Does Pregabalin Cause Atrial Fibrillation?
Pregabalin is associated with an increased risk of atrial fibrillation, particularly in elderly patients and those with pre-existing cardiovascular disease, though this risk is not mentioned in the FDA label and remains underrecognized in clinical practice.
Evidence for the Association
The FDA label for pregabalin does not list atrial fibrillation as a known adverse effect 111. However, emerging research evidence demonstrates a concerning association:
Population-Based Studies Show Increased Risk
A 2018 population-based cohort study in elderly patients (≥65 years) found that pregabalin was associated with a 2.79-fold increased risk (95% CI 1.05-7.40) of initiating treatment for atrial fibrillation compared to opiate analgesics 2. The incidence was 8.6 per 1000 patients with pregabalin versus 3.1 per 1000 with opiates, and this risk increased with higher doses 2.
Supraventricular Arrhythmias as a Precursor
The 2020 Multi-Ethnic Study of Atherosclerosis (MESA) found that gabapentinoid use (including pregabalin) was associated with:
- 84% greater frequency of premature atrial contractions (95% CI 25%-171%)
- 44% greater number of runs of supraventricular tachycardia (95% CI 3%-100%)
These supraventricular ectopic beats are known triggers for atrial fibrillation 3.
Clinical Context and Mechanism
While the exact mechanism remains unclear, pregabalin may induce tachycardia and atrial arrhythmias in predisposed patients 4. The 2024 narrative review on drug-induced atrial fibrillation emphasizes that drug-induced AF (DIAF) is an underrecognized and forgotten adverse effect that deserves more clinical attention 555.
Risk Stratification
Highest risk patients include:
- Elderly patients (≥65 years)
- Those with pre-existing cardiovascular disease
- Patients with history of paroxysmal atrial fibrillation
- Those on higher pregabalin doses
- Patients on polypharmacy
Important Caveats
Heart Failure vs. Atrial Fibrillation
A 2024 study found pregabalin increased heart failure hospitalizations (AHR 1.48,95% CI 1.19-1.77) compared to gabapentin 6, while a separate 2024 study found no increased risk of heart failure exacerbation in patients with pre-existing heart failure 7. These findings suggest pregabalin may precipitate new cardiac events rather than worsening stable disease.
Most Cases Are Paroxysmal
Drug-induced atrial fibrillation is typically paroxysmal and may resolve spontaneously after drug discontinuation 55. However, some cases persist and require cardioversion.
Clinical Recommendations
When prescribing pregabalin:
- Screen for history of atrial fibrillation or cardiovascular disease
- Consider baseline ECG in elderly patients or those with cardiac risk factors
- Start at the lowest effective dose, especially in high-risk patients
- Monitor for palpitations, irregular pulse, or new-onset dyspnea
- Maintain high index of suspicion for new-onset AF in the first weeks of therapy
- If AF develops, consider pregabalin as a potential culprit and evaluate for discontinuation
If atrial fibrillation develops:
- Assess temporal relationship to pregabalin initiation
- Consider discontinuation if other causes excluded
- Manage AF according to standard guidelines (anticoagulation, rate/rhythm control) 89
- Monitor for spontaneous resolution after drug withdrawal
The evidence suggests this is a real but underappreciated risk that warrants clinical vigilance, particularly in vulnerable populations.