P204: Heart Failure Risk of Guideline-Recommended Pharmacotherapies Versus Gabapentin in Painful Diabetic Neuropathy: A Nationwide Cohort Study
Poster Presenter
Haeyoung Lee
Manager
Korea Institute of Drug Safety & Risk Management Korea, Republic of
Objectives
To compare the real-world risks of heart failure, myocardial infarction, and stroke associated with pregabalin and duloxetine versus gabapentin among adults with painful diabetic neuropathy in a nationwide cohort.
Method
We conducted a nationwide retrospective cohort study using the Korean National Health Insurance Service database. Adults with painful diabetic neuropathy who initiated pregabalin, duloxetine, or gabapentin between 2014 and 2018 were included. HF was the primary outcome; myocardial infarc
Results
After propensity score matching, pregabalin and gabapentin users showed comparable risks of myocardial infarction and stroke. However, pregabalin use was associated with a modest but statistically significant increase in heart failure risk compared with gabapentin (HR 1.06, 95% CI 1.03–1.09). The increased risk was more pronounced among patients aged <50 years and =70 years and demonstrated a clear duration–response pattern, with higher risks observed with longer treatment duration. Elevated HF risk persisted across dose strata and remained robust in lag-time sensitivity analyses.
Similarly, duloxetine use was associated with a significantly higher risk of HF compared with gabapentin (HR 1.11, 95% CI 1.05–1.17), while no significant differences were observed for myocardial infarction or stroke. Subgroup analyses indicated higher HF risk among younger and older patients, those receiving higher daily doses, and long-term users, particularly those treated for three years or longer. Lag-time analyses confirmed the primary findings.
Conclusion
In this nationwide cohort study, guideline-recommended agents for painful diabetic neuropathy, pregabalin and duloxetine, were associated with a modest but consistent increase in HF risk compared with gabapentin, while risks of myocardial infarction and stroke were largely comparable. The HF signal was more evident in specific subgroups and with longer treatment duration. Notably, duloxetine showed a statistically significant increase in HF risk despite the absence of such information in current international labeling, suggesting that consideration may be warranted for updating the “Adverse Reactions” section based on large-scale real-world evidence.
