Highlights
- •Low-dose colchicine significantly reduces the risk of cardiovascular events.
- •Low-dose Colchicine 2 trial showed a numeric increase in non-cardiovascular deaths.
- •Long-term colchicine treatment is not associated with any specific cause of death.
- •Of note, deaths by cancer and infection were equal between colchicine and placebo.
- •These results confirm the safety of long-term use of low-dose colchicine.
Abstract
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.
Keywords
Abbreviations:
CANTOS (Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease), COLCOT (Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction), eGFR (estimated glomerular filtration rate), HR (hazard ratio), CI (confidence interval), IL (interleukin), LoDoCo2 (Low-Dose Colchicine 2)1. Introduction
Anti-inflammatory therapy reduces the risk of cardiovascular events in patients with coronary disease. [
1
, 2
, 3
] However, there are concerns that suppressing the immune response may expose patients to an increased risk of serious infections. This concern was first raised in the Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS) trial, which demonstrated that inhibiting interleukin (IL)-1β with canakinumab reduced the risk of cardiovascular events. Despite these benefits, canakinumab did not reduce all-cause mortality and was associated with an increase in neutropenia and a small increase in the number of fatal infections, raising concerns about the safety of targeting IL-1β in patients with coronary disease. [[1]
]Recently, strong evidence has emerged to support cardiovascular benefits of low-dose colchicine in coronary artery disease. [
[2]
,[3]
] Colchicine has broad anti-inflammatory effects. It is avidly taken up by leucocytes and endothelium and affects the expression of a range of interleukins including IL-1β, IL-6 and IL-18. These immunomodulating actions are believed to explain its effectiveness in the prevention of inflammatory flares in patients with gout, pericarditis, and Familial Mediterranean fever. [[4]
,[5]
]The Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction (COLCOT) and Low-Dose Colchicine 2 (LoDoCo2) trials together randomized >10,000 participants with coronary disease, with follow-up extending out to five years, demonstrating that low-dose colchicine on top of usual medical therapy reduced the composite of cardiovascular death, myocardial infarction, stroke, and coronary revascularization. [
[2]
,[3]
] In both trials, colchicine did not affect all-cause mortality. While non-cardiovascular mortality was not a pre-specified endpoint, on post hoc analysis of the LoDoCo2 trial colchicine was associated with a numeric increase in non-cardiovascular deaths. [[3]
] To adequately judge the benefit/safety ratio with the possible widespread use of colchicine for coronary disease, this observation warrants detailed examination. [[6]
] Here we report cause-specific mortality and baseline predictors of mortality.2. Methods
2.1 Study population
The LoDoCo2 trial (Australian New Zealand Clinical Trials Registry; ACTRN12614000093684) was a randomized, parallel, double-blind trial that evaluated the effect of adding colchicine 0.5 mg once daily or placebo in patients with chronic coronary disease on a background of optimal medical therapy. Randomization was performed in a 1:1 ratio with the use of a computerized algorithm, with stratification according to country. Details of the trial design are described elsewhere. [
[7]
] In brief, patients aged 35 to 82 years with proven coronary artery disease were recruited. In Australia, participants were recruited from private practices across metropolitan Perth and regional centers in Western Australia. In the Netherlands, participants were recruited from the outpatient clinics of 30 hospitals. The study excluded patients with cardiovascular events within the prior six months and those with advanced renal impairment (serum creatinine <150 mmol/l or estimated glomerular filtration rate (eGFR) <50 mL/min/1.73m2), severe heart failure, known intolerance to colchicine, and dependency, frailty, or a predicted life expectancy <5 years. All participants had proven tolerant to a 30-day trial of open label colchicine. The full list of the in- and exclusion criteria is published in the trial design paper. [[7]
]The study was conducted according to the guidelines of the 1975 Declaration of Helsinki. The trial protocol was approved by a centralized institutional review board in each participating country: Sir Charles Gairdner Group HREC, Perth, Australia (HREC No. 2013–236) and MEC-U, Nieuwegein, the Netherlands (MEC-U No. R16.027). All trial participants provided written informed consent to participate in the trial. The trial was overseen by an independent data and safety monitoring board. The trial was ended due to completion, and the primary results of the trial have previously been published. [
[3]
]2.2 Outcomes
Every six months participants presented in person to provide feedback about the status of their health. Outcomes were recorded, including admission to hospital for myocardial infarction, coronary intervention, or stroke. All correspondence related to clinical visits, hospital admissions, investigations and reports were obtained to determine and verify the occurrence of potential outcomes.
