While colchicine shows promise in mitigating inflammation-driven complications after transcatheter aortic valve replacement (TAVR), researchers in the Co-STAR trial urge a “cautious, tailored approach” to its use due to associated stroke risks. The warning comes after findings were presented by Thomas Pilgrim, MD, of the University Hospital of Bern, Switzerland, on Tuesday at the Transcatheter Cardiovascular Therapeutics (TCT) 2024 conference in Washington, DC, in which the trial was halted due to the heightened stroke risk. This occurred despite findings from the double-blind, randomized, controlled trial that pointed to colchicine’s ability to reduce new-onset atrial fibrillation (NOAF) and subclinical leaflet thrombosis. “Treatment with colchicine was associated with a lower risk of the primary composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a PPM at 30 days,” said Dr. Pilgrim. “The inflammatory pathway offers a potential therapeutic target to mitigate cardiac arrhythmias and subclinical leaflet thrombosis after TAVR.” Main findings Results from the trial, which enrolled 120 patients, found a statistically significant difference in stroke incidence between the colchicine and placebo groups specifically, the stroke rate difference reached 8.2% (95% confidence interval [CI] 1.12 to 15.08, p=0.022) in favor of the placebo group. The value was deemed significant enough to prematurely terminate patient recruitment following the recommendation of the Data Safety Monitoring Board (DSMB) after crossing the pre-specified stopping boundary for stroke. Further findings of the Colchicine in Patients with Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR) trial revealed the colchicine group experienced a lower rate of prosthetic valve leaflet thickening and >50% reduced motion or thickening at 30 days compared to the placebo group (p=0.007). Library of evidence Previous studies have suggested an inflammatory environment increased the risk of cardiac arrhythmias. One particular review of note concluded that colchicine demonstrated superior efficacy versus usual care for prevention of atrial fibrillation after cardiac surgery with the treatment also associated with shorter hospital stays. Further research has suggested that an inflammatory response may be involved in the development of new-onset atrial fibrillation after TAVR. Mechanical trauma of the transcatheter heart valve (THV) induces localized inflammation and tissue oedema that may contribute to the development of transient AV-block. Histopathological examination of explanted prosthetic THV identified inflammation and endothelial dysfunction as potential drivers of leaflet thrombosis. Study methodology Participants in the Co-STAR trial were adults over 65 with severe symptomatic aortic stenosis and eligible for TAVR. A total of 120 patients were randomly assigned to either a colchicine (n=60; 61.7% male) or placebo group (n=60; 66.7% male) in a 1:1 ratio. The colchicine group received an initial dose of 1mg the day before TAVR and another dose on the day of the procedure, followed by a 0.5 mg daily dose for 12 days. Patients underwent continuous cardiac rhythm monitoring and electrocardiograms to assess for NOAF and conduction disturbances, with additional 4D-computed tomography (4D-CCTA) used to evaluate leaflet motion and thickening. The primary endpoint was new-onset atrial fibrillation or new PPM implantation at 30 days. Image Caption: Thomas Pilgrim, MD, speaks during a news conference Tuesday at the Transcatheter Cardiovascular Therapeutics (TCT) conference in Washington, DC. Image Credit: Bailey G. Salimes/CRTonline.org