Pregabalin vs Gabapentin Heart Failure Risk: JAMA 2025 Study Explained

Pregabalin vs Gabapentin just became breaking medical news: a large JAMA Network Open study (Sept 2025) found pregabalin users aged 65–89 had a ~48% higher risk of incident heart failure compared with gabapentin users—risk rising to ~85% in people with prior cardiovascular disease.

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Why this Pregabalin vs Gabapentin study matters in 2025

“Gabapentinoids” are widely used for nerve pain, fibromyalgia, and adjunct seizure control. Until now, most Pregabalin vs Gabapentin debates focused on speed, potency, and sedation/edema. The new 2025 study adds a cardiovascular safety signal: pregabalin was linked to higher new-onset heart failure vs gabapentin in older adults—reshaping first-line choices for seniors and those with CVD. JAMA Network

External context aligns with prior cautions: EMA product info already advises caution for pregabalin regarding congestive heart failure—especially in elderly with cardiovascular compromise. European Medicines Agency (EMA)

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Key numbers at a glance

Pregabalin vs Gabapentin heart-failure risk (primary outcome)

• HF events per 1,000 person-years: 18.2 (pregabalin) vs 12.5 (gabapentin)
• Adjusted Hazard Ratio (AHR): 1.48 (95% CI 1.19–1.77) → ~48% higher risk with pregabalin. European Medical Journal

Higher risk in people with prior heart/vascular disease

• AHR 1.85 (95% CI 1.38–2.47)—about 85% higher risk on pregabalin. European Medical Journal

Outpatient HF diagnoses also higher

• AHR 1.27 (95% CI 1.02–1.58). 2 Minute Medicine

Mortality in this timeframe

• No statistically significant difference in all-cause mortality (AHR ~1.26; 95% CI 0.95–1.76). PubMed

A JAMA editorial underscores the clinical relevance of this signal for older, multimorbid pain populations. JAMA Network

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What the researchers actually did

• Design: Retrospective cohort using U.S. Medicare data (2015–2018), new users of pregabalin or gabapentin with chronic non-cancer pain, aged 65–89 (history of HF excluded to measure incident HF).
• Confounding control: Inverse probability of treatment weighting across >200 covariates (age, sex, comorbidities, meds).
• Follow-up: ~114,113 person-years; N ≈ 246,000; median age ≈ 73; ~67% female.

Bottom line: Not a randomized trial (association ≠ causation), but large sample, careful adjustment, consistent effect sizes across outcomes make this a credible safety signal—especially in seniors with CVD. JAMA Network

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What this means for patients

If you’re 65+ or have heart disease, this study suggests gabapentin may be safer than pregabalin for heart-failure risk. Watch for edema, breathlessness, sudden weight gain, orthopnea—symptoms that can herald fluid overload. Mayo Clinic

Helpful internal tools while discussing options with your clinician:

• Check meds & interactions with the AI Prescription Checker → mymedicineadvisor.com/ai-prescription-checker
• Track weight/BMI trends (fluid retention concern) → BMI Calculator
• Log symptoms systematically → Symptom Checker

Do not stop pregabalin abruptly—taper under supervision to avoid withdrawal or seizure risk. Mayo Clinic

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What clinicians should change this week

• Prefer gabapentin over pregabalin as first-line in older adults and those with CVD, where efficacy is acceptable.
• If pregabalin is essential (e.g., prior gabapentin failure), start lowest effective dose, monitor weight/edema, and arrange early follow-up (2–4 weeks).
• Align with regulatory cautions (EMA CHF warnings) and educate patients on HF red-flags. European Medicines Agency (EMA)

Clinical synopsis pieces for quick briefing: 2-Minute Medicine and EMJ Cardiology have succinct summaries aligned with the JAMA data. 2 Minute Medicine

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Should you switch from pregabalin to gabapentin?

