Low Dose Colchicine for Secondary Prevention of Cardiovascular Disease 2 - LoDoCo2

Contribution To Literature:

The LoDoCo2 trial showed that colchicine improves CV outcomes (primarily MI and ischemia-driven revascularization) among patients with chronic coronary disease compared with placebo. However, there was a signal towards higher non-CV mortality with colchicine.

Description:

The goal of the trial was to assess the safety and efficacy of colchicine in patients with chronic coronary disease.

Study Design

Patients were randomized in a 1:1 fashion to either colchicine 0.5 mg daily or matching placebo. 

  • Total number of enrollees: 5,522
  • Duration of follow-up: 28.6 months (median)
  • Mean patient age: 66 years
  • Percentage female: 15.3%

Inclusion criteria:

  • Age 35-82 years
  • Evidence of coronary disease on invasive coronary angiography or computed tomography
  • Angiography or a coronary artery calcium score of ≥400 Agatston units on a coronary artery calcium scan
  • Clinically stable condition for ≥6 months

Exclusion criteria:

  • Moderate-to-severe renal impairment
  • Severe heart failure
  • Severe valvular heart disease
  • Known side effects from colchicine

Other salient features/characteristics:

  • History of acute coronary syndrome: 84%
  • Prior coronary revascularization: 84%
  • Single antiplatelet: 67%, dual antiplatelet: 23%, statin: 94%

Principal Findings:

The primary outcome, cardiovascular (CV) death, myocardial infarction (MI), stroke, ischemia-driven revascularization, for colchicine vs. placebo, was 6.8% vs. 9.6% (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.57-0.83, p < 0.001). 

  • MI: 3.0% vs. 4.2% (p = 0.01)
  • Ischemic stroke: 0.6% vs. 0.9% (p = 0.2)
  • Ischemia-driven revascularization: 4.9% vs. 6.4% (p = 0.01)
  • CV mortality: 0.7% vs. 0.9% (p > 0.05)

Secondary outcomes for colchicine vs. placebo: 

  • CV death, MI, stroke: 4.2% vs. 5.7% (p = 0.007)
  • All-cause mortality: 2.6% vs. 2.2% (p > 0.05)
  • Non-CV death: 0.7 vs. 0.5 events/100 patient-years (HR 1.51, 95% CI 0.99-2.31)
  • Hospitalization for pneumonia: 1.7% vs. 2.0%

Interpretation:

The results of this trial indicate that colchicine improves CV outcomes among patients with chronic coronary disease compared with placebo. Reductions were noted in MI and ischemia-driven revascularization. However, there was a signal towards higher non-CV mortality with colchicine. Etiology was unclear, but hospitalizations for infections and pneumonia were similar between the two arms.

These are interesting findings. The COLCOT trial showed a benefit in ischemic outcomes among a similar high-risk population. In that trial, there was a neutral effect on death (1.8% vs. 1.8%) and benefit was predominantly driven by a reduction in urgent revascularizations. COPS was a smaller trial in ACS patients that showed a similar benefit in revascularization, but with a significantly higher risk of non-CV mortality (5 vs. 0, p = 0.02). It is unclear if this is a true signal or a chance finding, but will need to be carefully assessed going forward. Discontinuations due to side effects are frequent with colchicine; in this trial, 15% did not undergo randomization after enrollment in the run-in phase due to side effects.

References:

Nidorf SM, Fiolet AT, Mosterd A, et al., on behalf of the LoDoCo2 Trial Investigators. Colchicine in Patients With Chronic Coronary Disease. N Engl J Med 2020;Aug 31:[Epub ahead of print].

Presented by Dr. Mark Nidorf at the European Society of Cardiology Virtual Congress, August 31, 2020.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and Arrhythmias, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: ESC Congress, ESC20, Acute Coronary Syndrome, Brain Ischemia, Colchicine, Coronary Angiography, Coronary Artery Disease, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Plaque, Atherosclerotic, Pneumonia, Secondary Prevention, Stroke


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