Association between Ranolazine use and outcomes in patients with suspected MINOCA: A propensity-matched cohort study

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous clinical syndrome with limited evidence to guide secondary prevention. Ranolazine, a selective inhibitor of the late sodium current, improves coronary microvascular function and angina symptoms, yet its long-term prognostic value in MINOCA remains unclear.

To assess the association between ranolazine use and the risk of a composite outcome of all-cause mortality and heart failure exacerbation (HFE) in patients with MINOCA.

We conducted a retrospective cohort study using the TriNetX global health network, encompassing approximately 178 million patients from 156 healthcare organizations. Adults (≥18 years) diagnosed with suspected MINOCA identified based on administrative diagnostic coding between 2006 and 2025 were included. Patients treated with ranolazine were compared with non-users using 1:1 propensity score matching. The primary endpoint was a composite of all-cause mortality and HFE. Secondary endpoints included the individual components of the composite outcome.

Among 951,660 eligible patients, 2965 received ranolazine. After matching, 5930 balanced patients were analyzed. Ranolazine use was associated with a lower 3-year risk of the composite outcome (28.0% vs. 31.4%; HR 0.87, 95% CI 0.80-0.96; P = 0.005), mainly driven by fewer HFE (16.1% vs. 18.9%; HR 0.84, 95% CI 0.75-0.95; P = 0.006). All-cause mortality showed a nonsignificant trend toward benefit (HR 0.93; P = 0.26). Subgroup and sensitivity analyses supported result robustness.

In this real-world propensity-matched cohort, ranolazine use was associated with a significantly lower risk of the composite outcome of all-cause mortality and HFE, primarily driven by a reduction in HFE, suggesting potential prognostic benefits beyond symptom relief in MINOCA.