Switching can reduce HF risk exposure in older/CVD patients per the new association, but switching should be personalized:

• Shared decision: weigh pain control vs. cardiac risk.
• Taper strategy (example, not medical advice): gradually down-titrate pregabalin while up-titrating gabapentin, adjusting for renal function and sedation; monitor edema/weight weekly for the first month.
• Use internal tools: dose discussions with the Medicine Dosage Calculator and symptom logs via the Symptom Checker support safer transitions.
  • Medicine Dosage Calculator
  • Symptom Checker

Note: This study shows association, not causation; individual responses vary. Always switch under clinician supervision. JAMA Network

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How Pregabalin vs Gabapentin Actually Work

Both pregabalin vs gabapentin are gabapentinoids, designed as chemical cousins of the calming neurotransmitter GABA. But contrary to the name, neither binds to GABA receptors. Instead, they target the α2δ subunit of voltage-gated calcium channels, reducing the release of pain-signaling neurotransmitters such as glutamate and substance P. (NIH PMC)

• Gabapentin: Discovered earlier, it has variable bioavailability—higher doses lead to proportionally less absorption.
• Pregabalin: Engineered later, it shows ≥90% predictable absorption across all dose ranges, which explains its faster onset and stronger clinical effect. (Mayo Clinic)

👉 Why it matters: In real life, this means pregabalin may kick in within hours to days, while gabapentin often requires weeks of titration to show stable benefit.

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Approved Uses in 2025

When comparing pregabalin vs gabapentin, it’s essential to look at official approvals across major regulators.

• Gabapentin is FDA-approved for:
  • Partial seizures (as adjunctive therapy)
  • Post-herpetic neuralgia (nerve pain after shingles)
• Pregabalin is FDA-approved for:
  • Neuropathic pain (diabetic neuropathy, post-herpetic neuralgia)
  • Fibromyalgia (gabapentin isn’t FDA-approved here)
  • Partial seizures (adjunct)
  • Generalized Anxiety Disorder (in Europe, not US) (EMA)

👉 For everyday patients, this means: if your main issue is fibromyalgia, pregabalin is often prescribed first; if it’s shingles nerve pain, both are options.

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Effectiveness in Pain Relief

Clinical trials reveal nuanced differences when we pit pregabalin vs gabapentin head-to-head.

• In neuropathic pain, pregabalin consistently shows faster and stronger reductions in pain scores. A 2024 meta-analysis found pregabalin improved quality of life sooner than gabapentin, although long-term differences narrowed. (PubMed)
• For fibromyalgia, pregabalin is the only FDA-approved gabapentinoid, backed by multiple randomized controlled trials. Gabapentin has supportive evidence, but it remains off-label. (NIH)
• In seizure management, both are adjuncts, but neurologists often prefer pregabalin for its predictability—especially in patients who struggle with gabapentin absorption.

👉 Internal support: Patients exploring whether pain stems from neuropathy can use our Symptom Checker to discuss treatment options more clearly with their doctor.

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Dosing Differences

When comparing pregabalin vs gabapentin, dosing and titration speed are huge practical distinctions.

• Gabapentin: Usually started at 300 mg/day and slowly escalated to 900–3600 mg/day, split into 3 doses. Because of non-linear absorption, doubling the dose doesn’t double blood levels. (Drugs.com)
• Pregabalin: Typical range is 150–600 mg/day, split into 2–3 doses. Its linear absorption makes dose adjustment much simpler, which is why doctors often say it’s easier to “dial in.”

👉 For elderly or those with kidney issues, both require dose reductions, since they’re excreted unchanged by the kidneys. That’s where our Kidney Health Checker can be a helpful tool before clinical consultations.

