Background: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.

Methods: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.

Results: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03).

Conclusions: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

https://www-nejm-org.york.ezproxy.cuny.edu/doi/pdf/10.1056%2FNEJMoa1912388

Methods and results: Patients presenting with ST-segment-elevation myocardial infarction ≤12 hours from pain onset (treated with primary percutaneous coronary intervention) were randomly assigned to colchicine or placebo for 5 days. The primary outcome parameter was the area under the curve of creatine kinase-myocardial brain fraction concentration. A subset of patients underwent cardiac MRI with late gadolinium enhancement 6 to 9 days after the index ST-segment-elevation myocardial infarction. One hundred fifty-one patients were included (60 in the MRI substudy). The area under the creatine kinase-myocardial brain fraction curve was 3144 (interquartile range [IQR], 1754-6940) ng·h(-1)·mL(-1) in the colchicine group in comparison with 6184 (IQR, 4456-6980) ng·h(-1)·mL(-1) in controls (P<0.001). Indexed MRI-late gadolinium enhancement-defined infarct size was 18.3 (IQR, 7.6-29.9) mL/1.73 m(2) in the colchicine group versus 23.2 (18.5-33.4) mL/1.73 m(2) in controls (P=0.019). The relative infarct size (as a proportion to left ventricular myocardial volume) was 13.0 (IQR, 8.0-25.3) % and 19.8 (IQR, 13.7-29.8) %, respectively (P=0.034).

Conclusions: These results suggest a potential benefit of colchicine in ST-segment-elevation myocardial infarction, but further clinical trials are necessary to draw secure conclusions, especially considering the fact that the present study was not powered to assess clinical end points.

Following an acute myocardial infarction (MI), patients with persistently elevated biomarkers of inflammation, in particular C-reactive protein (CRP), are at significantly increased risk of further cardiovascular events. Colchicine is a unique anti-inflammatory medication that has shown promise in reducing such events in patients with stable coronary heart disease. The current study tested the ability of low dose colchicine to reduce CRP levels at 30 days after an acute MI, a key marker of future outcome, and its safety and tolerability in this setting.

Methods: We conducted a randomized, double-blind, trial of low-dose colchicine (0.5 mg daily) or matching placebo in 237 patients admitted with an acute MI. The primary end-point was the proportion of patients with a residual high sensitivity CRP level ≥2 mg/L after 30 days of treatment, a threshold associated with a worse prognosis.

Results: At 30-day follow-up, 44% of patients treated with colchicine had a CRP level ≥2 mg/L compared to 50% of those randomized to placebo (P = .35) and the median CRP in patients randomized to colchicine was 1.6 mg/L (interquartile range [IQR] 0.7-3.5) compared to 2.0 mg/L (IQR 0.9-4.0) in patients randomized to placebo (P = .11). The median absolute reduction in CRP levels was -4.3 mg/L (IQR -1.1 to -14.1) among colchicine treated patients and -3.3 mg/L (IQR -0.9 to -14.4, P = .44) in placebo treated patients. The relative reduction was a fall of 78% compared to a fall of 64% (P = .09). Low dose colchicine was well tolerated and did not reduce compliance with other secondary preventative medications at 30-days.

Conclusion: Treatment with low dose colchicine was safe and well tolerated, but was not associated with a significantly increased likelihood of achieving a CRP level <2 mg/L or lower absolute levels of CRP 30 days after an acute MI.

https://www.sciencedirect.com/science/article/abs/pii/S0002870319301486

Background: Inflammation is involved during acute myocardial infarction, and could be an interesting target to prevent ischaemia-reperfusion injuries. Colchicine, known for its pleiotropic anti-inflammatory effects, could decrease systemic inflammation in this context.

Aims: To evaluate the impact of colchicine on inflammation in patients admitted for ST-segment elevation myocardial infarction (STEMI).