The primary efficacy outcome of the trial was the composite of cardiovascular death, myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. Secondary outcomes included death from any cause, and cardiovascular death. Non-cardiovascular death was reported as a safety outcome. All deaths were adjudicated by a by a local member of the clinical events committee, blinded to treatment allocation, by assessment of a discharge summary or clinical notes, information by treating physician or a death certificate, and, if available, an autopsy report. If the adjudicator agreed with the site investigator, the event was confirmed. If the adjudicator did not agree a second adjudicator reviewed the clinical information, and consensus was reached after deliberation.
2.3 Statistical analysis
Cause-specific mortality data were tabulated according to treatment assignment. Baseline characteristics for the randomized population, comparing participants who died with those did not, were summarized using mean ± standard deviation for quantitative data and as proportions for categorical data. A univariate analysis was used to examine predictors of all-cause death, and multivariate analyses were used to examine the predictors of all-cause, cardiovascular and non-cardiovascular death by Cox proportional hazard models.
3. Results
Between August 2014 and December 2018, the LoDoCo2 trial enrolled 5522 patients with chronic coronary artery disease, with a median follow-up of 29 months (interquartile range, 21–44), and a maximum of 63 months. Vital status was confirmed in all patients. In each trial group, 10.5% of the patients permanently discontinued trial medication. Over the course of the trial, out of 5522 randomized patients, 133 (2.4%) died during. Forty-five deaths were due to cardiovascular causes (colchicine versus placebo: 20 [0.7%] versus 25 [0.9%], hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.44–1.44), while eighty-eight deaths were due to non-cardiovascular causes (53 [1.9%] versus 35 [1.3%]; HR, 1.51; 95% CI, 0.99–2.31). Non-cardiovascular deaths were more frequent than cardiovascular deaths in both treatment groups. The majority of deaths were due to cancer (26 [0.9%] versus 22 [0.8%]), end-stage pulmonary disease (9 [0.3%] versus 4 [0.1%]), or infection (4 [0.1%] versus 4 [0.1%]). Categories of cause-specific mortality including non-cardiovascular death are listed in Table 1. Although there were more non-cardiovascular deaths in those assigned to colchicine compared with placebo, there was no significant difference in any specific cause of non-cardiovascular deaths between treatment groups. Of particular note was the finding that deaths due to the two conditions most likely to be affected by an adverse effect of colchicine on the immune system, i.e., cancer and infection, were largely identical.
Table 1Causes of death.
| Total, n = 5522 | Colchicine, n = 2762 | Placebo, n = 2760 | ||||
|---|---|---|---|---|---|---|
| n | (%) | n | (%) | n | (%) | |
| All Deaths | 133 | (2.41) | 73 | (2.64) | 60 | (2.17) |
| Cardiovascular causes of deaths | ||||||
| Sudden death | 28 | (0.51) | 11 | (0.40) | 17 | (0.62) |
| Major bleeding | 6 | (0.11) | 2 | (0.07) | 4 | (0.14) |
| Myocardial infarction | 4 | (0.07) | 2 | (0.07) | 2 | (0.07) |
| Heart failure | 2 | (0.04) | 2 | (0.07) | 0 | (0.00) |
| Stroke | 2 | (0.04) | 1 | (0.04) | 1 | (0.04) |
| Other | 3 | (0.05) | 2 | (0.07) | 1 | (0.04) |
| Non-cardiovascular causes of deaths | ||||||
| Cancer | 48 | (0.87) | 26 | (0.94) | 22 | (0.80) |
| End stage pulmonary disease | 13 | (0.24) | 9 | (0.33) | 4 | (0.14) |
| Infection | 8 | (0.14) | 4 | (0.14) | 4 | (0.14) |
| Dementia | 5 | (0.09) | 4 | (0.14) | 1 | (0.04) |
| Multiple organ failure | 5 | (0.09) | 3 | (0.11) | 2 | (0.07) |
| Accidental | 5 | (0.09) | 3 | (0.11) | 2 | (0.07) |
| Other | 3 | (0.07) | 3 | (0.11) | 0 | (0.00) |
| Unknown cause | 1 | (0.02) | 1 | (0.04) | 0 | (0.00) |
a Cerebral arteritis, myeloma, post-operative aspiration pneumonitis.
