Nicholas Burney                                                                                             CAT#1

Clinical Scenario: An 72 year old male with a history of cardiac stent placement and coronary artery disease presents with acute chest pain. EKG reveals an NSTEMI and he is transferred to the emergency room.

Search Question:

Can colchicine be effective in preventing future cardiac events?

Question Type: What kind of question is this?

Treatment 

Assuming that the highest level of evidence to answer your question, will be meta-analysis or systematic review, what other types of study might you include if these are not available (or if there is a much more current study of another type)? Please explain your choices.

I would search for randomized trials comparing colchicine and placebo, or prospective studies where colchicine was administered and observe if the resulting incidence of cardiac events was similar to that of the general population.

PICO search terms:

P	I	C	O
Coronary Artery Disease	Colchicine	Placebo	Prevention of cardiac events
CAD		Standard medical therapy	Reduction of inflammation
		No colchicine

Search tools and strategy used:

Please indicate what data bases/tools you used, provide a list of the terms you searched together in each tool, and how many articles were returned using those terms and filters.

Explain how you narrow your choices to the few selected articles.

PubMed

Search: Colchicine Cardiac – 1014

Filters: 10 years, meta-analysis, Systematic Review, MEDLINE – 26

Search: Colchicine ACS– 51

Filters: 10 years, meta-analysis, Systematic Review, MEDLINE – 2

Cochrane

Search: Colchicine Cardiac  – 2

Filters: 10 years –  2

Google scholar:

Search: Colchicine ACS meta analysis  – 2,160

Filters:  10 years: 2,070

I chose a mix of meta-analyses and systematic reviews for this CAT, as they demonstrate the highest level of evidence. I also tried to choose articles that followed patients for at least 3 months or more, to determine if colchicine maintained longer-term efficacy in prevention of cardiac events. The main outcome I was interested was in the prevention of future cardiac events in patients that had already had a myocardial infarction or a stent placement. These cardiac events include stroke, MI, urgent revascularization, or stent placement.

Results found:

1. Samuel, Michelle et al. “Colchicine for Secondary Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.” The Canadian journal of cardiology vol. 37,5 (2021): 776-785. doi:10.1016/j.cjca.2020.10.006

Type of Article: Meta-analysis

Background: Reduction of inflammation with colchicine has emerged as a therapeutic option for secondary prevention of cardiovascular disease (CVD) in patients with coronary artery disease (CAD). Our objective was to consolidate evidence from randomized controlled trials (RCTs) evaluating the efficacy and safety of low-dose colchicine for secondary prevention of CVD among patients with CAD on standard medical therapy.

Methods: RCTs comparing the incidence of cardiovascular (CV) events between patients with clinically manifest CAD randomized to colchicine vs placebo (or no colchicine) were included. The primary composite efficacy endpoint included CV mortality, myocardial infarction (MI), ischemic stroke, and urgent coronary revascularization. The DerSimonian and Laird random-effects model was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Four RCTs, with a pooled sample size of 11,594 patients, were included (colchicine n = 5774; placebo/no colchicine n = 5820). Included RCTs studied populations with stable CAD (N = 2) and acute coronary syndrome (N = 2). Compared with placebo or no colchicine, colchicine was associated with a statistically significant reduction in the incidence of the primary composite endpoint (pooled HR, 0.68; 95% CI, 0.54-0.81; I2 = 37.7%). The reduction in CV events among patients randomized to colchicine was driven by statistically significant reductions in MIs, ischemic strokes, and urgent coronary revascularizations (P < 0.05 for all) and was relatively consistent among subgroups. The incidence of safety outcomes did not differ between groups (P > 0.05).

Conclusions: In secondary prevention of CV events, the addition of low-dose colchicine to standard medical therapy reduces the incidence of major CV events-except CV mortality-when compared with standard medical therapy alone.

•  Hemkens, Lars G et al. “Colchicine for prevention of cardiovascular events.” The Cochrane database of systematic reviews vol. 2016,1 CD011047. 27 Jan. 2016, doi:10.1002/14651858.CD011047.pub2

Type of Article: Systematic Review

Background

Colchicine is an anti‐inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations.

