Could pregabalin increase heart failure (HF) incidence more than gabapentin among older adults with chronic pain? A retrospective cohort study, published in JAMA Network Open, analyzed Medicare claims from 246,237 beneficiaries aged 65 to 89 years with chronic noncancer pain and no prior HF or terminal illness. Data were collected between January 2015 and December 2018 and analyzed through December 2024.

Of these, 18,622 initiated pregabalin and 227,615 initiated gabapentin. During 114,113 person-years of follow-up, there were 1,470 HF-related hospitalizations or emergency department (ED) visits. The HF rate was 18.2 per 1,000 person-years for pregabalin versus 12.5 for gabapentin. After adjusting for 231 demographic, clinical, and utilization covariates, pregabalin use was associated with a 48% higher HF risk (adjusted hazard ratio [AHR], 1.48; 95% CI, 1.19–1.77). Among patients with cardiovascular disease, the risk increase was greater (AHR, 1.85; 95% CI, 1.38–2.47). Outpatient HF incidence was also higher (AHR, 1.27; 95% CI, 1.02–1.58). All-cause mortality did not differ significantly.

This study found increased HF incidence in older adults starting pregabalin versus gabapentin, especially with a cardiovascular disease history.