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Side Effects: Not Just the Same List

Both drugs can cause dizziness, sleepiness, blurred vision, and edema. But here’s how pregabalin vs gabapentin differ:

• Gabapentin: More GI upset (nausea, constipation), and often milder sedation.
• Pregabalin: Stronger sedation, higher risk of weight gain and peripheral edema. (Cochrane Review)

⚠️ Importantly, the 2025 JAMA heart risk study now adds a new red flag: pregabalin may raise incident heart failure risk in adults 65–89, especially those with pre-existing cardiovascular disease. (JAMA Network Open)

👉 For users tracking heart health, pairing pregabalin with our BMI Calculator and Medicine Dosage Calculator can help spot sudden fluid retention or over-dosing.

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Patient Preference & Cost

Finally, let’s not forget cost when comparing pregabalin vs gabapentin:

• Gabapentin: Off-patent for years, widely available as a cheap generic—especially useful for long-term therapy.
• Pregabalin: Patents expired more recently; still costlier in many regions despite generics. In India and other low-middle income countries, pregabalin may still be priced at 2–3x gabapentin.

👉 Bottom line: For patients who need fast relief and can manage cost/side effects, pregabalin may win. For those needing affordable, steady therapy, gabapentin remains a safe bet.

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Why Heart Failure Matters in the Pregabalin vs Gabapentin Debate

When patients and doctors weigh pregabalin vs gabapentin, the new 2025 JAMA Network Open study showed pregabalin users had ~48% higher risk of developing heart failure compared to gabapentin in adults aged 65–89 (JAMA Network Open). For patients with prior cardiovascular disease, the risk jumped to nearly 85% higher.

This makes heart safety a critical factor—not just pain relief or cost—when deciding between the two drugs.

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How Pregabalin Affects the Heart

Scientists suggest that pregabalin may worsen heart function by:

• Increasing fluid retention and edema → Pregabalin is more likely to cause swelling than gabapentin (Mayo Clinic).
• Reducing vascular compliance → Experimental models show gabapentinoids may influence vascular smooth muscle tone (NIH).
• Triggering weight gain → Pregabalin patients report higher weight gain, which increases cardiac workload.

👉 For patients at risk, our BMI Calculator can help monitor sudden increases in weight—a red flag for fluid overload.

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Symptoms of Heart Failure to Watch on Pregabalin

If you are taking pregabalin, especially as an older adult, you should monitor for:

• Swelling of legs, feet, or abdomen (edema)
• Breathlessness on exertion or lying flat
• Sudden overnight weight gain (fluid build-up)
• Fatigue, dizziness, or palpitations

According to the European Medicines Agency, doctors are advised to use pregabalin cautiously in elderly patients with cardiovascular disease, precisely because of this risk.

👉 Use our Symptom Checker if you experience these issues, and share the results with your doctor immediately.

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Why Gabapentin Looks Safer for the Heart

Unlike pregabalin, gabapentin has not shown the same strength of association with heart failure in large cohorts. The 2025 JAMA study clearly noted that gabapentin users had lower incidence of new HF events, despite both drugs being gabapentinoids (JAMA Network Open).

This may be because:

• Gabapentin causes less edema and weight gain, which lowers cardiac strain.
• Its non-linear absorption might limit systemic exposure at high doses compared to pregabalin (Drugs.com).

👉 For cost-conscious and heart-sensitive patients, gabapentin may be a safer starting option, especially in seniors.

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Who Is Most at Risk on Pregabalin?

Based on the 2025 study and prior pharmacovigilance reports, the following groups should be most cautious:

• Adults 65+ with prior heart disease (strongest signal in study)
• Patients with hypertension, diabetes, or obesity
• Those already on fluid-retaining drugs (like NSAIDs or steroids)
• Elderly women—the JAMA cohort had 66.8% female participants, highlighting possible gender vulnerability.

For these patients, doctors may prefer gabapentin or alternative therapies.

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Practical Monitoring Tips

Doctors and patients can reduce risks by:

1. Starting pregabalin at the lowest effective dose and titrating slowly.
2. Monitoring weight weekly (use our Medicine Dosage Calculator to avoid accidental overdosing).
3. Checking for edema at every visit.
4. Considering baseline and follow-up echocardiograms in high-risk patients.

