Elderly adults taking pregabalin for chronic pains presented a risk up to 85% heart failure than users of gabapentine, which increases a new caution for prescribing practices in high -risk groups.
Study: initiation of pregabalin vs gabapentine and development of heart failure. Image credit: Vector_leart / Shutterstock
In a recent study published in Jama Network OpenResearchers compared the incidence of heart failure (HF) between users of gabapentine and pregabalin.
Non-opioid drugs, such as gabapentine and pregabaline, are gabapentinoids (analogues of gamma-aminobutyric acid) prescribed for chronic pain disorders. They are preferred to opioids for chronic treatment of non -cancer pain due to the higher risks of overdose, dependence and death associated with opioids. Non-opioids are specifically indicated for the elderly, as they are among the most at risk of undesirable effects linked to opioids.
Gabapentine and pregabalin are linked to specific subunits of neural calcium channels of type N and P / Q type, reduce the release of neurotransmitters and have antinocceptive effects. However, unwanted cardiovascular effects, including peripheral edema and HF, have been associated with gabapentine and pregabalin due to their additional effects on α2δ subunits of Calcic channel lunities type L on cardiomyocytes and ventricular arteries.
In addition, the risk of undesirable effects can be higher with pregabalin compared to gabapentine because of its higher power and the affinity of the connection to receptors. However, there are only a few studies that have evaluated the risk of comparison HF between users of gabapentine and pregabalin. In addition, most of these studies have not focused on the elderly, have limited their analyzes to neurological indications, or lacked a rigorous HF definition.
To fill these gaps, the researchers used a target test emulation design, a frame that imitates a randomized controlled trial using observation data to estimate the more robust causal effects. They adjusted 231 covariables using the opposite probability of processing of treatment to minimize confusion.
About the study
In this study, the researchers compared the incidence of the IC in prescribed individuals gabapentine or pregabalin for chronic non -cancer pain. A sample of 20% of medical beneficiaries between January 1, 2015 and December 21, 2018 was included. The cohort included beneficiaries aged 65 to 89 and was limited to those who have ambulatory medical care, prescription drugs and hospital coverage. Patients registered in Medicare Advantage (Part C) were excluded due to incomplete complaint data.
Patients with a chronic pain diagnosis and new prescription for gabapentine or pregabalin were included in the cohort. People with terminal phase diseases, the history of the IC, hospitalization on the day of prescription, the stay in hospital over 29 days or a stay of more than 29 days in a long -term care establishment were excluded. The subjects were followed until a visit or hospitalization of the emergency service (hospitalization for HF, death or the end of the study.
The main result was a visit or hospitalization of the emergency for an HF primary diagnosis. The secondary results included ambulatory encounters with a primary HF diagnosis and a mortality of all causes combined. Risk ratios for gabapentine and pregabalin have been estimated using the proportional risk of COX. The models have been adjusted using the opposite probability of the weighting of treatment on the basis of a propensity score which incorporated 231 demographic, clinical and drug use variables. In addition, laminate analyzes have been carried out by sex, race, ethnic and history of cardiovascular diseases (MCV).
Results
The cohort included 246,237 beneficiaries of Medicare, with a 73 -year -old median age. Among these, 92.4% used gabapentine and 7.6% used pregabalin. Most participants were women (66.8%) and white (79.9%). Neuropathic, back and musculoskeletal pain was the most common diagnoses associated with gabapentine and pregabaline prescriptions. Gabapentine and pregabalin users had comparable comparable frequencies of diagnostic of cardiovascular and other conditions.
Nevertheless, pregabalin users had an increased prevalence of fibromyalgia, diabetic neuropathy, greater use of duloxetine inhibitors and cycloxygenase-2 and a lower proportion of white individuals. Overall, 1.3% of the cohort developed HF during a follow -up of 114,113 years of years. The HF incidence for 1,000 years was 12.5 for gabapentine users and 18.2 for pregabalin users.
Pregabalin was associated with a higher HF risk than gabapentin in women, whites and those who have history of MCV. In addition, the risk of ambulatory HF was significantly higher for pregabalin users compared to users of gabapentine. However, the mortality of all causes did not differ significantly between these groups.
In a negative control analysis using hip fracture, a condition unrelated to exposure or the result, no significant difference has been observed between the two drugs, supporting the specificity of the CI results. In addition, the electronic values have been calculated to assess robustness with unbeatored confusion.
Conclusions
In short, the initiation of pregabalin was associated with an increased risk of HF incident compared to the initiation of gabapentine in the elderly suffering from chronic pain. This risk was particularly pronounced in people with preexisting MCV, supporting the current prudence recommendations when prescribing pregabalin to the elderly with MCV.
The limits of the study include a biased sample towards women and whites, the restriction of the sample for people aged ≥ 65 years, the exclusion of the medicare admitted and the limited power for racial ethnic and minority groups. In addition, unbeatable confusion factors such as body mass index, smoking, physical activity and socioeconomic status were not available in the Medicare data set, but were partially treated with negative control and electronic value analyzes. Overall, clinicians should assess the current cardiovascular risk factors and provide adequate risk advice to the elderly before prescribing pregabalin for chronic pain.