TY - JOUR
T1 - Drivers of mortality in patients with chronic coronary disease in the low-dose colchicine 2 trial
AU - Opstal, Tjerk S.J.
AU - Nidorf, Stefan M.
AU - Fiolet, Aernoud T. L.
AU - Eikelboom, John W.
AU - Mosterd, Arend
AU - Bax, Willem A.
AU - Budgeon, Charley A.
AU - Ronner, Eelko
AU - Prins, Fransisco J.
AU - Tijssen, Jan G. P.
AU - Schut, Astrid
AU - Thompson, Peter L.
AU - el Messaoudi, Saloua
AU - Cornel, Jan H.
N1 - Funding Information: In Australia, the study received seed funding from Sir Charles Gairdner Hospital (Research Advisory Committee of Sir Charles Gairdner Hospital and Osborne Park Group and Charlies Foundation for Research) and major funding from the National Health Medical Research Council of Australia (NHMRC project grant APP 1088455). Aspen Pharmacare Australia provided the colchicine and matching placebo tablets for the trial in Australia at no cost. Further support for infrastructure related to the day to day running of the trial has been provided by GenesisCare Australia. In the Netherlands, this trial was supported by the Withering Foundation the Netherlands, the Netherlands Heart Foundation, the Netherlands Organization for Health Research and Development (Grant no. 84801 5014), and a consortium of Teva, Disphar, and Tiofarma. The funders did not have any role in the design or conduct of the study, in the collection, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript. Funding Information: In Australia, the study received seed funding from Sir Charles Gairdner Hospital (Research Advisory Committee of Sir Charles Gairdner Hospital and Osborne Park Group and Charlies Foundation for Research) and major funding from the National Health Medical Research Council of Australia (NHMRC project grant APP 1088455). Aspen Pharmacare Australia provided the colchicine and matching placebo tablets for the trial in Australia at no cost. Further support for infrastructure related to the day to day running of the trial has been provided by GenesisCare Australia. In the Netherlands, this trial was supported by the Withering Foundation the Netherlands, the Netherlands Heart Foundation , the Netherlands Organization for Health Research and Development (Grant no. 84801 5014), and a consortium of Teva, Disphar, and Tiofarma. The funders did not have any role in the design or conduct of the study, in the collection, analysis, or interpretation of the data, or in the preparation, review, or approval of the manuscript. Publisher Copyright: © 2022 The Author(s)
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Background: Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial. Methods: Patients with chronic coronary disease were randomly allocated to colchicine 0.5 mg once daily or placebo on a background of optimal medical therapy. Cause-specific mortality data were analysed, stratified by treatment status. Multivariate analyses were performed to examine the predictors of mortality as well as cardiovascular and non-cardiovascular death. Results: After a median 28.6 months follow-up, 133 out of 5522 participants (2.4%) died. Forty-five deaths were cardiovascular (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], HR, 0.80; 95% CI, 0.44–1.44), while eighty-eight deaths were non-cardiovascular (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99–2.31). Forty-eight deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), thirteen end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), eight infection (4 [0.1%] versus 4 [0.1%]), five dementia (4 [0.1%] versus 1 [0.0%]) and five related multiple organ failure (3 [0.1%] versus 2 [0.1%]). Multivariable analysis demonstrated age > 65 years was the only independent baseline characteristic associated with non-cardiovascular death (HR, 3.65; 95% CI, 2.06–6.47). Conclusions: During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on any specific causes of death. Most deaths were related to non-cardiovascular causes, underscoring the importance of comorbidities as drivers of all-cause mortality in patients with chronic coronary disease.
AB - Background: Low-dose colchicine significantly reduces the risk of cardiovascular events in patients with chronic coronary disease. An increase of non-cardiovascular death raised concerns about its safety. This study reports cause-specific mortality and baseline predictors of mortality in the Low-Dose Colchicine 2 (LoDoCo2) trial. Methods: Patients with chronic coronary disease were randomly allocated to colchicine 0.5 mg once daily or placebo on a background of optimal medical therapy. Cause-specific mortality data were analysed, stratified by treatment status. Multivariate analyses were performed to examine the predictors of mortality as well as cardiovascular and non-cardiovascular death. Results: After a median 28.6 months follow-up, 133 out of 5522 participants (2.4%) died. Forty-five deaths were cardiovascular (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], HR, 0.80; 95% CI, 0.44–1.44), while eighty-eight deaths were non-cardiovascular (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99–2.31). Forty-eight deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), thirteen end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), eight infection (4 [0.1%] versus 4 [0.1%]), five dementia (4 [0.1%] versus 1 [0.0%]) and five related multiple organ failure (3 [0.1%] versus 2 [0.1%]). Multivariable analysis demonstrated age > 65 years was the only independent baseline characteristic associated with non-cardiovascular death (HR, 3.65; 95% CI, 2.06–6.47). Conclusions: During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on any specific causes of death. Most deaths were related to non-cardiovascular causes, underscoring the importance of comorbidities as drivers of all-cause mortality in patients with chronic coronary disease.
KW - Anti-inflammatory agents
KW - Atherosclerosis
KW - Cardiovascular inflammation
KW - Death
KW - Secondary prevention
UR - http://www.scopus.com/inward/record.url?scp=85144749763&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ijcard.2022.12.026
DO - https://doi.org/10.1016/j.ijcard.2022.12.026
M3 - Article
C2 - 36529304
SN - 0167-5273
VL - 372
SP - 1
EP - 5
JO - International journal of cardiology
JF - International journal of cardiology
ER -