Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial

Abstract An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement (TAVR). In this single-centre, double-blind, placebo-controlled, randomized trial we investigated the efficacy of colchicine to reduce a composite of new-onset atrial fibrillation or at...

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Main Authors: Christoph Ryffel, Jonas Lanz, Nicole Guntli, Daryoush Samim, Monika Fürholz, Stefan Stortecky, Daijiro Tomii, Dik Heg, Martina Boscolo Berto, Alan Arthur Peters, David Reineke, Tobias Reichlin, Christoph Gräni, Stephan Windecker, Thomas Pilgrim
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61916-6
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author Christoph Ryffel
Jonas Lanz
Nicole Guntli
Daryoush Samim
Monika Fürholz
Stefan Stortecky
Daijiro Tomii
Dik Heg
Martina Boscolo Berto
Alan Arthur Peters
David Reineke
Tobias Reichlin
Christoph Gräni
Stephan Windecker
Thomas Pilgrim
author_facet Christoph Ryffel
Jonas Lanz
Nicole Guntli
Daryoush Samim
Monika Fürholz
Stefan Stortecky
Daijiro Tomii
Dik Heg
Martina Boscolo Berto
Alan Arthur Peters
David Reineke
Tobias Reichlin
Christoph Gräni
Stephan Windecker
Thomas Pilgrim
author_sort Christoph Ryffel
collection DOAJ
description Abstract An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement (TAVR). In this single-centre, double-blind, placebo-controlled, randomized trial we investigated the efficacy of colchicine to reduce a composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker at 30 days after TAVR. Between September 21, 2021 and April 25, 2024, 120 patients with aortic stenosis undergoing TAVR (mean age 80.6 ± 5 years, 64% male) were randomly allocated to treatment with colchicine (n = 60) or placebo (n = 60). The trial was prematurely stopped due to a higher rate of stroke in the experimental group in a pre-specified interim analysis (5 [8.3%] versus 0 at maximum available follow-up, p = 0.022). In the intention-to-treat population, the primary endpoint occurred in 6 patients (10%) in the colchicine group and in 15 patients (25%) in the placebo group (risk-difference −15.0%, 95% CI −28.3 to −1.7, p = 0.031). The prespecified imaging endpoint, subclinical leaflet thrombosis, was detected in 13 of 48 patients (27%) in the colchicine group versus 26 of 48 patients (54%) in the placebo group (risk difference −27.1%. 95% CI −46.0% to −8.2%, p = 0.007). Here, we show that periprocedural treatment with colchicine may reduce the incidence of new-onset arrhythmias and subclinical leaflet thrombosis after TAVR. However, given the premature termination of the trial due to an unexpected increase in the stroke rate among patients treated with colchicine, confirmatory trials are warranted to corroborate the effect of anti-inflammatory treatment on the incidence of arrhythmias and subclinical leaflet thrombosis after TAVR. The trial was an investigator-initiated study supported by dedicated grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation. ClinicalTrials.gov Identifier: NCT04870424.
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spelling doaj-art-9403dfa8a49a46d08af3706b0be0317a2025-08-20T03:05:06ZengNature PortfolioNature Communications2041-17232025-07-0116111110.1038/s41467-025-61916-6Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trialChristoph Ryffel0Jonas Lanz1Nicole Guntli2Daryoush Samim3Monika Fürholz4Stefan Stortecky5Daijiro Tomii6Dik Heg7Martina Boscolo Berto8Alan Arthur Peters9David Reineke10Tobias Reichlin11Christoph Gräni12Stephan Windecker13Thomas Pilgrim14Department of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Clinical Research, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University HospitalDepartment of Cardiac Surgery, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernDepartment of Cardiology, Inselspital, Bern University Hospital, University of BernAbstract An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement (TAVR). In this single-centre, double-blind, placebo-controlled, randomized trial we investigated the efficacy of colchicine to reduce a composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker at 30 days after TAVR. Between September 21, 2021 and April 25, 2024, 120 patients with aortic stenosis undergoing TAVR (mean age 80.6 ± 5 years, 64% male) were randomly allocated to treatment with colchicine (n = 60) or placebo (n = 60). The trial was prematurely stopped due to a higher rate of stroke in the experimental group in a pre-specified interim analysis (5 [8.3%] versus 0 at maximum available follow-up, p = 0.022). In the intention-to-treat population, the primary endpoint occurred in 6 patients (10%) in the colchicine group and in 15 patients (25%) in the placebo group (risk-difference −15.0%, 95% CI −28.3 to −1.7, p = 0.031). The prespecified imaging endpoint, subclinical leaflet thrombosis, was detected in 13 of 48 patients (27%) in the colchicine group versus 26 of 48 patients (54%) in the placebo group (risk difference −27.1%. 95% CI −46.0% to −8.2%, p = 0.007). Here, we show that periprocedural treatment with colchicine may reduce the incidence of new-onset arrhythmias and subclinical leaflet thrombosis after TAVR. However, given the premature termination of the trial due to an unexpected increase in the stroke rate among patients treated with colchicine, confirmatory trials are warranted to corroborate the effect of anti-inflammatory treatment on the incidence of arrhythmias and subclinical leaflet thrombosis after TAVR. The trial was an investigator-initiated study supported by dedicated grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation. ClinicalTrials.gov Identifier: NCT04870424.https://doi.org/10.1038/s41467-025-61916-6
spellingShingle Christoph Ryffel
Jonas Lanz
Nicole Guntli
Daryoush Samim
Monika Fürholz
Stefan Stortecky
Daijiro Tomii
Dik Heg
Martina Boscolo Berto
Alan Arthur Peters
David Reineke
Tobias Reichlin
Christoph Gräni
Stephan Windecker
Thomas Pilgrim
Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
Nature Communications
title Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
title_full Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
title_fullStr Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
title_full_unstemmed Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
title_short Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial
title_sort colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement a double blind randomized trial
url https://doi.org/10.1038/s41467-025-61916-6
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