A recent investigation has cast light on the differing cardiovascular safety profiles of two widely used medications, pregabalin and gabapentin, particularly among the elderly. This research suggests that older individuals undergoing treatment with pregabalin for persistent pain may encounter a heightened probability of developing heart failure when juxtaposed with those administered gabapentin. These findings necessitate a more circumspect approach to prescribing gabapalinoids, especially for vulnerable populations already predisposed to cardiac issues. The study emphasizes the critical need for healthcare providers to weigh the potential cardiac risks against the therapeutic benefits when selecting a pain management regimen for their elderly patients, advocating for more informed clinical decisions.

The study, featured in JAMA Network Open, conducted a comparative analysis of heart failure occurrences between individuals utilizing gabapentin and pregabalin. Both compounds, known as gabapentinoids, function as gamma-aminobutyric acid analogs and are commonly prescribed for various chronic pain syndromes. They represent an alternative to opioids, particularly favored for older adults due to opioids' substantial risks, including overdose and dependence. Despite their similar mechanism of action, involving the modulation of voltage-gated neuronal calcium channels to alleviate pain, these drugs also influence L-type calcium channel subunits on heart muscle cells and arteries, potentially leading to cardiovascular side effects such as peripheral edema and heart failure.

Prior research into the comparative cardiac risks of pregabalin versus gabapentin has been limited, often excluding older patient demographics, focusing solely on neurological conditions, or lacking stringent definitions of heart failure. To address these deficiencies, the current study employed a target trial emulation design, leveraging observational data to mirror a randomized controlled trial. This robust methodology allowed for a more accurate estimation of causal effects, controlling for 231 covariates through inverse probability of treatment weighting to mitigate confounding factors. The study cohort comprised a 20% sample of Medicare beneficiaries aged 65 to 89, spanning from January 2015 to December 2018, ensuring comprehensive coverage of medical, prescription, and hospitalization claims.

Participants were selected based on a chronic non-cancer pain diagnosis and the initiation of either gabapentin or pregabalin. Exclusions included patients with terminal illnesses, a history of heart failure, or recent hospitalizations, to ensure a focus on new-onset heart failure related to the medications. The primary endpoint was an emergency department visit or hospitalization attributed to a primary heart failure diagnosis. Secondary outcomes encompassed outpatient encounters for heart failure and all-cause mortality. Statistical analysis involved Cox proportional hazards regression, with adjustments for various demographic, clinical, and medication-use variables. Stratified analyses further examined differences across sex, race, ethnicity, and cardiovascular disease history.

The study's cohort consisted of 246,237 Medicare beneficiaries, predominantly female (66.8%) and White (79.9%), with a median age of 73. Gabapentin was used by 92.4% of the cohort, while pregabalin was used by 7.6%. Common pain diagnoses included neuropathic, back, and musculoskeletal pain. While cardiovascular and other health conditions were broadly comparable between the two groups, pregabalin users showed a higher prevalence of fibromyalgia and diabetic neuropathy. Over the observation period, 1.3% of the cohort developed heart failure. The incidence rate for heart failure was notably higher in pregabalin users (18.2 per 1,000 person-years) compared to gabapentin users (12.5 per 1,000 person-years). This heightened risk associated with pregabalin was more pronounced among women, White individuals, and those with a pre-existing history of cardiovascular disease. The risk of outpatient heart failure was also significantly elevated for pregabalin users, though no significant difference in all-cause mortality was observed between the two drug groups. The consistency of these findings was supported by negative control analyses and E-value calculations, reinforcing the specificity of the heart failure association.

The insights garnered from this investigation emphasize the increased potential for incident heart failure in older patients initiating pregabalin therapy for chronic pain, particularly when compared to gabapentin. This elevated risk is particularly salient for individuals already burdened with cardiovascular disease. Therefore, healthcare professionals are urged to conduct thorough assessments of cardiovascular risk factors before prescribing pregabalin to elderly patients and to engage in comprehensive discussions regarding the associated risks and benefits. This cautious approach will aid in optimizing treatment strategies and minimizing adverse cardiac outcomes within this susceptible demographic.