Objectives

To evaluate potential cardiovascular benefits and harms of a continuous long‐term treatment with colchicine in any population, and specifically in people with high cardiovascular risk.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data.

Selection criteria

Randomised controlled trials (parallel‐group or cluster design or first phases of cross‐over studies) comparing colchicine over at least six months versus any control in any adult population.

Data collection and analysis

Primary outcomes were all‐cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non‐scheduled hospitalisations, and non‐scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. .

Main results

We included 39 randomised parallel‐group trials with 4992 participants. Colchicine had no effect on all‐cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I² = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I² = 45%; very low quality of evidence) but gastrointestinal intolerance was increased (RR 1.83, 95% CI 1.03 to 3.26; participants = 1258; studies = 11; I² = 74%; low quality of evidence). Colchicine showed no effect on heart failure (RR 0.62, 95% CI 0.10 to 3.88; participants = 462; studies = 3; I² = 45%; low quality of evidence) and no effect on stroke (RR 0.38, 95% CI 0.09 to 1.70; participants = 874; studies = 3; I² = 45%; low quality of evidence). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient‐years (4 trials). Effects on other outcomes were very uncertain. Summary effects of RCTs specifically focusing on participants with high cardiovascular risk were similar (4 trials; 1230 participants).

Authors’ conclusions

There is much uncertainty surrounding the benefits and harms of colchicine treatment. Colchicine may have substantial benefits in reducing myocardial infarction in selected high‐risk populations but uncertainty about the size of the effect on survival and other cardiovascular outcomes is high, especially in the general population from which most of the studies in our review were drawn. Colchicine is associated with gastrointestinal side effects based on low‐quality evidence. More evidence from large‐scale randomised trials is needed.

3. Papageorgiou, Nikolaos et al. “Colchicine for prevention and treatment of cardiac diseases: A meta-analysis.” Cardiovascular therapeutics vol. 35,1 (2017): 10-18. doi:10.1111/1755-5922.12226

Type of Article: Meta-analysis

Aims: Colchicine has been suggested to be beneficial in preventing recurrent pericarditis. The goal of this study was to review all randomized controlled trials that assess the use of colchicine for the prevention and treatment of cardiac diseases.

Methods: We performed a meta-analysis of the effects of colchicine on pericarditis, postpericardiotomy syndrome and postprocedural atrial fibrillation recurrence, in-stent restenosis, gastrointestinal adverse effects, and treatment discontinuation rates. We conducted an EMBASE and MEDLINE search for prospective controlled trials.

Results: We identified 17 prospective controlled randomized studies with 2082 patients that received colchicine and 1982 controls with an average follow-up duration of 12 months. Treatment with colchicine is associated with reduced risk of pericarditis recurrence/postpericardiotomy syndrome (OR: 0.37; 95% CI: 0.29-0.47; P<0.001) and lower recurrence of atrial fibrillation rates after cardiac surgery and ablation procedures. However, gastrointestinal side effects were more common in patients treated with colchicine (OR: 2.6; 95% CI: 1.82-3.72; P<0.001) in all subgroups except for those treated for prevention of recurrent pericarditis. The higher rates of side effects resulted in higher incidence of treatment discontinuation in patients treated with colchicine.

Conclusion: Colchicine appears to be efficacious and well tolerated for recurrent pericarditis/postpericardiotomy syndrome and recurrence of postprocedural atrial fibrillation. However, its efficacy may be limited by its gastrointestinal adverse events and treatment discontinuation rates particularly in postoperative patients.

4. Aimo, Alberto et al. “Effect of low-dose colchicine in acute and chronic coronary syndromes: A systematic review and meta-analysis.” European journal of clinical investigation vol. 51,4 (2021): e13464. doi:10.1111/eci.13464

Type of Article: Meta-analysis

Background: Sparse evidence of the prognostic benefit of the anti-inflammatory drug colchicine in chronic and acute coronary syndromes (CCS/ACS) exists.

Methods: We performed a systematic search of studies on CCS or ACS comparing colchicine vs. placebo and reporting data on cardiovascular outcomes (primary end points of each study) and/or changes in hs-CRP.

