Background
Methods
Data sources
Study selection
Data extraction and quality assessment
Data analysis
Results
Description of included studies and quality assessment
Stable CAD | ACS (91 %) or Acute Stroke (9 %) | Post Successful Elective Balloon PTCA | Post BMS PTCA in DM (31 % ACS) | Symptomatic stable CHF with LVEF ≤ 40 % | |
---|---|---|---|---|---|
Colchicine Dose | 0.5 mg/d | 1 mg/d | 0.5 mg bid | 0.5 mg bid | 0.5 mg bid |
Trial | Nidorf 2013 [14] | Raju 2012 [15] | O’Keefe 1992 [16] | Deftereos 2013 [7] | Deftereos 2014 [17] |
N = 532 | N = 80 | N = 197 | N = 222 | N = 267 | |
Trial Characteristics
| |||||
No. Centres | 1 | 1 | 1 | 1 | 1 |
Enrolment period | Aug 2008 – May 2010 | Apr 2008 – Aug 2009 | n/r | n/r | n/r |
Treatment/Follow Up | 2 (all)/3 (median) yrs | 32 days (median) | 5.5 months (mean) | 6 months (?all) | 6 months (all) |
Funding | None | Public | n/r | n/r | n/r |
Patients
| N = 532 | N = 80 | N = 197 | N = 196 | N = 279 |
Mean Age (years) | 66 | 57 | 60 | 64 | 67 |
% Male | 89 % | 88 % | 86 % | 65 % | 67 % |
BMI | 27 | 26 | |||
Diabetes | 31 % | 16 % | 12 % | 100 % | 17 % |
HTN | 42 % | 49 % | 36 % | ||
Smoker | 5 % | 44 % | 38 % | ||
Dyslipidemia | 48 % | Total Chol 211 mg/dL | 33 % | ||
Prev MI/UA | 23 % | 18 % | |||
Prev stroke/TIA | 4 % | ||||
PVD | 5 % | ||||
CRD | n/r | Excl CrCl <50 mL/min | Excl Cr ≥2.5 mg/dL/ 221 μM | 33 % (Excl CrCl <20 mL/min) | Excl eGFR <30 mL/min |
Mean LVEF | 56 % | 28 % | |||
Previous CABG | 19 % (Prev PCI 58 %) | 26 % | |||
Medications
| |||||
ASA and/or clopidogrel | 93 % (DAPT 12 %) | 100 % (DAPT 85 %) | |||
Statin | 95 % | 98 % | 63 % | ||
Beta-Blocker | 67 % | 79 % | |||
Calcium Channel Blocker | 14 % | ||||
ACE Inhibitor | 58 % | 85 % (incl ARB) | |||
Diuretic | 69 % |
Acute Pericarditis | Acute Pericarditis | First Re-current Pericarditis | First Re-current Pericarditis | Multiply Recurrent Pericarditis | Post Pericardiotomy Syndrome | Post Pericardiotomy Syndrome | Post Pericardiotomy Syndrome | Post Pericardiotomy Syndrome | Post RF Ablation for Recurrent AFib | |
---|---|---|---|---|---|---|---|---|---|---|
Colchicine Dose | 0.25-0.5 mg bid (lower dose <70 kg or intolerance) | 0.5 mg bid (daily ≤70 kg or intolerance) | 0.25-0.5 mg bid (lower dose <70 kg or intolerance) | 0.25-0.5 mg bid (lower dose <70 kg or intolerance) | 0.5 mg bid (daily ≤70 kg or intolerance) | 1.5 mg/d starting POD #3 | 0.5 mg bid (daily <70 kg) starting POD #3 with loading dose | 0.5 mg bid (daily <70 kg) starting 48-72 h pre-op | 0.5 mg bid | 0.5 mg bid |
Trial | COPE (Imazio) 2005 [18] | ICAP (Imazio) 2013 [19] | CORE (Imazio) 2005 [20] | CORP (Imazio) 2011 [21] | CORP-2 (Imazio) 2014 [22 | Finkelstein 2002 [23] | COPPS (Imazio) 2010 [24] | COPPS-2 (Imazio) 2014 [25] | Sarzaeem 2014 [26] | Deftereos 2012 [27] |
N = 120 | N = 240 | N = 84 | N = 120 | N = 240 | N = 163 | N = 360 | N = 360 | N = 216 | N = 230 | |
Trial Characteristics
| ||||||||||
No. Centres | 2 | 5 | 1 | 4 | 4 | 2 | 6 | 11 | 1 | 3 |
Enrolment period | Jan 2002 – Aug 2004 | Aug 2005 – Dec 2010 | Jan 2001 – Aug 2004 | Aug 2005 – Apr 2009 | Nov 2005 – Jan 2012 | Oct 1997 – Sept 1998 | n/r | Mar 2012 – Mar 2014 | Jan 2013 –Jul 2013 | n/r |
Treatment/ Follow Up | 3 months/24 months (mean) | 3 months/18 months (all)/ 22 months (mean) | 6 months/20 months (mean) | 6 months/ 18 months (all)/ 23 months (mean) | 6 months/18 months (all)/ 20 months (mean) | 1 month/3 months | 1 month/19 months (mean) | 1 month/3 months | 7 days/Hosp discharge (mean 7 days) | 3 months/15 (median) months |
Funding | Public | Public | Public | Public | Public | n/r | Public | Public | n/r | n/r |
Patients
| N = 120 | N = 240 | N = 84 | N = 120 | N = 240 | N = 111 | N = 360 | N = 360 | N = 216 | N = 206 |
Mean Age (years) | 57 | 52 | 54 | 48 | 49 | 64 | 66 | 68 | 60 | 62 |
% Male | 45 % | 60 % | 35 % | 53 % | 50 % | 73 % | 67 % | 69 % | 72 % | 70 % |
