Ranolazine in patients with chronic coronary syndromes: real-world data provide new evidence on the antiarrhythmic properties of the drug

Aims: Ranolazine (Ran) is an anti-anginal drug inhibiting late sodium current, an action possibly hindering arrhythmias onset. Indeed, some evidence supports the anti-arrhythmic effects of Ran. The aim of this study, which evaluated Italian patients with chronic coronary syndrome (CCS), was to investigate whether Ran, as an add-on therapy, was associated with a lower incidence of atrial fibrillation (AF) compared to no Ran prescription (No-Ran). Methods and results: The original population (N=6.1 million) derived from the databases of the Italian National Health System; information concerned hospitalizations with the related diagnoses, drug therapy, follow-up clinical events and visits. Patients hospitalized between 2011 and 2020 for any cause and discharged with an ICD-9-CM CCS code were studied if AF had not been diagnosed before. The follow-up duration was 4.4 and 5.0 years for the Ran and the No-Ran cohorts, respectively.Study subjects were 171,015 (mean age: 72 years; men: 66%; Ran: N=22,207; No-Ran: N=148,808). After propensity score matching, Ran (N=6,384) and No-Ran (N=25,536) cohorts were similar for age, sex, comorbidities and drug therapy. AF incidence during follow-up was 5.3% and 9.6% in the Ran and in the No-Ran cohorts, respectively, with a 41% drug-related lower risk of arrhythmia development in the Cox model (HR=0.59, 95%CI: 0.53-0.67, p<0.001). Also, Ran correlated with reduced incidence of brady-arrhythmias (p=0.001) and ventricular tachy-arrhythmias (p=0.049), and with lower mortality (p<0.001). Conclusion: Our study, performed in a subset of the Italian CCS population, showed that Ran therapy was safe and associated with a long-term reduced AF incidence.