Methods: All patients admitted for STEMI with one of the main coronary arteries occluded, and successfully treated with percutaneous coronary intervention, were included consecutively. Patients were randomized to receive either 1mg colchicine once daily for 1 month plus optimal medical treatment or optimal medical treatment only. C-reactive protein (CRP) was assessed at admission and daily until hospital discharge. The primary endpoint was CRP peak value during the index hospitalization.

Results: Forty-four patients were included: 23 were treated with colchicine; 21 received conventional treatment only. At baseline, both groups were well balanced regarding age, sex, risk factors, thrombolysis in myocardial infarction flow and reperfusion delay. The culprit artery was more often the left anterior descending artery in the colchicine group (P=0.07), reflecting a more severe group. There was no significant difference in mean CRP peak value between the colchicine and control groups (29.03mg/L vs 21.86mg/L, respectively; P=0.36), even after adjustment for type of culprit artery (26.99 vs 24.99mg/L, respectively; P=0.79).

Conclusion: In our study, the effect of colchicine on inflammation in the context of STEMI could not be demonstrated. Further larger studies may clarify the impact of colchicine in acute myocardial infarction.

Keywords: Acute coronary syndrome; Cardiovascular disease; Colchicine; Heart failure; Infarctus du myocarde; Insuffisance cardiaque; Myocardial infarction; Pathologies cardiovasculaires; Syndrome coronarien aigu.

https://reader.elsevier.com/reader/sd/pii/S1875213616302121?token=DCF110A8D2D5465A213034BE74A0A2841482AFF244259A76239DCEF5684A4B9F5F7B246A6F2D8EADF0EDF5D039FC4DA1

(# of subjects/ studies, cohort definition etc. )

– Mandatory inclusion criteria: adults who had an MI within the past 30 days, underwent any percutaneous revascularization procedures needed, and were treated according to national guidelines (such as statin use).

-Exclusion criteria included severe heart failure LVEF <35%, CVA within 3 months, etc.

– Patients were randomly assigned to either the colchicine or placebo group. 2226 patients received 0.5 mg PO once daily of colchicine and 2232 received placebo.

– Diarrhea occurred in 9.7% of the colchicine group and 8.9% of the placebo. Pneumonia occurred in 0.9% of the colchicine group and 0.4% of the placebo group. Infection occurred in 2.2% of the colchicine group and 1.6% of the placebo.

(# of subjects/ studies, cohort definition etc. )

-Prospective, double-blinded RCT in hospitals in Athens, Greece

-AUC of CK-MB was 3144 in ng·h·mL–1 in the colchicine group compared to 6184 ng·h·mL–1 in the placebo group (P<0.001)

-20/77 (26%) patients in the colchicine group stopped the drug within the five days, because of diarrhea, nausea, or vomiting for all but one patient (elevated ALT).

The sample was mostly male (104/151), thus affecting generalization of results to females. The males were however split evenly between the two groups.

(# of subjects/ studies, cohort definition etc. )

– Results were from 111 participants in the colchicine group (0.5 mg PO daily) and 111 in the placebo group, followed for 30 days

-All patients were from one single hospital in Australia

– The relative reduction in CRP was 78% for the colchicine group versus 64% for the placebo group.

Colchicine was found to be very safe and had good compliance and tolerance. Furthermore, the addition of colchicine was not found to reduce compliance with the rest of the patient’s treatment regimen.

-Furthermore, it only followed patients for 30 days, which may not have been enough time to see a more complete magnitude of effects.

(# of subjects/ studies, cohort definition etc. )

-44 patients total: 23 patients were given 1 mg colchicine PO daily for 1 month along with optimal medical treatment and 21 patients received optimal medical treatment only.

– Exclusion criteria included “cardiogenic shock, severe chronic kidney failure (clearance < 30 mL/kg/min), colchicine intolerance or contraindication” etc. (Akodad et. al).

-Secondary endpoints included major adverse effects, patient tolerance of colchicine, etc.

– After 30 days, neither group had a higher rate of severe adverse effects than the other.