experience angina despite revascularization and antianginal medications. Ranolazine reduces angina frequency and increases exercise capacity. We hypothesized that exercise plus ranolazine would allow patients to train at greater intensities, leading to improvements in exercise capacity (peak VO2), increased daily physical activity and improved quality of life (QOL).

Methods: Sedentary subjects with chronic stable angina were randomized to either ranolazine (n=14) or placebo (n=15) plus a 12-w exercise program. Exercise training was 3 days/w for 30-45 min/session. Peak VO2, physical activity (Actigraph) and QOL (Seattle Angina Questionnaire) were measured pre- and post-training.

Results: Peak VO2, daily physical activity and QOL were improved more with ranolazine than placebo. Due to the small size of this pilot study, there were no between-group significant differences. After 2w on drug, (before exercise training) peak VO2 increased to a greater extent in the ranolazine group: 0.38 (±1.9) mL/kg/min vs. 0.03 (±1.2) with placebo (both NS). Post-training, peak VO2 increased twice as much in the ranolazine group: 2.1 (±3.4) vs. 0.9 (±1.5) mL/kg/min (both P<0.05). Daily activity increased significantly (P<0.05) in the ranolazine group; no significant change occurred in the placebo group. QOL improved significantly after 2w (P<0.001) on ranolazine, but not with placebo. Both groups significantly improved QOL (P<0.05) post-training. However, the improvement in the ranolazine group (2.1±3.4) was more than twice that of the placebo group (0.9±1.5).

Conclusions: Although this pilot study was not powered to find a significant difference between groups, the results trend towards favoring ranolazine. This suggests the addition of ranolazine to an exercise program may improve fitness and increase daily physical activity beyond the results of an exercise program alone in chronic stable angina patients. Power calculations (power = 80%; alpha = 0.05) suggest a total sample of 254 (127 per group) would be needed to detect between group differences for changes in peak VO2 and QOL.

Sponsor: Duke University

Collaborator: Gilead Sciences