Results: Ten studies were selected: three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE-PCI; total patient number = 6256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE-PCI; n = 5,654) and five (n = 532) on hs-CRP changes from 1 week to 12 months, in CCS and/or ACS. In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32 to 0.81, P = .005). The favourable effect of colchicine on the risk of cardiovascular events did not change when excluding COLCHICINE-PCI from analysis (HR 0.51, 95% CI 0.25 to 1.03, P = .061). In patients with ACS, the use of colchicine tended to decrease the occurrence of the combined end point compared with placebo (HR = 0.77, 95% CI 0.56 to 1.05, P = .100), and colchicine became significantly protective when removing COLCHICINE-PCI from analysis (HR = 0.72, 95% CI 0.56 to 0.92, P = .009). Furthermore, colchicine tended to reduce the hs-CRP increase (standardized mean difference=-0.31, 95% CI -0.72 to 0.1, P = .133) compared with placebo.

Conclusions: Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs-CRP.

5.  Webb, Carly A, and Arden R Barry. “Colchicine for Secondary Cardiovascular Prevention: A Systematic Review.” Pharmacotherapy vol. 40,6 (2020): 575-583. doi:10.1002/phar.2401

Type of Article: Systematic Review

Abstract

Despite advancements in medical and interventional therapy, patients with cardiovascular disease (CVD) continue to have residual risk for recurrent cardiovascular events. Colchicine has a unique antiinflammatory mechanism that has generated interest in its potential use as a secondary cardiovascular preventive therapy. The objective of this systematic review was to evaluate the evidence for long-term (6 months or more) colchicine therapy in patients with established CVD. A search of Medline and Embase from inception to February 2020 was performed. Included were randomized controlled trials (RCTs) or propensity score-matched observational studies that compared colchicine (at any dose) with placebo or no treatment. Outcomes of interest included any major adverse cardiovascular event, cardiovascular hospitalization, coronary artery restenosis, cardiovascular death, or all-cause death. Five RCTs were included. The dose of colchicine ranged from 0.5 mg/day to 0.6 mg twice/day, and follow-up ranged from ~6-36 months. Two trials (one double blind and one single blind) showed a reduction in composite outcomes of major adverse cardiovascular events. One study failed to demonstrate a benefit with colchicine in restenosis or recurrent ischemia after angioplasty; however, it was conducted before the routine use of modern percutaneous coronary intervention and medical therapies. In contrast, a more recent trial found that colchicine reduced the rate of in-stent restenosis in patients who received a bare metal stent. Finally, one trial in patients with heart failure with reduced ejection fraction did not observe a benefit in death or heart failure hospitalization with colchicine despite a reduction in inflammatory markers. No trial demonstrated a reduction in cardiovascular or all-cause death, and most trials showed an increase in the rate of diarrhea with colchicine. Overall, colchicine has demonstrated promising results for the secondary prevention of CVD; however, further studies are required to confirm these findings before colchicine can be routinely recommended in practice.

6. Xiang, Zujin et al. “Efficacy and safety of colchicine for secondary prevention of coronary heart disease: a systematic review and meta-analysis.” Internal and emergency medicine vol. 16,2 (2021): 487-496. doi:10.1007/s11739-020-02606-7

Type of Article: Meta-Analysis

Abstract

To evaluate the efficacy and safety of colchicine for secondary prevention of coronary heart disease (CHD), relevant randomized controlled trials (RCTs) were identified by searching several databases from the creation date to August 31, 2020 and were reviewed. Eight eligible trials of colchicine therapy involving a total of 11, 463 patients were included (5, 776 subjects received colchicine, while 5, 687 subjects were in the respective control arms), and the outcome was reported as risk ratio (RR) and 95% confidence interval (CI), as the relative measure of association. Overall, the incidences of major adverse cardiovascular events (MACEs) (RR 0.70; 95% CI 0.61-0.80), myocardial infarction (MI) (RR 0.77; 95% CI 0.64-0.94), emergency readmission due to CHD (RR 0.70; 95% CI 0.58-0.86), and ischemic stroke (RR 0.49; 95% CI 0.30-0.79) were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of all-cause mortality (RR 1.03; 95% CI 0.80-1.32). Although the incidence of diarrhea in the colchicine treatment group was higher than that in the placebo arms (RR 2.53; 95% CI 1.17, 5.48), the symptoms disappeared rapidly after drug withdrawal, and no serious adverse reactions occurred. In summary, colchicine is an accessible, safe, and effective drug that could be successfully utilized for the secondary prevention of CHD. The tolerability and benefits should be confirmed in in-depth clinical trials.

