Pregabalin Raises Heart Failure Risk In Older Adults Compared To Gabapentin, Study Finds

Older adults taking pregabalin for chronic symptom had up to an 85% higher consequence of bosom nonaccomplishment than gabapentin users, raising caller be aware for prescribing practices successful high-risk groups.

Study: Initiation of Pregabalin vs Gabapentin and Development of Heart Failure. Image Credit: Vector_Leart / Shutterstock

In a caller study published successful JAMA Network Open, researchers compared bosom nonaccomplishment (HF) incidence betwixt users of gabapentin and pregabalin.

Non-opioid medications, specified arsenic gabapentin and pregabalin, are gabapentinoids (analogs of gamma-aminobutyric acid) prescribed for chronic pain disorders. They are preferred complete opioids for chronic non-cancer symptom curen owed to nan higher risks of overdose, addiction, and decease associated pinch opioids. Non-opioids are specifically indicated for older individuals, arsenic they are among those pinch nan astir consequence for adverse effects related to opioids.

Both gabapentin and pregabalin hindrance circumstantial subunits of N-type and P/Q-type voltage-gated neuronal calcium channels, trim neurotransmitter release, and grounds antinociceptive effects. However, adverse cardiovascular effects, including peripheral edema and HF, person been associated pinch gabapentin and pregabalin owed to their further effects connected α2δ subunits of L-type calcium transmission subunits connected ventricular cardiomyocytes and arteries.

Moreover, nan consequence of adverse effects whitethorn beryllium higher pinch pregabalin compared to gabapentin owed to its higher potency and receptor binding affinity. However, location are only a fewer studies that assessed nan comparative HF consequence betwixt gabapentin and pregabalin users. In addition, astir of these studies did not attraction connected older individuals, constricted their analyses to neurological indications, aliases lacked a rigorous HF definition.

To reside these gaps, nan researchers utilized a target proceedings emulation design, a model that mimics a randomized controlled proceedings utilizing observational information to estimate causal effects much robustly. They adjusted for 231 covariates utilizing inverse probability of curen weighting to minimize confounding.

About nan study

In nan coming study, researchers compared nan incidence of HF among individuals prescribed gabapentin aliases pregabalin for chronic non-cancer pain. A 20% sample of Medicare beneficiaries betwixt January 1, 2015, and December 21, 2018, was included. The cohort comprised beneficiaries aged 65–89 and was constricted to those pinch outpatient aesculapian care, medicine drug, and hospitalization coverage. Patients enrolled successful Medicare Advantage (Part C) were excluded owed to incomplete claims data.

Patients pinch a chronic symptom test and a caller medicine of gabapentin aliases pregabalin were included successful nan cohort. Individuals pinch terminal illnesses, a history of HF, hospitalization connected nan time of prescription, infirmary enactment much than 29 days, aliases a enactment much than 29 days astatine a semipermanent attraction installation were excluded. Subjects were followed up until an emergency section (ED) sojourn aliases hospitalization for HF, death, aliases nan extremity of nan study.

The superior result was an ED sojourn aliases hospitalization for a superior HF diagnosis. Secondary outcomes included outpatient encounters pinch a superior HF test and all-cause mortality. Hazard ratios for gabapentin and pregabalin were estimated utilizing Cox proportional hazards regression. The models were adjusted utilizing inverse probability of curen weighting based connected a propensity people that incorporated 231 demographic, clinical, and medication-use variables. Further, stratified analyses were performed by sex, race, ethnicity, and history of cardiovascular illness (CVD).

Findings

The cohort comprised 246,237 Medicare beneficiaries, pinch a median property of 73. Of these, 92.4% utilized gabapentin and 7.6% utilized pregabalin. Most participants were female (66.8%) and White (79.9%). Neuropathic, back, and musculoskeletal symptom were nan astir communal diagnoses associated pinch gabapentin and pregabalin prescriptions. Gabapentin and pregabalin users had wide comparable frequencies of diagnoses of cardiovascular and different conditions.

Nevertheless, pregabalin users had an accrued prevalence of fibromyalgia, diabetic neuropathy, greater usage of duloxetine and cyclooxygenase-2 inhibitors, and a little proportionality of White individuals. Overall, 1.3% of nan cohort developed HF during a follow-up of 114,113 person-years. HF incidence per 1,000 person-years was 12.5 for gabapentin users and 18.2 for pregabalin users.

Pregabalin was associated pinch a higher HF consequence compared to gabapentin successful females, White individuals, and those pinch a CVD history. Further, nan consequence of outpatient HF was importantly higher for pregabalin users compared to gabapentin users. However, all-cause mortality did not importantly disagree betwixt these groups.

In a antagonistic power study utilizing hep fracture, a information unrelated to nan vulnerability aliases outcome, nary important quality was observed betwixt nan 2 drugs, supporting nan specificity of nan HF findings. Additionally, E-values were calculated to measure robustness to unmeasured confounding.

Conclusions

In sum, pregabalin initiation was associated pinch an accrued consequence of incident HF compared to gabapentin initiation successful older individuals pinch chronic pain. This consequence was particularly pronounced among individuals pinch pre-existing CVD, supporting existent recommendations for be aware erstwhile prescribing pregabalin to older group pinch CVD.

The study’s limitations see a sample skewed toward female and White individuals, sample regularisation to those aged ≥ 65, removal of Medicare Advantage enrollees, and constricted powerfulness for taste and group number groups. Furthermore, unmeasured confounders specified arsenic assemblage wide index, smoking, beingness activity, and socioeconomic position were not disposable successful nan Medicare dataset but were partially addressed done antagonistic power and E-value analyses. Overall, clinicians should measure ongoing cardiovascular consequence factors and supply capable risk-benefit counseling to older group earlier prescribing pregabalin for chronic pain.