BMI | 26 | 26 | ||||||||
Diabetes | 3 % | 27 % | 23 % | 22 % | 37 % | 25 % | ||||
HTN | 23 % | 46 % | 68 % | 68 % | 53 % | 41 % | ||||
Smoker | 49 % | 48 % | 13 % | 29 % | 30 % | 35 % | ||||
Dyslipidemia | 42 % | |||||||||
Prev MI/UA | 11 % | 7 % | 40 % | 21 % | 34 % (CAD) | |||||
Prev stroke/TIA | 2 % | |||||||||
PVD | ||||||||||
CRD | (Excl Cr >2.5 mg/dL/ 221 μM) | (Excl Cr >2.5 mg/dL/ 221 μM) | (Excl Cr >2.5 mg/dL/ 221 μM) | 5 % (CrCl <60 mL/min; Excl Cr >2.5 mg/dL/ 221 μM) | (Excl Cr >2.5 mg/dL/ 221 μM) | 15 % (CrCl <60 mL/min; Excl Cr >2.5 mg/dL/ 221 μM) | 7 % (Excl Cr >2.5 mg/dL/ 221 μM) | Excl | Excl eGFR <30 mL/min | |
Mean LVEF | 58 % | 54 % | 55 % | 47 % | 55 % | |||||
Previous CABG | 6 % | 4 % | 6 % | 6 % | Excl | |||||
Medications
| ||||||||||
ASA and/or clopidogrel | 76 % (ASA) | 76 % (ASA) | ||||||||
Statin | 37 % | |||||||||
Beta-Blocker | 36 % | |||||||||
Calcium Channel Blocker | 41 % | |||||||||
ACE Inhibitor | 54 % (incl ARB) | |||||||||
Diuretic |
Trial | Follow up duration | Blinded | Concealed allocation | Intention to treat analysis | Not stopped early for benefit | <5 % Randomized Patients with Missing Outcome Data |
---|---|---|---|---|---|---|
Nidorf 2013 [14] | 3 years (median) [minimum 2 years] | Outcome assessors only | Yes | Yes | Yes | Yes (0 %, 0/532) |
Raju 2012 [15] | 32 days (median) | Yes | Yes | Yes | Yes | No (7.3 %, 6/82) |
O’Keefe 1992 [16] | 5.5 months (mean) | Yes | n/r | n/r | Yes | Unclear (unsuccessful PTCA patients excluded but randomized before PTCA) |
Deftereos 2013 [7] | 6 months (all) | Yes | n/r | Yes | Yes | Yes (0 %, 0/222 [clinical outcomes]) |
Deftereos 2014 [17] | 6 months (all) | Yes | n/r | Yes | Yes | Yes (1.1 %, 3/279) |
Finkelstein 2002 [23] | 3 months (all) | Yes | n/r | Yes | Yes | No (32 %, 52/163) |
COPE 2005 (Imazio) [18] | 20 months (mean) | No | n/r | Yes | n/r | Yes (0 %) |
ICAP 2013 (Imazio) [19] | 18 months (all)/ 22 months (mean) | Yes | Yes | Yes | Yes | Yes (0 %) |
CORE 2005 (Imazio) [20] | 18 months (all)/ 20 months (mean) | No | n/r | Yes | n/r | Yes (0 %) |
CORP 2011 (Imazio) [28] | 18 months (all)/ 23 months (mean) | Yes | Yes | Yes | Yes | Yes (0 %) |
CORP-2 2014 (Imazio) [22] | 18 months (all)/ 20 months (mean) | Yes | Yes | Yes | Yes | Yes (0 %) |
19 months (mean) | Yes | Yes | Yes | Yes | Yes (0 %) | |
COPPS-2 2014 (Imazio) [25] | 3 months (median) | Yes | Yes | Yes | Yes | Yes (0 %) |
Sarzaeem 2014 [26] | 7 days (mean) (hospital discharge) | Yes | n/r | n/r | Yes | Unclear (excluded patients unable to tolerate enteral medications within 48 h post cardiac surgery) |
3 months (?all)/ 15 months (median) | Yes | n/r | Yes | Yes | No (10 %, 24/230 [AFib recurrence]; 6.1 %, 14/230 [adverse events]) |
Quantitative data synthesis
Discussion
Stable Cardiovascular Disease |
ACTRN12614000093684 - The LoDoCo2 Trial: A randomised controlled trial on the effect of low dose Colchicine for secondary prevention of cardiovascular disease in patients with established, stable coronary artery disease. This study is not yet recruiting. Sponsor: Heart Research Institute of Western Australia/Aspen Pharmacare Australia. Target enrolment: 3000 patients. |
NCT02153983 - Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome. This study is currently recruiting participants. Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Target enrolment: 100 patients. |
NCT02162303 - Colchicine in Vascular Inflammation Assessed With PET Imaging (COLPET). This study is currently recruiting participants. Sponsor: Montreal Heart Institute. Target enrolment: 106 patients. |
Acute Coronary Syndrome |
NCT01906749 - Colchicine for Acute Coronary Syndromes (COACS). This study is currently recruiting participants. Sponsor: Maria Vittoria Hospital. Target enrolment: 500 patients. |