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Why Doctors Are Rethinking Pregabalin vs Gabapentin

The 2025 JAMA Network Open study highlighted that pregabalin raises new-onset heart failure risk by ~48% in older adults compared to gabapentin (JAMA Network Open). This is no small signal—gabapentinoids are among the most prescribed pain drugs in the world.

Cardiologists and neurologists are now urging a more cautious, individualized approach:

• Pregabalin may remain the drug of choice for fibromyalgia or when rapid pain relief is needed.
• Gabapentin is being favored more often in elderly patients with cardiovascular disease due to its safer cardiac profile.

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How Doctors Decide Between Pregabalin vs Gabapentin

When a clinician sits with a patient, they weigh several questions:

• Does the patient have heart disease or risk factors? If yes, gabapentin is safer.
• Is the pain severe and needs rapid relief? Pregabalin may still be considered, but under closer monitoring.
• What about cost? Gabapentin is almost always cheaper, which matters in long-term therapy.
• What about patient age? Over 65 = higher pregabalin risk.
• Are there alternative therapies? Sometimes SNRIs like duloxetine are safer for nerve pain in cardiac patients.

👉 Internal support: Patients can check affordability and health impact side-by-side with our Medicine Dosage Calculator.

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Switching from Pregabalin to Gabapentin Safely

Doctors sometimes need to switch a patient already on pregabalin to gabapentin. A common clinical conversion is roughly 1:6 pregabalin:gabapentin dose ratio (Pharmacy Times).

Example (not medical advice):

• Patient on 150 mg pregabalin daily → may require ~900 mg gabapentin in divided doses.

Steps followed in clinics:

1. Taper pregabalin gradually to avoid withdrawal, seizures, or rebound pain.
2. Introduce gabapentin at a low dose, then titrate up.
3. Monitor for edema, weight changes, or breathlessness during the transition.

👉 Patients can log early warning signs using our Symptom Checker to share directly with their doctor.

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Monitoring Protocols Doctors Use

To reduce risks, clinicians are now advised to:

• Do baseline weight and kidney function checks before starting pregabalin.
• Use the lowest effective pregabalin dose when alternatives are not feasible.
• Reassess patients at 2–4 weeks for edema, weight gain, or dyspnea.
• Switch to gabapentin if early heart-failure symptoms appear.
• Consider echocardiograms in high-risk elderly patients.

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Case Scenarios (Doctor’s Viewpoint)

• Case 1: 72-year-old woman with diabetes + hypertension + neuropathy
  → Doctor prescribes gabapentin first, avoids pregabalin due to CHF risk.
• Case 2: 65-year-old man with severe fibromyalgia unresponsive to gabapentin
  → Pregabalin may be tried, but at low dose, plus monthly cardiac follow-up.
• Case 3: 80-year-old woman on pregabalin develops swelling & breathlessness
  → Doctor switches to gabapentin, orders cardiac work-up, and adjusts dosage.

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Key Takeaways for Doctors and Patients

• Pregabalin vs Gabapentin is no longer just about pain relief—heart safety must be part of every decision.
• Pregabalin = faster relief, but higher heart risk in elderly.
• Gabapentin = slower relief, cheaper, safer for the heart.
• Doctors should monitor, taper, and educate patients on warning signs.

👉 To make better decisions, patients can use the AI Prescription Checker before starting or switching between these drugs.

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25 Expert FAQs on Pregabalin vs Gabapentin

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Final Verdict

When it comes to pregabalin vs gabapentin in 2025:

• Pregabalin: Faster relief, stronger efficacy in pain and fibromyalgia, but higher risk of weight gain, edema, and heart failure in seniors.
• Gabapentin: Slower onset, cheaper, and safer for the heart—making it the preferred choice for many older adults.

👉 For everyday patients:

• Use the AI Prescription Checker to see potential risks.
• Track body weight weekly with the BMI Calculator.
• Watch for swelling or breathlessness using the Symptom Checker.