Table 1.
Clinical trials of colchicine in treating cardiovascular diseases (completed).
| Study | Setting | Patient | Colchicine regimen | Outcome | Findings | Conclusion | Ref. |
|---|---|---|---|---|---|---|---|
| Atherosclerosis | |||||||
| LoDoCo |
Receiving Colchicine (n = 282) Control (n = 250) |
Patients with stable CAD (n = 532), followed up for median of 3 years. | 0.5 mg/day | Acute coronary syndrome (ACS), fatal, out-of-hospital cardiac arrest, noncardioembolic ischemic stroke. |
Lower endpoint in colchicine treatment (5.3%: 16%; P < 0.001) Lower risk of ACS in colchicine group (4.6%: 13.4%; P < 0.001) |
Standard therapy compared with colchicine (0.5 mg/day) reduces the risk of cardiovascular events, including noncardioembolic ischemic stroke, out-of-hospital cardiac arrest, and ACS. | [12] |
| LoDoCo2 |
Receiving Colchicine (n = 2,762) Placebo (n = 2,760) |
Patients of coronary disease (n = 5,522), followed up for 28.6 months. | 0.5 mg/day | Cardiovascular death, spontaneous myocardial infarction, ischemic stroke, coronary revascularization driven by ischemia. |
Lower risk of endpoint shown in colchicine group (6.8%: 9.6%; HR: 0.69; 95% CI: 0.57–0.83, P < 0.001) Lower risk of ischemia-driven coronary or revascularization spontaneous myocardial infarction or, cardiovascular death or spontaneous MI in colchicine group. |
Colchicine (0.5 mg/day) decreases 31% risk of cardiovascular events, including spontaneous myocardial infarction, death, ischemic stroke. | [170] |
| COLCOT |
Receiving Colchicine (n = 2,322) Placebo (n = 2,339) |
Patients within 30 day post-MI (n = 4,661), followed up for 22.7 months. | 0.5 mg/day, | Cardiovascular death, MI, urgent hospitalization for angina requiring coronary resuscitated cardiac arrest, and stroke. | After MI, uptake of colchicine in the first 3 days could reduce the risk of endpoint (4.3%: 8.3%; P < 0.007). | It is more beneficial for patients to get early colchicine treatment in hospital. | |
| Raju et al. |
Receiving Colchicine (n = 40) Placebo (n = 40) |
Patients with acute ischemic stroke (n = 7) or ACS (n = 73), followed up for 30 days. | 1 mg/day | Death, level of hsCRP, and stroke or MI at 30 days as clinical outcomes. | No difference in level of hsCRP in colchicine and placebo group (1.0 mg/L: 4.5 mg/L; P = 0.22). | 1.0 mg/day of colchicine does not reduce blood level of hsCRP. Colchicine has no effect on platelet function. | [171] |
| Martinez et al. |
Receiving Colchicine (n = 21 + 13) Control (n = 19 + 20) |
Patients with cardiac catheterization (Stable CAD n = 33; ACS n = 40; control n = 10) | 1 mg followed by 0.5 mg 1 h later | Level of IL-1β, IL-6, and IL-18 in 6–24 h prior to cardiac catheterization. | Colchicine decreases the level of cytokines in ACS patients by 40%–88% (P = 0.028, 0.032, and 0.032 for IL-1β, IL-6, and IL-18, respectively) | Short-term colchicine administration significantly decreases the level of inflammatory cytokines. | [172] |
| MBBS et al. |
Receiving Colchicine + OMT (n = 40) OMT (n = 40) |
Patients with recent ACS (<1 month, n = 80), followed up for 1 year. | 0.5 mg/day | Low attenuation plaque volume (LAPV) |
Colchicine significantly reduces the level of hsCRP (1.1 mg/L: 0.38 mg/L; P < 0.001) and LAPV (15.9 mm3: 6.6 mm3; P = 0.008). No difference in low-density lipoprotein (0.44 mmol/L: 0.49 mmol/L; P = 0.21). |
Low-dose colchicine reduces coronary plaque, independent of low-density lipoprotein. | [173] |
| COPS |
Receiving Colchicine (n = 396) Placebo (n = 399) |
Patients with ACS and CAD on coronary angiography, followed up for 12 months. | First months: 0.5 mg twice a day, 0.5 mg/day for 11 months. | ACS, noncardioembolic ischemic stroke, ischemia-driven urgent revascularization, and all-cause mortality. |
Higher total death rate in colchicine (8: 1; P = 0.017), and non-cardiovascular death (5: 0; P = 0.024). No difference for endpoint between two groups (61.0%: 9.5%; P = 0.09). |
There is no significant effect on cardiovascular outcomes for adding colchicine to standard medical therapy at 12 months in patients with ACS, but with higher rate of mortality. | [174] |
| Pericarditis | |||||||
|
CORE Imazio et al. |
Receiving Aspirin + Colchicine n = 42) Aspirin (n = 42) |
Patients first suffering from recurrent pericarditis (n = 84), followed up for 6 months | First day: 1.0–2.0 mg; 0.5–1.0 mg/d for 6 months |
Recurrence rate; Symptom persistence 72 h after treatment onset. |
