Cardiovascular Risk Associated With Pregabalin Use in Older Adults With Chronic Pain

In the context of the growing search for non-opioid alternatives for chronic pain management, a retrospective cohort study by Park et al. analyzed data from over 246,000 Medicare beneficiaries between 2014 and 2018, all with chronic noncancer pain and no history of heart failure (HF). Of these, more than 18,000 were new pregabalin users and over 227,000 were new gabapentin users.

Results showed that pregabalin use was associated with a higher incidence of HF-related hospitalizations or emergency department visits compared with gabapentin (adjusted HR: 1.48; 95% CI: 1.19–1.77). Among patients with a history of cardiovascular disease, the risk was even greater (adjusted HR: 1.85; 95% CI: 1.38–2.47). An increase in outpatient HF diagnoses was also observed (adjusted HR: 1.27; 95% CI: 1.02–1.58), although no significant difference was found in all-cause mortality.

Mechanistically, pregabalin binds with greater affinity to α2δ subunits of voltage-gated calcium channels—also present in vascular smooth muscle and cardiac myocytes—potentially leading to fluid retention and exacerbation of subclinical cardiac dysfunction. The American Heart Association already lists pregabalin, but not gabapentin, as a drug that may worsen HF.

While the absolute increase in risk may appear modest—approximately 6 additional HF cases per 1,000 patients/year—the clinical impact is relevant given the severity of HF in older adults and the large population exposed. The authors highlight the need for caution when prescribing to individuals with baseline cardiovascular risk and consideration of cardiac evaluation prior to initiating treatment.

Editorial Note: This content was developed with the support of artificial intelligence technologies to optimize writing and information structure. All material was carefully reviewed, validated, and supplemented by human experts prior to publication, ensuring scientific accuracy and adherence to editorial best practices.

#HeartFailure #Pregabalin #Geriatrics #Cardiology #ChronicPain