Abstract
BackgroundChronic pain affects 30% of all patients in developed countries, accounting for up to 35% of prescriptions in acute care settings. Non-opioid pain medications are widely utilized for treatment of non-cancer chronic pain. Among these, pregabalin is a commonly prescribed anticonvulsant, which works by antagonizing L-type calcium channels, decreasing the release of neurotransmitters[1]. Pregabalin use has been associated with reports of congestive heart failure (CHF), including peripheral and pulmonary edema[2-4]. However, the relationship between CHF incidence and pregabalin use among patients at the highest risk of adverse reactions (i.e., senior patients with various co-morbidities) remains unclear.ObjectivesTo compare incident CHF among new users of pregabalin versus gabapentin (the active comparator) in Medicare beneficiaries treated for non-cancer chronic pain.MethodsThis was a retrospective cohort study among Medicare beneficiaries aged 65-89 years old with chronic non-cancer pain, without prior history of CHF. We included patients who were newly prescribed users of pregabalin or gabapentin were followed up between 2015-2018. The outcome was incident CHF, ascertained by hospital admissions or emergency room visits with ICD 9 and or 10 codes in the first position codes. Inverse probability of treatment weighting was used to account for differences between pregabalin and gabapentin users in time-dependent analysis (i.e., Cox proportional-hazards regressions). Covariates used in the propensity scoring were selected based on prior knowledge and literature review, and included categories such as concurrent baseline cardiovascular, neurologic, pain, and psychiatric diagnoses and corresponding medications including opioids and antipsychotics. Non-diagnostic covariates were included, as well as demographics, socioeconomic status, and indicators/metrics of health care utilization.ResultsThis study included 17,756 new users of pregabalin and 221,053 new users of gabapentin. The cohort was predominantly female gender (66.7%), and non-Hispanic White (79.9%), with a median age of 73 (IQR: 69-78) years. The most common diagnostic indications for pregabalin and gabapentin were musculoskeletal and back pain. Prior to inverse probability weighting, pregabalin vs gabapentin users had higher daily short-acting opioid morphine equivalent doses (median; 18.0 vs 8.9 mg/d), higher use of coxibs (8.6% vs 4.9%), and higher prevalence of diabetic neuropathy (15.9% vs 11.3%) and fibromyalgia (19.9% vs 13.2%). After propensity score weighting, none of the covariates had a standardized difference>0.10. During 110,439 person-years of follow-up, 1,428 patients developed new CHF. The outcome rate for CHF incidence was 18.67 per 1000 person-years for pregabalin vs 12.57 per 1000-person years for gabapentin (adjusted HR 1.48 [95% CI, 1.20-1.81]).ConclusionIn this retrospective study of Medicare beneficiaries aged 65-89 years with chronic non-cancer pain, new users of pregabalin had higher rates of incident CHF hospitalizations or emergency room visits compared to new users of gabapentin.References[1]Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661-9.[2]Murphy N, Mockler M, Ryder M, Ledwidge M, McDonald K. Decompensation of chronic heart failure associated with pregabalin in patients with neuropathic pain. J Card Fail. 2007 Apr;13(3):227-9.[3]Page RL 2nd, Cantu M, Lindenfeld J, Hergott LJ, Lowes BD. Possible heart failure exacerbation associated with pregabalin: case discussion and literature review. J Cardiovasc Med (Hagerstown). 2008 Sep;9(9):922-5.[4]Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials. Epilepsia. 2011 Apr;52(4):826-36Acknowledgements:NIL.Disclosure of InterestsNone Declared.