Familiar Anti-Inflammatory Felled by Strokes in TAVR Trial

 

 Ask your doctor to come up with EXACT PROTOCOLS ON COLCHICINE USE! Can't do that; you DON'T have a functioning stroke doctor or hospital!

'No Hint of Benefit' in Large Colchicine Trial  November 2024

Colchicine prevents rise in total plaque volume for patients with stable CAD April 2025

colchicine (26 posts to December 2011)

I bet your incompetent doctor and hospital DID NOTHING WITH THIS EARLIER RESEARCH! That's why they are incompetent! DOING NOTHING!

Familiar Anti-Inflammatory Felled by Strokes in TAVR Trial

Colchicine showed some favorable results reducing new-onset arrhythmias after TAVR

Key Takeaways

• The Co-STAR trial tested the performance of colchicine in preventing new-onset arrhythmias and subclinical leaflet thrombosis after TAVR.
• The choice of periprocedural treatment with colchicine was related to its targeting of the inflammatory pathway of cardiac arrhythmias.
• Colchicine showed a reduction in rhythm disturbances, albeit with excess strokes.

The inflammation suppressant colchicine could show more promise in transcatheter aortic valve replacement (TAVR) -- if not for excess strokes, as seen in one small randomized study.

In the Co-STAR double-blind trial, periprocedural treatment with colchicine resulted in favorable 30-day results indicative of reduced new-onset arrhythmias relative to placebo:

• Composite of new-onset atrial fibrillation (Afib) or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker: 10% with colchicine vs 25% with placebo (P=0.031)
• New-onset Afib alone: 5.0% vs 6.7%
• Conduction disturbances requiring permanent pacemaker: 8.3% vs 18.3%

Imaging also showed less post-TAVR subclinical leaflet thrombosis after a colchicine regimen (27% vs 54%, P=0.007), according to Thomas Pilgrim, MD, of Bern University Hospital in Switzerland, and colleagues.

However, the trial was prematurely stopped on account of strokes: three strokes (5.0%) in the colchicine group and none in the placebo group at 30 days, reaching five strokes (8.3%) with colchicine at maximal follow-up (vs 0, P=0.022), according to the Co-STAR report published in Nature Communications.

"As the study was prematurely stopped and the event rates of the primary outcome were lower than anticipated, the trial was underpowered, the observed treatment effect may be overestimated and chance findings cannot be excluded," Pilgrim's group cautioned.

Colchicine, derived from the autumn crocus plant used medicinally for thousands of years in Egypt, is an anti-inflammatory available generically. Name-brand colchicine (Lodoco) was FDA approved for cardiovascular prevention in 2023.

Pilgrim told MedPage Today that he was not aware of any established mechanism that would link colchicine treatment to an increased risk of stroke -- in fact, colchicine was previously tied to a reduced stroke risk in people with coronary artery disease.

"In our study, two of the five strokes occurred well after the completion of colchicine therapy, and one was directly related to the TAVR procedure itself," he noted.

Study authors reason that inflammation is still worth pursuing as a therapeutic target in TAVR, a concept bolstered by previous successes of colchicine in cardiac surgery.

"The etiopathology of TAVR-related arrhythmias is a complex interplay of local and systemic factors in which inflammatory processes are considered to be an important trigger. A systemic inflammatory response syndrome peaking between 24 and 48 hours after TAVR has been documented in 39-56% of patients, and may be causal in the development of atrial fibrillation," they wrote.

"Beyond colchicine, other anti-inflammatory agents, such as monoclonal antibodies targeting interleukin-1β or interleukin-6, may also be investigated in this context," Pilgrim said.

Co-STAR was a single-center trial that randomized TAVR patients to colchicine or placebo from 2021 to 2024. Investigators managed to enroll 120 out of 200 anticipated participants with severe aortic stenosis before the trial was stopped early. Eligible candidates were people with no history of Afib or permanent pacemakers or severe renal failure.

Per study protocol, colchicine treatment was initiated with a loading dose of 1 mg the day before TAVR and the day of the intervention, followed by a maintenance dose of 0.5 mg once daily for 12 days after TAVR.

The study cohort averaged age 80.6 years and was 64% men, with mean Society of Thoracic Surgeons predicted mortality reaching 2.5%.

Two in three participants got TAVR with balloon-expandable devices and the remainder received self-expanding devices. Factors known to be associated with the occurrence of atrioventricular block after TAVR (e.g., pre-existing right bundle branch block, prosthetic valve design, oversizing, and postdilatation) were well balanced between the two treatment groups, according to Pilgrim and colleagues.

All patients were monitored during hospitalization and got continuous electrocardiogram holter monitoring up to 7 days postdischarge. The mean duration of continuous rhythm monitoring was 10 days in the colchicine group, significantly longer than the 8.5 days in the placebo group.

For the imaging endpoint, 48 people in each group underwent a single coronary CT angiography at a mean 37 days after TAVR. Subclinical leaflet thrombosis was defined as a case of at least one leaflet with >50% motion reduction or thickening.

"It is possible, that colchicine does not prevent but rather defers the occurrence of subclinical leaflet thrombosis. Serial imaging would be required to rule out a catch-up effect of thrombus formation," Pilgrim's group acknowledged.

What's more, the clinical significance of post-TAVR leaflet thrombosis itself is unclear, as many cases have been observed to resolve on their own.

Disclosures

The study was supported by grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation.

Pilgrim reported research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Swiss Polar Institute, the Bangerter-Rhyner Foundation, the Mach-Gaensslen Foundation, and the Monsol Foundation; research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATsens; and speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and HighLife.

Co-authors reported multiple relationships with industry.

Primary Source

Nature Communications

Source Reference: Ryffel C, et al "Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial" Nat Commun 2025; DOI: 10.1038/s41467-025-61916-6.