Pregabalin vs Gabapentin Heart Failure Risk: New Evidence Every Pain Physician Must Know

Introduction

👉 Could one of our most trusted pain medicines be quietly raising the risk of heart failure in elderly patients?

Gabapentinoids—pregabalin and gabapentin—are widely prescribed as non-opioid alternatives for chronic pain. Their popularity has grown as safer choices than opioids, especially in elderly patients. However, emerging research warns of cardiovascular safety concerns, particularly with pregabalin.

What is the pregabalin vs gabapentin heart failure risk in older adults with chronic pain?

Park EE, Daniel LL, Dickson AL, et al. Initiation of Pregabalin vs Gabapentin and Development of Heart Failure. JAMA Netw Open. 2025;8(8):e2524451. doi:10.1001/jamanetworkopen.2025.24451 park_2025_oi_250698_1753385526.…

This research, published in JAMA Network Open, represents one of the largest real-world analyses of gabapentinoids in elderly patients, highlighting new cardiovascular safety concerns.

Study Overview: Pregabalin vs Gabapentin in Chronic Pain

• Design: Retrospective cohort, target trial emulation

• Population: 246,237 Medicare patients (65–89 years) with chronic noncancer pain

• Comparison: New users of pregabalin (18,622) vs gabapentin (227,615)

• Outcome: Heart failure (HF) hospitalization, ED visits, outpatient HF diagnosis, and mortality

• Adjustment: 231 covariates controlled using propensity score weighting

This robust methodology strengthens the reliability of the results and ensures clinical applicability.

This large retrospective cohort study examined 246,237 Medicare beneficiaries aged 65 to 89 years with chronic noncancer pain who initiated therapy with either pregabalin (18,622 patients) or gabapentin (227,615 patients) between January 2015 and December 2018. To ensure the validity of outcomes, individuals with pre-existing heart failure, terminal illnesses, or prolonged institutional care were excluded, thereby focusing on truly incident heart failure events. The investigators employed a target trial emulation design—an advanced method that mimics the rigor of a randomized clinical trial—while accounting for 231 baseline covariates related to demographics, comorbidities, prior medication use, and health care utilization, using inverse probability of treatment weighting to minimize confounding. Over 114,113 person-years of follow-up, a total of 1,470 new heart failure cases were recorded. The incidence rate was 18.2 per 1000 person-years in the pregabalin group versus 12.5 per 1000 person-years in the gabapentin group, yielding an adjusted hazard ratio (AHR) of 1.48 (95% CI, 1.19–1.77). Notably, the risk elevation was more pronounced in patients with established cardiovascular disease at baseline, in whom pregabalin use nearly doubled the risk (AHR 1.85). Subgroup analyses showed the association was strongest in White patients and in women, whereas no significant effect was found in racial/ethnic minority groups or men. Secondary outcomes further supported the signal: outpatient diagnoses of heart failure were significantly higher with pregabalin (AHR 1.27), and combined inpatient/outpatient analyses yielded similar trends. Importantly, there was no significant difference in all-cause mortality between the two groups (AHR 1.26), and negative control analyses using hip fracture as an outcome showed no spurious associations, strengthening the credibility of the findings. Overall, this rigorously designed study provides compelling real-world evidence that pregabalin, compared with gabapentin, carries a significantly higher risk of incident heart failure in elderly patients with chronic pain, particularly those with cardiovascular comorbidities

Important Findings on Heart Failure Risk

Pregabalin Associated With Higher HF Risk

• HF incidence:

  • Pregabalin: 18.2 per 1000 person-years

  • Gabapentin: 12.5 per 1000 person-years

• Adjusted Hazard Ratio (AHR): 1.48 (95% CI, 1.19–1.77)park_2025_oi_250698_1753385526.…

Stronger Effect in Patients With Cardiovascular Disease

• AHR: 1.85 (95% CI, 1.38–2.47)

• Confirms that pregabalin should be prescribed with extreme caution in patients with existing cardiovascular comorbidities.

Secondary Outcomes

• Outpatient HF diagnosis is higher with pregabalin (AHR: 1.27; 95% CI, 1.02–1.58).

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

Clinical Implications for Pain Physicians

Choosing Between Pregabalin and Gabapentin

This evidence suggests that gabapentin is the safer option for elderly patients with cardiovascular risk. While pregabalin may offer stronger analgesic potency in neuropathic pain and fibromyalgia, the pregabalin vs gabapentin heart failure risk comparison tips the scale in favor of gabapentin in high-risk populations.

Practical Recommendations

• Risk–Benefit Assessment: Evaluate cardiovascular history before prescribing pregabalin.

• Patient Monitoring: Watch for HF symptoms (edema, dyspnea, fatigue).

• Collaborative Care: Involve cardiologists for elderly or high-risk patients.

• Patient Education: Clearly explain HF risks and early warning signs.

Limitations of the Study

• Restricted to Medicare beneficiaries aged 65–89 years.

• Majority were White and female, limiting generalizability.

• Observational design, although strengthened by target trial emulation, cannot fully rule out residual confounding.

Conclusion

The latest evidence confirms that pregabalin carries a significantly higher risk of heart failure compared to gabapentin in elderly patients with chronic pain.

For pain physicians, the clinical message is clear:👉 When treating elderly patients with cardiovascular risk, gabapentin should be the preferred first-line choice.

Takeaway: Pregabalin vs Gabapentin Heart Failure Risk is no longer a theoretical concern—it is a critical clinical decision for safer pain management.

FAQ - Pregabalin vs Gabapentin Heart Failure Risk in the Elderly

Q1: Which is safer for elderly patients—pregabalin or gabapentin?

A: Evidence shows gabapentin is associated with lower heart failure risk, making it safer for elderly patients with cardiovascular comorbidities.

Q2: Can pregabalin cause heart problems?

A: Yes, large cohort studies show pregabalin is linked to a higher incidence of new-onset heart failure, particularly in high-risk elderly patients.

Q3: Should gabapentinoids replace opioids in chronic pain management?

A: Gabapentinoids are often preferred over opioids, but drug choice must consider comorbidities. Pregabalin’s HF risk means gabapentin may be the safer option in many older patients.

📖 Reference:Park EE, Daniel LL, Dickson AL, et al. Initiation of Pregabalin vs Gabapentin and Development of Heart Failure. JAMA Netw Open. 2025;8(8):e2524451. doi:10.1001/jamanetworkopen.2025.24451 park_2025_oi_250698_1753385526.…

About Asian Pain Academy

The Asian Pain Academy (APA) is a premier institute dedicated to advancing structured education in Pain Medicine across Asia and beyond. Founded by leading experts, APA offers 6-month and 1-year fellowship programs blending online modules, interactive case discussions, and intensive hands-on workshops in Kolkata. With a strong global faculty network and alumni from multiple countries, APA is committed to training the next generation of pain physicians through evidence-based, practical, and patient-focused education.

About the Author

Dr. Debjyoti Dutta, MD, FIPP, FIAPM, is a leading Pain Medicine consultant based in Kolkata. He heads Samobathi Pain Clinic, is senior faculty at Fortis Hospital Kolkata, and co-founder of the Asian Pain Academy. With expertise in ultrasound- and fluoroscopy-guided interventions, he is deeply committed to advancing structured pain education and evidence-based patient care across Asia.