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting	Outcome(s) Studied	Key Findings	Limitations And Biases
Samuel (2021)	Meta-analysis	Four RCTs, with a pooled sample size of 11,594 patients, were included (colchicine n=5774; placebo/no colchicine n=5820	The primary composite efficacy endpoint included cardiovascular mortality, myocardial infarction (MI), ischemic stroke, and urgent coronary revascularization.	In sensitivity analyses of ACS trials (COLCOT and COPS; N=5540), the primary composite  endpoint, MI, and urgent coronary revascularizations were statistically significantly reduced in patients  randomized to colchicine compared to placebo   The rates of infections, pneumonias, hospitalizations for  gastrointestinal events, and diagnoses of cancer were also not significantly different   In this contemporary meta-analysis of RCTs comparing colchicine to placebo (or no colchicine) 9 for secondary cardiovascular prevention, we found that: 1) treatment with colchicine was associated  with a 32% reduction in the incidence of major cardiovascular events; 2) significantly fewer MIs,  ischemic strokes, and urgent coronary revascularizations were the primary drivers for the overall  decrease in cardiovascular events; 3) the protective treatment effect of colchicine was relatively  consistent among most subgroups studied, and 4) colchicine had a favorable safety profile	The small number of eligible studies precluded meta-regression analyses to determine the influence of specific variables or effect modifiers  on the association between colchicine and cardiovascular events.
Hemkins (2016)	Systematic Review	39 randomised parallel-group trials with 4992 participants	Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non-scheduled cardiovascular interventions	The primary outcome (a combined endpoint of acute coronary syndrome, out‐of‐hospital cardiac arrest, or noncardio‐embolic ischaemic stroke) was significantly reduced with colchicine treatment   Colchicine had no significant effect on all‐cause mortality across all studies. Moderate quality evidence suggests an 80% risk ratio reduction for myocardial infarction, although most of the evidence was provided by a single study.   Colchicine treatment was associated with an increased RR of 83% for gastrointestinal side effects. These were typically described as mild and transient, including diarrhoea, nausea, abdominal pain, or vomiting.	There were few events in some meta-analyses and some outcome results were dominated by only a single study, which is a clear limitation. For example, effects on myocardial infarction are based on only a small proportion of all randomised participants.
Papageorgiou (2017)	Meta-analysis	Identified 17 prospective controlled randomized studies with 2082 pa- tients that received colchicine and 1982 controls with an average follow-up duration of 12 months.	Effects of colchicine on pericarditis, postpericardiotomy syndrome and postprocedural atrial fibrillation recurrence, in- stent restenosis, gastrointestinal adverse effects, and treatment discontinuation rates.	Only one study assessed the effects of colchicine on cardiovascular events in stable ischemic heart disease and showed decreased rates of cardiovascular events   colchicine was associated with lower recurrence of atrial fibrillation rates after cardiac surgery and ablation procedures, and gastrointestinal side effects were more common in patients treated with colchicine in all subgroups except for those treated for prevention of recurrent pericarditis. The higher rates of side effects resulted in higher incidence of treatment discontinuation in patients treated with colchicine   In the setting of coronary artery disease, the suppression of activated neutrophils contained in atheromas ensures plaque stability and accordingly its diversion to unstable status and onset of acute coronary syndromes.	Any meta- analysis based on pooling of data from different trials with differ- ent inclusion criteria, different designs and populations, variable follow-up duration with differing attrition rates, and not being unified in definition and validation of endpoints in individual trials presents challenges.
