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.
The goal of the trial was to assess the safety and efficacy of colchicine in patients with chronic coronary disease.
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%
- 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
- 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%
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%
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.
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
< Back to Listings