A new retrospective cohort study published inJAMA Internal Medicinehas found that pregabalin, a commonly prescribed nonopioid analgesic, is associated with a significantly higher risk of heart failure events compared to gabapentin. The study analyzed Medicare claims data from a large population of older adults and observed that patients initiated on pregabalin had an elevated incidence of hospitalization due to heart failure. This risk was especially pronounced in individuals with pre-existing cardiovascular conditions. Both pregabalin and gabapentin are used to manage neuropathic pain, but pregabalin has a more potent pharmacologic profile and is often considered the stronger agent. However, this potency may come at the cost of increased cardiac risk. Researchers point out that the mechanism may be related to fluid retention and vasodilation effects, which are more commonly reported with pregabalin use. The findings highlight the need for careful patient selection when initiating pregabalin, particularly among older adults or those with a history of heart failure or compromised cardiac function. Clinicians are encouraged to consider alternative therapies such as gabapentin in patients with elevated cardiovascular risk and to closely monitor for early signs of fluid overload or cardiac symptoms if pregabalin is deemed necessary. While both drugs offer effective pain relief, the study underscores the importance of balancing analgesic efficacy with long-term safety, especially in vulnerable populations. These findings may influence prescribing guidelines and prompt further investigations into the cardiovascular safety profile of commonly used neuropathic pain medications. Keywords:pregabalin, gabapentin, heart failure, cardiovascular risk, Medicare, neuropathic pain, JAMA, older adults, drug safety, nonopioid analgesic