A common painkiller is now under scrutiny. A new analysis of pregabalin vs gabapentin published in JAMA Network Open in August 2025 reports that pregabalin (brand name Lyrica), a widely used treatment for chronic nerve and back pain, is linked to a higher heart failure risk in older adults when compared head‑to‑head with gabapentin (brand name Neurontin). The signal is not trivial: the overall risk was about 48% higher, and it rose to 85% higher among people with established cardiovascular disease. For seniors taking multiple medications, this is a reminder to review pain management choices with a clinician and consider whether a safer option could achieve the same relief.
What are pregabalin and gabapentin?
Pregabalin and gabapentin are gabapentinoids that calm overactive nerve signaling. They are used for neuropathic pain (like diabetic neuropathy), fibromyalgia, and as adjuncts for seizures. In everyday practice, they often replace or reduce the need for opioids. Pharmacologically, pregabalin binds more tightly to the α2δ subunit of voltage‑gated calcium channels. That stronger binding is part of why it acts faster and at lower doses, but it may also promote sodium and water retention, a mechanism that can strain a vulnerable heart. Both medicines are common in adults over 65, especially for non‑cancer chronic pain.
The bigger picture: balancing pain relief and safety
Chronic pain affects a large share of older adults, and clinicians need non‑opioid options that are effective yet safe for people with heart or kidney conditions. Prescriptions for gabapentinoids have climbed since the opioid crisis, often appropriately. But any drug used widely in seniors deserves ongoing safety checks. Findings like these do not invalidate pregabalin. They simply clarify that not all options in a class carry the same risk profile, and that the patient’s cardiovascular risk should be part of the initial choice.
The study: a large Medicare cohort
Researchers at Columbia University analyzed 246,237 Medicare beneficiaries aged 65–89 with chronic pain and no prior heart failure. Within this group, 18,622 started pregabalin and 227,615 started gabapentin between 2014 and 2018. The team then tracked new heart failure events – hospitalizations or emergency‑department visits – after treatment initiation while adjusting for dozens of baseline factors.
Key results of pregabalin vs gabapentin
- Primary outcome: Heart failure hospitalizations/ED visits were 18.2 per 1,000 person‑years with pregabalin versus 12.5 with gabapentin—about 6 extra cases per 1,000 patients annually.
- Adjusted hazard ratio (aHR): 1.48 (95% CI, 1.19–1.77) overall; 1.85 (95% CI, 1.38–2.47) among patients with pre‑existing cardiovascular disease.
- Mortality: No significant difference was observed; outpatient diagnoses of heart failure rose modestly (aHR ~1.27).
Why the finding of increased risk matters
These results echo existing cautions from major authorities. The American Heart Association lists pregabalin among medications that can cause or worsen heart failure, and the European Medicines Agency advises caution in older adults with cardiovascular comorbidities. For a population already managing polypharmacy, an incremental risk matters, especially when a reasonable alternative like Neurontin may deliver similar pain relief for many patients.
Understanding the roots of the problem
Pregabalin’s high‑affinity calcium‑channel binding can reduce excitatory neurotransmission, easing neuropathic pain. Yet the same pathway can lead to fluid retention and edema. Extra fluid raises ventricular preload and may unmask latent heart dysfunction or accelerate early‑stage heart failure. Gabapentin, with lower binding affinity and different kinetics, appears to carry a lower signal for this specific risk in older adults.
What patients should know
- Do not stop suddenly. Abrupt pregabalin discontinuation can cause withdrawal symptoms or a pain rebound. Any changes should be supervised by a clinician.
- Watch for symptoms: new or worsening leg/ankle swelling, shortness of breath, sudden weight gain, rapid abdominal bloating, or unusual fatigue.
- Discuss alternatives: gabapentin, physical therapy, topical agents, targeted injections, or non‑opioid combinations tailored to cardiac and renal status.
- Review the full regimen: check for other drugs that can worsen fluid retention (e.g., certain diabetes drugs or NSAIDs) and assess salt intake.
IsraelPharm: access and affordability
Safe pain management depends on the right medicine at the right dose—plus the ability to obtain it consistently. IsraelPharm helps patients access prescription therapies such as gabapentin at competitive prices, with pharmacist guidance to avoid risky interactions and duplication. For seniors juggling multiple prescriptions, reliable supply and expert support are part of safer care.
Commentary and takeaways
Cardiology experts, including Dr. Robert Zhang (Weill Cornell Medicine) and Dr. Edo Birati (Tzafon Medical Center), called this analysis “timely and clinically relevant,” highlighting the need for vigilance when selecting non‑opioid pain therapy in older adults. The practical takeaway is straightforward: pregabalin remains useful, but in people 65+—especially those with heart disease—its initiation should trigger closer monitoring or consideration of alternatives. Shared decision‑making, medication reconciliation, and routine symptom checks can keep relief goals aligned with cardiovascular safety.
Frequently asked questions about the dangers of Lyrica (pregabalin)
Does this study mean pregabalin is unsafe for all seniors?
No. The study shows a relative increase in heart failure risk versus gabapentin, not a universal danger signal for everyone. For many patients without cardiovascular disease, and with strong reasons to prefer pregabalin, the benefits may still outweigh the risks. The important step doctors take is to consider heart history, current medicines, kidney function, and symptom monitoring when making the choice.
How big is the absolute risk increase from Lyrica vs Neurontin?
The difference translated to roughly 6 additional heart failure cases per 1,000 patients per year among new pregabalin users compared with gabapentin. That is meaningful at a population level, especially in Medicare‑aged adults, but the majority of individual patients will not develop heart failure. A doctor’s decisions would weigh symptom control against this incremental risk.
Why would pregabalin raise heart failure risk more than gabapentin?
Pregabalin’s stronger binding to neuronal calcium channels likely contributes to sodium and water retention, which can increase cardiac preload and precipitate or worsen heart failure in susceptible people. Gabapentin’s pharmacology appears to produce less fluid retention on average, which may explain the lower signal in older adults.
Should people already taking pregabalin switch to gabapentin?
Not automatically. Some patients respond far better to pregabalin, and a switch can cause symptom flare or withdrawal without careful tapering. A clinician can evaluate heart history, current symptoms, kidney function, and drug interactions. If risks are high or symptoms suggest fluid retention, a supervised transition to gabapentin or a non‑drug intervention may be appropriate.
Were deaths higher with pregabalin over the course of the sudy?
No clear mortality difference emerged in this analysis. The increased risk centered on new heart failure events that required emergency care or hospitalization and modestly more outpatient heart failure diagnoses. That pattern still matters, because early heart failure episodes can lead to repeated admissions and lower quality of life if not addressed.
What’s the bottom line for older adults with chronic pain?
Pain relief and heart health can both be protected. For people 65 and over, especially with existing cardiovascular disease, prescribers may prefer to start with gabapentin or choose pregabalin with closer monitoring for edema, shortness of breath, and rapid weight gain. Regular medication reviews, salt management, and non‑drug therapies can further reduce risk while keeping pain under control.