In a univariate analysis, baseline characteristics associated with an increased risk of all-cause mortality included age > 65 years, diabetes, atrial fibrillation, and prior coronary artery bypass grafting. In contrast, statin use and anti-platelet therapies were associated with a reduced risk of all-cause mortality (Table 2). Multivariable analyses demonstrated that the baseline characteristics independently associated with all-cause mortality were: age > 65 years, current smoking, prior coronary artery bypass grafting, lipid lowering therapy and anti-platelet therapy. Baseline characteristics associated with cardiovascular death were diabetes, prior coronary bypass surgery, lipid lowering therapy and anticoagulant therapy. The only baseline characteristic independently associated with a non-cardiovascular death was age > 65 years (HR, 3.65; 95% CI, 2.06–6.47; Table 3).
Table 2Univariate analyses.
| Alive, n = 5389 | All Deaths, n = 133 | Univariate analysis | |||||
|---|---|---|---|---|---|---|---|
| Characteristic | n | (%) | n | (%) | HR | (95% CI) | p-value |
| Age (mean ± SD) | 65.7 | ± 8.6 | 70.9 | ± 7.1 | |||
| ≤ 65 years | 2394 | (44) | 30 | (23) | 1 | ||
| > 65 years | 2995 | (56) | 103 | (77) | 2.44 | (1.62–3.66) | <0.01 |
| Female | 834 | (15) | 12 | (9) | 0.58 | (0.32–1.06) | 0.08 |
| Country | |||||||
| Australia | 1825 | (34) | 79 | (59) | 1 | ||
| The Netherlands | 3564 | (66) | 54 | (41) | 1.01 | (0.67–1.54) | 0.95 |
| Current smoker | 632 | (12) | 16 | (12) | 1.44 | (0.84–2.47) | 0.18 |
| Hypertension | 2732 | (51) | 76 | (57) | 1.24 | (0.88–1.76) | 0.21 |
| Diabetes | 973 | (18) | 34 | (26) | 1.56 | (1.05–2.3) | 0.03 |
| Renal function | |||||||
| Stage 1,2 | 5092 | (94) | 124 | (93) | 1 | ||
| Stage 3 | 297 | (6) | 9 | (7) | 1.85 | (0.92–3.72) | 0.08 |
| Prior ACS | 4547 | (84) | 111 | (83) | 1.05 | (0.67–1.67) | 0.82 |
| Prior coronary revascularization | 4518 | (84) | 103 | (77) | 0.85 | (0.56–1.29) | 0.45 |
| Prior CABG | 677 | (13) | 33 | (25) | 2.17 | (1.47–3.22) | <0.01 |
| Prior PCI | 4094 | (76) | 83 | (62) | 0.65 | (0.45–0.92) | 0.02 |
| Atrial Fibrillation | 623 | (12) | 26 | (20) | 1.88 | (1.22–2.89) | <0.01 |
| Gout | 430 | (8) | 16 | (12) | 1.55 | (0.92–2.62) | 0.10 |
| Antiplatelet therapy | 4919 | (91) | 112 | (84) | 0.40 | (0.25–0.65) | <0.01 |
| Dual antiplatelet therapy | 1252 | (23) | 28 | (21) | 0.81 | (0.53–1.23) | 0.32 |
| Anti-coagulant | 645 | (12) | 27 | (20) | 2.10 | (1.37–3.22) | <0.01 |
| Statin | 5067 | (94) | 121 | (91) | 0.52 | (0.29–0.95) | 0.03 |
| High dose statins | 3329 | (62) | 84 | (63) | 0.76 | (0.53–1.1) | 0.15 |
| Ezetimibe | 1051 | (20) | 22 | (17) | 1.04 | (0.65–1.65) | 0.88 |
| Lipid lowering agent | 5212 | (97) | 123 | (92) | 0.35 | (0.18–0.67) | <0.01 |
| ACE or ARB | 3862 | (72) | 98 | (74) | 1.08 | (0.74–1.6) | 0.68 |
