Effects of COLchicine on inflammation, myocardial damage and microvascular dysfunction in heart failure with Preserved Ejection Fraction – the COLpEF trial

• Published in: Archives of Cardiovascular Diseases Supplements Vol. 15; no. 1; p. 53
• Main Authors: Bourcier, L., Bellemare, M., Tremblay-Gravel, M., Henri, C., White, M., Bouabdallaoui, N.
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.01.2023
• ISSN: 1878-6480
• DOI: 10.1016/j.acvdsp.2022.10.097

Individuals with heart failure with preserved ejection fraction (HFpEF) have poor outcomes. The role of comorbidity-driven inflammation has emerged as an important mechanism involved in profibrotic activation in HFpEF, and therefore as a promising therapeutic target. Inflammation also promotes myocardial damage due to epicardial coronary artery disease (CAD), coronary microvascular dysfunction (CMD), or both, thus reinforcing its role as a potential target in HFpEF. Colchicine is an anti-inflammatory agent that has shown benefits in CAD. In HFpEF, colchicine may improve myocardial fibrosis through inhibition of inflammatory pathway implicated in myocardial damage related to CAD and/or CMD. We hypothesize that colchicine, compared to placebo, will reduce circulating levels of biomarkers of inflammation in patients with HFpEF. Secondary questions include the effects of colchicine on biomarkers of hemodynamic stress and myocardial damage, CMD and functional status. Two dosing regimens will be compared as there is no data that have validated the appropriate dose of colchicine for HF indications. COLpEF will be a randomized, blinded, multiple-dose placebo-controlled trial. The primary endpoint will be the change between baseline and 6 months in high-sensitivity C-reactive protein. Secondary objectives will be the change in: 1) NT-pro brain natriuretic peptide and high-sensitivity troponin; and 2) coronary flow reserve, a marker of CMD, assessed using adenosine-based positron emission tomography imaging. Tertiary objectives will be the change in NYHA class and six-minute walk test. A total of 426 participants will be randomly assigned to receive a 6-month course of colchicine at a dose of 0.5mg twice daily, colchicine at a dose of 0.5mg once daily or placebo. Follow-up will occur at 3 and 6 months after randomization. Patients will be randomized through an existing HFpEF collaboration across Québec (Canada). Inflammation has emerged as an important feature involved in HFpEF, and therefore as a promising therapeutic target in this setting. The COLpEF study is aimed at validating the proinflammatory profibrotic hypothesis in HFpEF using colchicine. We expect that colchicine will allow for a significant reduction in circulating markers of inflammation and myocardial damage in HFpEF. We also expect an improvement in CMD and functional status with colchicine.