Aimo(2020)	Meta-analysis	Ten studies were selected: three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE-PCI; total patient number=6,256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE-PCI; n=5,654), and five (n=532) on hs-CRP changes from 1 week to 12 months, in CCS and/or ACS.	The primary endpoint of LoDoCo2 was a composite of cardiovascular death, MI, ischemic stroke, and ischemia-driven coronary revascularization (5), while LoDoCo and COLCHICINE-PCI considered other composite endpoints	Despite several limitations, including the limited number of studies and heterogeneous endpoints, this meta-analysis shows that LD colchicine near halves the risk of cardiovascular events in CCS Accepted Article This article is protected by copyright. All rights reserved compared with placebo, and causes a non-significant 23% risk reduction in ACS.   Colchicine is a widely available, inexpensive drug, with a satisfactory safety profile and limited drug interactions. Still, further studies are needed before colchicine could enter clinical practice. In the setting of CCS, the influence of circulating levels of inflammatory biomarkers and baseline cardiovascular risk on colchicine efficacy should be examined.   Five small-scale studies (3,8-11) (n=532 patients overall) evaluated the effects of colchicine therapy on changes in hs-CRP from baseline to specific timepoints (from 1 week to 12 months), in the setting of CCS, ACS, or patients undergoing PCI. Colchicine tended to reduce the hs-CRP increase.	limited number of studies and heterogeneous endpoints
Webb (2020)	Systematic Review	Five studies met the inclusion criteria, all of which were RCTs comprising a total of 5949 patients	Outcomes of interest included any major adverse cardiovascular event, car- diovascular hospitalization, coronary artery restenosis, cardiovascular death, or all-cause death	This systematic review evaluated the current published data for the long-term use (6 months or longer) of colchicine as preventive therapy in patients with CVD. Overall, the evidence for col- chicine in secondary cardiovascular protection is promising; two large randomized trials showed a reduction in a composite cardiovascular end point with colchicine   An additional trial showed a reduc- tion in in-stent restenosis in patients who received PCI with bare metal stent implantation. However, most trials also showed an increase in adverse events, particularly diarrhea, and no trial identified a reduction in cardiovascular or all- cause death.	Only one of the trials was double blind and placebo controlled, and the composite outcome in that trial was driven by a reduction in stroke and hospitalization for angina.
Xiang (2021)	Meta-analysis	Eight eligible trials of colchicine therapy involving a total of 11, 463 patients were included	The incidence of major adverse cardiovascular events (MACEs) includes cardiac death, cardiac arrest resuscita- tion, ventricular arrhythmia, stent thrombosis, acute myo- cardial infarction (AMI), emergency coronary revasculariza- tion, acute heart failure, and ischemic stroke.	Our study indicates for the first time that colchicine is beneficial to the entire coronary heart disease population, including both stable CHD patients and patients with ACS and both percu- taneous coronary intervention (PCI) postoperative patients and patients with stable angina.   After all, low-dose colchicine plays a cardiovascular protective role by continuously combating the residual inflammatory risk rather than rapidly reducing the higher inflammatory level in the short term	There are still some limitations in our meta-analysis. First, the subjects were mostly high-risk patients with CHD, including AMI. Therefore, the impact of colchicine on all-cause mortality needs to be evaluated in general CHD patients. Second, the follow-up of all the eligible studies was less than 3 years, so relevant clinical trials with longer follow-up are necessary to more scientifically evaluate the long-term safety and efficacy of colchicine.