| Beta-blocker | 3342 | (62) | 85 | (64) | 1.26 | (0.88–1.8) | 0.21 |
| Calcium channel blocker | 1210 | (22) | 34 | (26) | 1.13 | (0.76–1.66) | 0.55 |
| Treatment | |||||||
| Placebo | 2700 | (50) | 60 | (45) | 1 | ||
| Colchicine | 2689 | (50) | 73 | (55) | 1.21 | (0.86–1.71) | 0.26 |
ACE = angiotensin converting enzyme, ACS = acute coronary syndrome, ARB = angiotensin receptor blocker, CABG = coronary artery bypass grafting, CI = confidence interval, HR = hazard ratio, PCI = percutaneous coronary intervention, SD = standard deviation.
Table 3Multivariate analyses.
| All-cause death | CV death | Non-CV death | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Characteristic | HR | (95% CI) | p-value | HR | (95% CI) | p-value | HR | (95% CI) | p-value |
| Age | |||||||||
| >65 years | 2.18 | (1.43–3.32) | 0.0003 | 3.65 | (2.06–6.47) | <0.0001 | |||
| <65 years | 1 | 1 | |||||||
| Female | |||||||||
| Current smoker | 1.83 | (1.06–3.17) | |||||||
| Hypertension | |||||||||
| Diabetes | 2.96 | (1.63–5.37) | 0.0004 | ||||||
| Renal function | |||||||||
| Stage 1,2 | |||||||||
| Stage 3 | |||||||||
| Prior ACS | |||||||||
| Prior CABG | 1.84 | (1.24–2.75) | 3.09 | (1.67–5.74) | 0.0003 | ||||
| Prior PCI | |||||||||
| Antiplatelet therapy | 0.51 | (0.31–0.82) | |||||||
| Anti-coagulant | 3.27 | (1.74–6.12) | 0.0002 | ||||||
| High dose statins | |||||||||
| Ezetimibe | |||||||||
| Lipid lowering agent | 0.38 | (0.20–0.74) | 0.19 | (0.08–0.45) | 0.0002 | ||||
| ACE or ARB | |||||||||
| Beta-blocker | |||||||||
| Calcium channel blocker | |||||||||
| Treatment | |||||||||
| Placebo | |||||||||
| Colchicine | |||||||||
ACE = angiotensin converting enzyme, ACS = acute coronary syndrome, ARB = angiotensin receptor blocker, CABG = coronary artery bypass grafting, CI = confidence interval, CV = cardiovascular, HR = hazard ratio, PCI = percutaneous coronary intervention.
4. Discussion
During the LoDoCo2 trial, all-cause mortality was low, mostly related to non-cardiovascular causes in both treatment arms, and was unaffected by treatment with colchicine. Although the number of non-cardiovascular deaths was numerically higher in those assigned to colchicine, the incidence of specific causes of death, including cancer and infection, was no different in those assigned to colchicine or placebo. The proportion of cardiovascular to non-cardiovascular deaths was consistent with the number reported in the general population of non-hospitalized patients, [
[8]
] and consistent with recent reports in patients with chronic coronary disease treated with statins. [[9]
] Together, these data underscore the importance of comorbidities as major drivers of all-cause mortality in well-managed patients with chronic coronary disease. [- Fanaroff A.C.
- Roe M.T.
- Clare R.M.
- et al.
