Author: Megan Brooks
Medscape Medical News
Pregabalin, a commonly prescribed antiseizure drug used for chronic pain, has been linked to an elevated risk of heart failure (HF), particularly in patients with preexisting cardiovascular disease (CVD). A large cohort analysis of more than 240,000 Medicare beneficiaries found that new users of pregabalin had a 48% higher risk of new-onset HF compared with those initiating gabapentin. In patients with a history of CVD, the risk was even higher—an 85% increased risk relative to gabapentin.
Over 114,000 person-years of follow-up, pregabalin users experienced 18.2 HF events per 1000 person-years versus 12.5 with gabapentin, translating to about six additional HF events annually per 1000 patients. Importantly, the risk was specific to heart failure events, as no difference in overall mortality was observed. Mechanistically, pregabalin may contribute to HF via sodium and water retention due to its stronger binding affinity to the α2δ subunit of L-type calcium channels.
These findings reinforce the European Medicines Agency’s caution regarding pregabalin in older adults with CVD and align with the American Heart Association’s classification of pregabalin (but not gabapentin) as a drug that may worsen heart failure.
What You Should Know
• Pregabalin initiation was associated with a significantly higher risk of HF compared with gabapentin.
• The risk was particularly pronounced in older adults with preexisting cardiovascular disease.
• No mortality difference was observed, but outpatient HF diagnoses also increased with pregabalin.
• Findings support guideline recommendations to use caution when prescribing pregabalin in older adults, especially those with CVD.
Practice Implication
For older adults with chronic noncancer pain—especially those with known CVD—clinicians should carefully weigh pregabalin’s analgesic benefits against its cardiovascular risks. Baseline cardiac assessment may be warranted, and gabapentin may represent a safer alternative in many cases.
References
Brooks M. August 07, 2025.
Thank you JAMA Network Open for allowing us to use this article.