Colchicine Demonstrates Lack of Effect on Atrial Arrhythmia Recurrence

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Colchicine 0.6 mg administered for 10 days to prevent atrial fibrillation (AF) recurrence after catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, according to new research.¹

Despite a lack of effect on atrial arrhythmia recurrence, results from the Impact of Short-Course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI) trial revealed a reduction in postablation chest pain consistent with pericarditis with the use of colchicine.

“This reduction was observed within days following catheter ablation, suggesting anti-inflammatory effects of short-term treatment with colchicine,” wrote the investigative team, led by Alexander P. Benz, MD, MSc, Population Health Research Institute, McMaster University.¹ “This finding is in line with evidence on the efficacy of colchicine in the prevention and treatment of pericarditis and postpericardiotomy syndrome following cardiac surgery.”

Catheter ablation by pulmonary vein isolation can prevent the recurrence of atrial fibrillation and has been associated with a pronounced quality of life improvement versus medical therapy. Still, high rates of atrial arrhythmia recurrence limit its use. Inflammation has been linked to the recurrence of atrial arrhythmia, reducing post-ablation inflammation is important for improved clinical outcomes.

Colchicine is a widely used anti-inflammatory agent that has been shown to reduce cardiovascular events among populations with atherothrombotic disease. In June 2023, the US Food and Drug Administration approved colchicine 0.5 mg tablets for reducing the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in those with established atherosclerotic disease or multiple risks for cardiovascular disease.²

Eligible participants in the IMPROVE-PVI trial included adults scheduled for catheter ablation (radiofrequency or cryoballoon ablation) for AF.¹ The trial eligibility criteria indicated planned pulmonary vein isolation was mandatory but allowed additional ablation of the cavotricuspid isthmus and other lesions. On the day of catheter ablation, trial participants were randomly assigned 1:1 to receive either colchicine 0.6 mg twice daily or a matching placebo 10 days after ablation.

Outcomes for the study included a goal to establish the feasibility of a large-scale trial powered for clinical outcomes, as well as clinical outcomes including a reduction in atrial arrhythmia following catheter ablation. Recurrence of atrial arrhythmia was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia detected on 14-day portable rhythm monitors and assessed by 2 cardiac electrophysiologists blinded to treatment assignment. Benz and colleagues hypothesized that a composite clinical outcome, consisting of an emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation for atrial arrhythmia, would be reduced with colchicine.

A total of 202 patients scheduled for catheter ablation for AF were enrolled between January 2020 and September 2021, with 101 patients each included in the colchicine and placebo groups. Overall, 199 patients were included in the modified intention-to-treat population (median age, 61 years) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Most of the catheter ablations (69.85%) represented a first procedure and antiarrhythmic drugs were prescribed at discharge in most (75%) patients.

Upon analysis, investigators found colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59 – 1.61]; P = .92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45 - 2.02]; P = .89). Colchicine was linked to a reduction in postablation chest pain consistent with pericarditis (4% versus 15%; HR, 0.26 [95% CI, 0.09 - 0.77]; P = .02) and an increase in diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95 - 11.53]; P <.001).

The median follow-up duration post-catheter ablation was 1.3 years. In that period, Benz and colleagues noted colchicine did not lower the risk of the composite clinical outcome of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation with colchicine (HR, 1.18 [95% CI, 0.69 - 1.99]; P = .55).

“Consistent with the lack of effect on ECG-documented atrial arrhythmia recurrence and burden of AF, colchicine did not reduce the incidence of cardioversion or repeat ablation during follow-up,” investigators wrote.¹

References

1. _{Benz AP, Amit G, Connolly SJ, et al. Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial. Circ Arrhythm Electrophysiol. Published online December 21, 2023. doi:10.1161/CIRCEP.123.012387}
2. _{Campbell, P. (2023) FDA approves colchicine tablets for reducing cardiovascular risk, HCP Live. Available at: https://www.hcplive.com/view/fda-approves-colchicine-tablets-for-reducing-cardiovascular-risk (Accessed: 08 January 2024)}