Competing risks of cardiovascular versus noncardiovascular death during long-term follow-up after acute coronary syndromes.
J. Am. Heart Assoc. 2017; 6e005840https://doi.org/10.1161/JAHA.117.005840
10
, 11
, - Wang J.W.
- Zhang Y.N.
- Sze S.K.
- et al.
Lowering low-density lipoprotein particles in plasma using dextran sulphate co-precipitates procoagulant extracellular vesicles.
Int. J. Mol. Sci. 2018; 19https://doi.org/10.3390/ijms19010094
12
]- Hochman J.S.
- Anthopolos R.
- Reynolds H.R.
- et al.
Survival after invasive or conservative management of stable coronary disease.
Circulation. 2022; https://doi.org/10.1161/CIRCULATIONAHA.122.062714
Clinical experience over the last 70 years has confirmed the safety of long-term use of colchicine at doses >0.5 mg daily in a wide range of patients with a variety of conditions. Aside from intentional overdose, colchicine has not been associated with the development of any specific disease or cause of death. [
[5]
] Tabular meta-analyses of the contemporary placebo controlled trials of long-term low-dose colchicine in patients with and without cardiovascular disease in >15,000 patients have not linked colchicine with the composite of non-cardiovascular death or any specific disease or cause of death. [13
, 14
, 15
, 16
] In ongoing future studies, it will be important to ensure that safety meta-analyses consider disease-specific causes of death rather than the composite of non-cardiovascular mortality. [[17]
]4.1 Limitations
The number of non-cardiovascular deaths in the trial was low, and the number of deaths attributed to a specific cause other than cardiovascular disease and cancer was very low, which limits power. For this reason, these data are insufficient to definitively exclude a causal link between long-term colchicine and any specific cause of death. As we did not prospectively collect an exhaustive list of comorbidities at randomization, we cannot exclude the possibility that a baseline imbalance in comorbidities in the treatment groups accounted for some of the differences in non-CV deaths.
5. Conclusions
During the LoDoCo2 trial, assignment to colchicine was not associated with an adverse effect on total deaths, nor with any specific causes of death. In particular, deaths due to cancer and infection were equivalent. 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.
Funding
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.
CRediT authorship contribution statement
Tjerk S.J. Opstal: Investigation, Visualization, Writing – original draft. Stefan M. Nidorf: Conceptualization, Investigation, Writing – original draft. Aernoud T.L. Fiolet: Investigation, Writing – review & editing. John W. Eikelboom: Conceptualization, Supervision, Writing – review & editing. Arend Mosterd: Investigation, Writing – review & editing. Willem A. Bax: Investigation, Validation, Writing – review & editing. Charley A. Budgeon: Data curation, Formal analysis, Visualization. Eelko Ronner: Resources, Investigation, Writing – review & editing. Fransisco J. Prins: Resources, Investigation, Writing – review & editing. Jan G.P. Tijssen: Methodology, Data curation, Formal analysis. Astrid Schut: Resources, Funding acquisition, Writing – review & editing. Peter L. Thompson: Supervision, Writing – review & editing. Saloua El Messaoudi: Supervision, Writing – review & editing. Jan H. Cornel: Conceptualization, Funding acquisition, Supervision, Writing – review & editing.
Declaration of Competing Interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgements
AM reports grants from Novartis, and personal fees from Amarin, Amgen, BMS, Boehringer Ingelheim, MSD, Pfizer. JWE reports consulting/honoraria support from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myer-Squibb, Daiichi-Sankyo, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Sanofi-Aventis, Servier and grants and/or in-kind support from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myer-Squibb, Glaxo-Smith-Kline, Pfizer, Janssen, Sanofi-Aventis. PLT reports grants, travel support and honoraria from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Merck, Pfizer. JHC reports membership of advisory boards with Amgen, AstraZeneca. TSJO, ATLF, SMN, CAB, WAB, ER, FJP, JGPT AS and SEM have nothing to disclose.
