Effects of Ivabradine on Myocardial Perfusion in Chronic Angina: A Prospective, Preliminary, Open-Label, Single-Arm Study.

Abstract

Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3months after initiation of treatment with ivabradine (- 2.9%; 95% confidence interval [CI] - 0.3 to - 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176s at baseline to 466 ± 136s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18-106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7bpm at baseline to 55 ± 8bpm at 3 months (p < 0.001). The mean SAQ-7 summary score improved from 69 ± 21 at baseline to 83 ± 12 at 3months (p = 0.001). No serious adverse effects were reported. Ivabradine added to beta blockers was associated with a reduction in detectable myocardial ischemia by MPS in patients with CA. Infographic available for this article. The trial has been retrospectively registered with the Brazilian Registry of Clinical Trials (REBEC) under the following number RBR-5fysqrh (date of registration: 30 November 2023).