Pregabalin Tied to Elevated Heart Failure Risk

  1. Comparing Gabapentinoids

    The study compared the gabapentinoids pregabalin and gabapentin in relation to increased HF risk. Both medications are among the most commonly prescribed antiseizure medications used off-label to treat chronic neuropathic pain.

  2. Purpose and Function

    Nerve injury increases a neuron’s production of the α₂δ subunit, the auxiliary protein that directs calcium channel movement. Pregabalin and gabapentin bind to the α₂δ subunit, reducing calcium influx at presynaptic terminals, thereby dampening pain signaling.

  3. Which Manages Pain Better?

    Pregabalin and gabapentin both bind to the α₂δ subunit of voltage-gated calcium channels, but pregabalin has a higher binding affinity, greater potency at lower doses, and more predictable absorption, which can translate into stronger and more consistent analgesic effects.

  4. Study Overview: Method and Results

    The study’s cohort included 246,237 Medicare beneficiaries aged 65-89 with no history of HF. Of these individuals, 18,622 and 227,615 were newly prescribed pregabalin and gabapentin, respectively. Researchers used the inverse probability of treatment weighting method to approximate a randomized trial. Data analysis of 114,113 person-years of follow-up showed that a total of 1470 patients experienced HF events, with incidence rates of 18.2% per 1000 person-years for pregabalin and 12.5 per 1000 person-years for gabapentin.

  5. Pregabalin’s Link to HF

    Pregabalin is more frequently associated with peripheral edema and weight gain than gabapentin, which may contribute to fluid retention and increased cardiac workload. However, the precise mechanism linking pregabalin to heart failure risk has not been established.

    Thus, While pregabalin may provide more effective pain relief than gabapentin, its use is associated with a higher risk for HF in older adults, particularly those with preexisting cardiovascular disease. Clinicians should weigh this risk when prescribing pregabalin and consider monitoring or alternative therapies for high-risk patients.

     

    https://www.medscape.com/s/viewarticle/pregabalin-tied-elevated-heart-failure-risk-2025a1000o3y

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