References
- Antiinflammatory therapy with Canakinumab for atherosclerotic disease.N. Engl. J. Med. 2017; 377: 1119-1131https://doi.org/10.1056/nejmoa1707914
- Efficacy and safety of low-dose colchicine after myocardial infarction.N. Engl. J. Med. 2019; 381: 2497-2505https://doi.org/10.1056/nejmoa1912388
- Colchicine in patients with chronic coronary disease.N. Engl. J. Med. 2020; 383: 1838-1847https://doi.org/10.1056/nejmoa2021372
- Mechanism of action of colchicine in the treatment of gout.Clin. Ther. 2014; 36: 1465-1479https://doi.org/10.1016/j.clinthera.2014.07.017
- Consensus statement regarding the efficacy and safety of long-term low-dose colchicine in gout and cardiovascular disease.Am. J. Med. 2022; 135: 32-38https://doi.org/10.1016/j.amjmed.2021.07.025
- Colchicine in ischemic heart disease: the good, the bad and the ugly.Clin. Res. Cardiol. 2021; 110: 1531-1542https://doi.org/10.1007/s00392-021-01828-9
- The effect of low-dose colchicine in patients with stable coronary artery disease: the LoDoCo2 trial rationale, design, and baseline characteristics.Am. Heart J. 2019; 218: 46-56https://doi.org/10.1016/j.ahj.2019.09.011
- Trends in causes of death among older persons in the United States.Aging Trends. 2005; 6: 1-12
- Competing risks of cardiovascular versus noncardiovascular death during long-term follow-up after acute coronary syndromes.J. Am. Heart Assoc. 2017; 6e005840https://doi.org/10.1161/JAHA.117.005840
- Death (after percutaneous coronary intervention) is no longer what it used to be.Circulation. 2014; 129: 1267-1269https://doi.org/10.1161/CIRCULATIONAHA.114.008492
- Lowering low-density lipoprotein particles in plasma using dextran sulphate co-precipitates procoagulant extracellular vesicles.Int. J. Mol. Sci. 2018; 19https://doi.org/10.3390/ijms19010094
- Survival after invasive or conservative management of stable coronary disease.Circulation. 2022; https://doi.org/10.1161/CIRCULATIONAHA.122.062714
- Colchicine for secondary prevention of cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials.Can. J. Cardiol. 2021; 37: 776-785https://doi.org/10.1016/j.cjca.2020.10.006
- Meta-analysis evaluating the utility of colchicine in secondary prevention of coronary artery disease.Am. J. Cardiol. 2021; 140: 33-38https://doi.org/10.1016/j.amjcard.2020.10.043
- Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials.Arthritis Res. Ther. 2020; 22: 1-15https://doi.org/10.1186/s13075-020-2120-7
- Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.Eur. Heart J. 2021; 42: 2765-2775https://doi.org/10.1093/eurheartj/ehab115
- Causation in epidemiology.J. Epidemiol. Community Health. 2001; 55: 905-912https://doi.org/10.1136/jech.55.12.905
Article info
Publication history
Published online: December 15, 2022
Accepted:
December 12,
2022
Received in revised form:
December 8,
2022
Received:
September 14,
2022
Footnotes
☆All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Identification
Copyright
© 2022 The Author(s). Published by Elsevier B.V.
User license
Creative Commons Attribution (CC BY 4.0) | How you can reuse 
Elsevier's open access license policy
Creative Commons Attribution (CC BY 4.0)
Permitted
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
Elsevier's open access license policy
ScienceDirect
Access this article on ScienceDirectLinked Article
- Could colchicine reduce cardiovascular events in coronary artery disease without increasing all-cause mortality: Avoid optical illusions!International Journal of CardiologyVol. 376
- PreviewCoronary artery disease remains the leading cause of death worldwide, despite advances in both pharmacological and interventional management. Inflammation is involved in atherosclerosis, both early in the formation and later triggering the rupture of a vulnerable plaque. Recently, cytokine-targeted treatment approaches have emerged as promising in the management of atherosclerotic disease. Inhibition of interleukin-1β by canakinumab reduced the rate of cardiovascular events by 15% in the CANTOS study (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) [1].
- Full-Text
- Preview