Conclusions:

Samuel (2021) concluded that the risk of overall cardiac events is reduced with using colchicine without reducing overall mortality.  

Hemkens (2016) conclude that colchicine was also effective in reducing future MI but the effects on overall mortality remain inconclusive.

Papageorgiou (2020) concluded that colchicine was effective in preventing recurrent pericarditis and pericardiotomy syndrome, but may have limited use due to its gastrointestinal side effects.

Aimo (2021) concluded that the risk of cardiovascular events was halved in those with chronic coronary syndrome, and reduced markers of inflammation.

Webb (2020) concluded that longer term (~ 6 month) colchicine therapy was effective in reducing in-stent restenosis as well as stroke and hospitalization for angina.

Xiang (2021) concluded that colchicine effectively reduced risk of stroke, MI, and emergency admission for CVD without affecting overall mortality.

Overall: All 6 of these studies demonstrate that colchicine is a cheap and effective means to reduce risk of major adverse cardiac events, albeit with no definitive effects on overall mortality.

Clinical Bottom Line

Articles Ranked:

Xiang (2021) was rated first due to the measuring of several pertinent outcomes with over 5,500 patients. It was also published very recently and includes several other analyses in their evaluation.

Samuel (2021) was rated second as it was also published recently and evaluated randomized placebo- controlled trials. They also looked at stroke, MI, and urgent coronary revascularization as endpoints for the study.

Webb (2020) was rated third because they evaluated longer term therapy of colchicine as preventive therapy, which provides a better overview of safety and efficacy.

Aimo (2021) was rated fourth because they evaluated the efficacy of colchicine in both chronic coronary syndrome and acute coronary syndrome.

Hemkens (2016) was rated fifth because it was the oldest study and had a smaller sample size than other articles listed.  

Papageorgiou (2020) was rated sixth because they looked primarily at pericarditis and pericardiotomy syndrome, and not MI or stroke as the other studies did. I included it regardless because they are still inflammatory heart conditions.  

Magnitude of Effects

Across nearly all the studies, it was determined that colchicine was a cheap and effective intervention for prevention of further cardiovascular accidents, but might not affect overall mortality in these patients.

Xiang (2021) – Overall, the incidences of major adverse cardiovascular events (MACEs) (RR 0.70; 95% CI 0.61-0.80), myocardial infarction (MI) (RR 0.77; 95% CI 0.64-0.94), emergency readmission due to CHD (RR 0.70; 95% CI 0.58-0.86), and ischemic stroke (RR 0.49; 95% CI 0.30-0.79) were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of all-cause mortality (RR 1.03; 95% CI 0.80-1.32).

Samuel (2021) – Colchicine was associated with a statistically significant reduction in the incidence of the primary composite endpoint (pooled HR, 0.68; 95% CI, 0.54-0.81; I2 = 37.7%)

Webb (2020) – Colchicine reduced the primary composite outcome of cardiovascular death, resuscitated cardiac arrest, MI, non-cardioembolic ischemic stroke, or urgent hospitalization for angina leading to revascularization (5.5% vs 7.1%, HR 0.77, 95% CI 0.61–0.96), as well as the individual outcomes of urgent hospitalization for angina (1.1% vs 2.1%, HR 0.50, 95% CI 0.31–0.81) and non- cardioembolic ischemic stroke (0.2% vs 0.8%, HR 0.26, 95% CI 0.10–0.70).

Aimo (2021) – In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32 to 0.81, P = .005).

Hemkens (2016) – There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence).

Papageorgiou (2020) – Treatment with colchicine is associated with reduced risk of pericarditis recurrence/postpericardiotomy syndrome (OR: 0.37; 95% CI: 0.29-0.47; P<0.001) and lower recurrence of atrial fibrillation rates after cardiac surgery and ablation procedures

 Clinical Significance:

The clinical bottom line is that colchicine is associated with an effective reduction in recurrent cardiac events, even with a dose as low as 0.5mg. Compared to placebo, colchicine was associated with preventing myocardial infarctions, atrial fibrillation, and episodes of acute coronary syndrome, assessed at time periods up to 1 year after starting therapy. Colchicine has several different pathways to blunt vascular inflammation and helps to promote the stability of atherosclerotic plaques, decreasing the chance of progression to a severely adverse event. Colchicine is also inexpensive and has few drug interactions. Despite these anti-inflammatory effects and reductions in major cardiovascular adverse events, colchicine may not reduce overall mortality in these patients.

Additional Considerations:

However, there can be some adverse gastrointestinal issues reported, such as nausea, diarrhea, vomiting and abdominal pain, that some patients may be unable to tolerate, and more trials need to conducted to evaluate long-term safety of colchicine therapy. Trials may also be limited by confounding factors. Patients may be taking concurrent medications for their cardiovascular disease, such as aspirin, or may have different comorbidities. Patients may also have more or less severe progression of coronary artery disease, which can affect outcomes. More trials should also be conducted to evaluate the long term efficacy and safety of colchicine, as well as determine the likelihood of developing adverse reactions.