Colchicine in acutely decompensated heart failure: the COLICA trial

Abstract

Background and aims: Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF.

Methods: This multicenter, randomized, double-blind, and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 h of presentation to receive either colchicine or placebo, with loading dose of 2 mg, followed by 0.5 mg every 12 h for 8 weeks.

Results: A total of 278 patients [median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4262 pg/mL] were randomized to colchicine (n = 141) or placebo (n = 137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group [-62.2%, 95% confidence interval (CI) -68.9% to -54.2%] and the placebo group (-62.1%, 95% CI -68.6% to -54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (P < .001) for C-reactive protein and 0.72 (P = .019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, P = .698); however, the need for intravenous furosemide during follow-up was lower with colchicine (P = .043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%).

Conclusions: Colchicine was safe and effective in reducing inflammation in patients with AHF; however, colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events.

Keywords: Acute; Colchicine; Heart failure; Inflammation; Randomized controlled trial.

Structured Graphical Abstract

In this randomized, double-blind, placebo-controlled trial enrolling 278 patients within 24 h of presentation with AHF, colchicine was safe and effective in reducing inflammation compared to placebo, but it had comparable effects on reducing NT-proBNP levels and preventing new WHF events. AHF, acute heart failure; CI, confidence interval; CRP, C-reactive protein; HR, hazard ratio; IL-6, interleukin-6; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; WHF, worsening heart failure.

Figure 1

Consort diagram of the COLICA trial: screening, randomization, and follow-up

Figure 2

Change in NT-proBNP concentration

Figure 3

Change in inflammatory markers: C-reactive protein (CRP) and interleukin-6 (IL6)

Figure 4

Change in guideline-directed medications according to left ventricular ejection fraction phenotype