Dr. Selim Süleyman Sert

Name of the study:
Colchicine for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement (Co-STAR): a Randomized-controlled Trial

Published Congress: TCT 2024

Link: https://www.tctmd.com/slide/colchicine-patients-aortic-stenosis-undergoing-transcatheter-aortic-valve-replacement-double

Introduction:
Transcatheter aortic valve implantation (TAVI) has increasingly become an alternative to surgical aortic valve replacement for patients with severe aortic stenosis. The development of transcatheter valve technology and the growing experience of physicians have led to a significant reduction in postoperative complications such as stroke, vascular complications, and bleeding. However, conduction system disorders, such as atrioventricular block and new-onset atrial fibrillation, are observed in nearly half of the patients.

Colchicine, an approved active substance for treating acute gout attacks, pericarditis, and familial Mediterranean fever, has also been shown to be safe and effective in preventing atrial fibrillation after cardiac surgery. Due to its anti-inflammatory effects, colchicine has been included with a class 2A recommendation in the ESC 2024 guidelines for chronic coronary syndromes. In addition to this effect, by inhibiting platelet activation and reducing endothelial dysfunction, colchicine may help prevent the development of atrial fibrillation and atrioventricular conduction defects, thereby reducing the need for permanent pacemaker implantation after TAVI, while also supporting valve function.

Objective:
The Co-STAR study aimed to investigate the effects of colchicine, which has a wide range of indications, in preventing atrial fibrillation and conduction defects leading to the need for permanent pacemakers after transcatheter aortic valve implantation, as well as its role in reducing prosthetic valve leaflet dysfunction that may occur post-procedure.

Methods:
The Co-STAR study evaluated a total of 120 selected patients who presented with severe aortic stenosis and were deemed suitable for TAVI between September 2021 and April 2024. Conducted in Switzerland, this study was randomized, double-blind, and placebo-controlled. After TAVI, patients were randomly assigned to colchicine or placebo groups in a 1:1 ratio for 30 days. Participants included those aged over 65, with symptomatic severe aortic stenosis (aortic valve area (AVA) ? 1.0 cm² or indexed AVA < 0.6 cm²/m²), and those considered suitable for transfemoral TAVI by the cardiac team. Major exclusion criteria included patients with a life expectancy of less than one year regardless of valve disease, those without sinus rhythm on ECG at admission, patients with permanent pacemakers or implantable cardioverter defibrillators, and those with any planned cardiac intervention within 7 days before TAVI, simultaneously with TAVI, or within 30 days following TAVI.

Results:
The enrolled patients averaged 80 years old in both groups, with a predominance of female patients. The STS score was 2.7±1.6 in the colchicine group and 2.4±1.4 in the placebo group. In the colchicine group, 37 patients (62.7%) received balloon-expandable valves, while 22 patients (37.3%) received self-expanding valves; in the placebo group, 41 patients (70.7%) received balloon-expandable valves, and 17 patients (29.3%) received self-expanding valves. Regarding new-onset atrial fibrillation, it was observed in 5% of the colchicine group and 6.7% of the placebo group (p=0.697). The need for a new pacemaker was 8.3% in the colchicine group and 18.3% in the placebo group (p=0.107). Evaluation by four-dimensional cardiac computed tomography angiography showed a decrease in mobility of more than 50% in one or more prosthetic valve leaflets in the colchicine group (8.3%) compared to the other group (12.5%, p=0.504). For leaflet thickening, the colchicine group showed 27.1%, while the other group had 54.2% (p=0.007). In terms of 30-day clinical outcomes, all-cause mortality, myocardial infarction, acute kidney injury, and VARC-3 classified type ?1 bleeding were 0%, 0%, 5%, and 6.7% in the colchicine group, and 1.7%, 1.7%, 8.3%, and 3.3% in the placebo group (p=0.315, p=0.315, p=0.464, p=0.402). The stroke rate was 5% in the colchicine group and was not observed in the placebo group (p=0.079).

Conclusions:
The Co-STAR study, which started on September 21, 2021, and was planned to end on June 30, 2026, was halted due to a higher stroke rate in the colchicine group. However, the 30-day evaluation showed that new-onset atrial fibrillation and the need for a new pacemaker due to atrioventricular conduction defects were less frequent in the colchicine group. Additionally, a reduction in the movement and thickening of one or more prosthetic valve leaflets was less common in the colchicine group within 30 days.

Comment:
Inflammation plays a significant role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents can improve cardiovascular outcomes. Colchicine primarily exerts its anti-inflammatory effect by inhibiting microtubule assembly. The systems inhibited by colchicine include endothelial cell dysfunction and inflammation, smooth muscle cell proliferation and migration, macrophage chemotaxis, and platelet activation. Considering its wide range of indications, low cost, and tolerable side effect profile, colchicine appears to be a potentially beneficial oral cardiovascular treatment targeting the inflammatory system. The data obtained from the Co-STAR study supports these benefits of colchicine, demonstrating a reduction in complications and adverse outcomes observed after TAVI. Indeed, the stroke rate in the colchicine group was among the limiting factors of the study, leading to its cessation.