NCT01936285 - Colchicine in ST-elevation Myocardial Infarction. This study is currently recruiting participants. Sponsor: G. Gennimatas General Hospital. Target enrolment: 75 patients. |
NCT02095522 - COlchicine Improve EnDothElial Function in Non ST Elevation Myocardial Infarction Patients (CODEN). This study is not yet open for participant recruitment. Sponsor: Tel-Aviv Sourasky Medical Center. Target enrolment: 100 patients. |
Percutaneous Intervention |
NCT01709981 - Anti-inflammatory Effects of Colchicine in PCI. This study is currently recruiting participants. Sponsor: New York University School of Medicine. Target enrolment: 400 patients. |
Post-Operative |
ISRCTN72835417. COlchicine for the preVention of postopErative atrial fibRillation in patients undergoing Coronary Artery By-pass Grafting (COVER CABG). Completed. Sponsor: Catholic University of the Sacred Heart-Rome (Italy). Target enrolment: 320 patients. |
ACTRN12613001345774 - Colchicine for the Primary Prevention of Atrial Fibrillation after Cardiac Surgery: A Double Blind Placebo Randomised Controlled Trial. Recruiting. Sponsor: Barwon Health - The Geelong Hospital. Target enrolment: 520 patients. |
NCT01266694 - Cochicine Treatment for Post- Operative Pericardial Effusion (POPE2). This study has been completed. Sponsor: French Cardiology Society. Target enrolment: 199 patients. |
NCT01985425 - Colchicine For Prevention of Perioperative Atrial Fibrillation in Patients Undergoing Thoracic Surgery Pilot Study (COP-AF Pilot) This study is currently recruiting participants. Sponsor: McMaster University. Target enrolment: 100 patients. |
NCT02122484 - Colchicine in Coronary Artery Bypass Graft (CABG). This study is ongoing, but not recruiting participants. Sponsor: G.Gennimatas General Hospital. Target enrolment: 75 patients. |
NCT02177266 - Colchicine to Prevent Post-Pericardiotomy Syndrome and Atrial Fibrillation. This study is not yet open for participant recruitment. Sponsor: Mayo Clinic. Target enrolment: 242 patients. |
Chronic Atrial Fibrillation |
NCT01755949 - Impact and Time Course of Colchicine Therapy on C-reactive Protein Elevation in Chronic Atrial Fibrillation and Post AF Ablation. This study is currently recruiting participants. Sponsor: Mayo Clinic. Target enrolment: 60 patients. |
Excluded Trial | Patient Inclusion | Number of Patients/Centres | Intervention | Control | Follow Up Duration | Outcomes | Reason for Exclusion |
---|---|---|---|---|---|---|---|
Prevention of Post-Op Afib | |||||||
Saenen et al. Eur Heart J 2013 [Abstract] [38] | Post CABG | 40/single | Peri-operative Colchicine | Placebo | 1 hour post CABG | Right Atrial Appendage Biopsy Pathology | Only pathology data provided |
Nidorf & Thompson Am J Card 2007 [39] | Stable CAD | 64/single | Colchicine | Control | 4 weeks | C-reactive protein | Not randomized |
Freed et al. Am J Card 1995 [40] | Post PTCA | 5/single | Cochicine + Enalapril + Lovastatin | n/a | 5 months | Death, MI, revasc. | Not randomized |
Rab et al. JACC 1991 [41] | Post BMS PTCA | 29/single | Colchicine + gluco-corticoids | Gluco-corticoids | 4 months | Coronary artery aneurysm | Not randomized |
Judkins et al. Heart Lung Circ 2011 [Abstract] [42] | Stable CAD | 50/single | Colchicine | Control | 6 months | C-reactive protein; flow mediated dilation | Cross over RCT |
Luo & Yang. Hong Kong Med J 2001 [Abstract] [43] | Acute stroke | n/a | Colchicine, Cyclo-phosphamide plus Magnesium | Control | n/a | n/a | Combined intervention |
Xu et al. West China Med J 1999 [Chinese] [44] | Acute stroke | 64/single | Colchicine and Cyclo-phosphamide | Control | 3 months | Neurological outcomes | Combined intervention |
Liu et al. Chin J Geriat Cardiovasc Cerebrovasc Dis 2002 [Chinese] [45] | Acute stroke | 325/multi | Colchicine and Cyclo-phosphamide | Control | 3 months | Neurological outcomes, serum enolase, adverse events | Combined intervention |