Colchicine decreases the recurrence rate (24%: 50.6%; P = 0.02). No severe adverse events are observed. |
Colchicine decreases the risk of recurrence of pericarditis in patients first suffering from recurrent pericarditis. | [27] |
|
COPE Imazio et al. |
Receiving Aspirin + Colchicine n = 60) Aspirin (n = 60) |
Patients first suffering from recurrent pericarditis (n = 120), followed up for 3 months | First day: 1.0–2.0 mg and 0.5–1 mg/day for 3 months | Recurrence rate; |
Colchicine decreases the risk of symptom persistence at 72 h (11.7%: 36.7%; P = 0.003) and recurrence (10.7%: 32.3%; P = 0.004). No serious adverse effect is observed. |
Colchicine is beneficial over conventional treatment. It decreases the rate of recurrence in patient first suffering from recurrent pericarditis. | [175] |
|
CORP Imazio et al. |
Receiving Colchicine n = 60) Placebo (n = 60) |
Patients first suffering from recurrent pericarditis (n = 120), followed up for 6 months | 1.0–2.0 mg on the first day and 0.5–1 mg/day for 6 months | Recurrence rate at 18 months. |
Lower risk of recurrence is observed in colchicine group (24%: 55%; P < 0.001). Colchicine decreases the persistent symptoms at 72 h (23%: 53%; P = 0.001) |
Colchicine is efficacious and relatively safe for preventing recurrent pericarditis. | [28] |
| Imazio et al. |
Receiving Colchicine n = 120) Aspirin (n = 120) |
Patients first suffering from recurrent pericarditis (n = 240), followed up for 3 months | Weight >70 kg: 0.5 mg twice a day; weight ≤70 kg: 0.5 mg/day in 3 months | Incessant or recurrent pericarditis | Colchicine decreases the occurrence of incessant or recurrent pericarditis (16.7%: 37.5%; P < 0.001) and symptom persistence at 72 h (19.2%: 40.4%; P = 0.001). | Colchicine reduces incessant or recurrent pericarditis risk in patients with acute pericarditis. | [176] |
| Guindo et al. | Receiving Colchicine (n = 9) | Patients with recurrent pericarditis, and at least experienced three recurrences., followed up for mean 24.3 months. | 1 mg/day | / |
No recurrence has been observed after colchicine treatment in mean 24.3 months. Seven of nine patients have double period without symptom compared with before colchicine treatment. They supposed that colchicine prevents recurrences effectively when the flare-up is controlled by a corticosteroid. |
[26] | |
| Papageorgiou et al. |
Receiving Colchicine (n = 2,082) Control (n = 1,982) |
Meta-analysis 17 studies involving 4,064 patients, followed up for mean 12 months |
/ | Pericarditis recurrence and postpericardiotomy syndrome; recurrence of atrial fibrillation; in-stent restenosis; | Colchicine decreases the risk of pericarditis recurrence (18.4%: 42%; P = 0.001) | Colchicine shows a good effect on recurrent pericarditis. | [29] |
| Restenosis | |||||||
| James et al. |
Receiving Colchicine (n = 111) Placebo (n = 58) |
Patients with coronary angioplasty, followed up for 3–6 months. | 0.5 mg twice a day | Angiographic restenosis | After 6 months lesions had restenosed to 47% of lumen diameter narrowing in the placebo group, and 46% in colchicine group. | Colchicine was ineffective for preventing restenosis after coronary angioplasty. | [35] |
| Deftereos et al. |
Receiving Colchicine (n = 100) Placebo (n = 96) |
Diabetic patients with the contraindication of drug-eluting-stent, undergoing PCI with a BMS (n = 196), followed up for 6 months. | 0.5 mg twice a day. | Angiographic ISR and IVUS-ISR | Lower rate of angiographic ISR in colchicine treatment group (16%: 33%; P = 0.007). IVUS-ISR is similar in two groups. Less lumen area loss in colchicine group (1.6 mm2: 2.9 mm2; P = 0.002) | Colchicine is helpful in reducing ISR rate in diabetic patients after PCI with a BMS. | [40] |
| Heart failure and myocardial infarction | |||||||
| Deftereos et al. |
Receiving Colchicine (n = 140) Placebo (n = 139) |
Patients (n = 267) with stable NYHA I-III HF symptoms with LVEF ≤ 40%, followed up for 6 months. | 0.5 mg twice daily | The proportion of patients achieving at least one-grade improvement in NYHA functional status classification |
The endpoint occurring in colchicine group is 14%, but 11% in control group. Higher rate of hospitalization from heart failure and death in colchicine group (10.1%: 9.4%; P = 0.839) |
Colchicine treatment in patient with stable CHF does not affect the likelihood of hospitalization from heart failure and death. | [177] |
| Deftereos et al. |
Receiving Colchicine (n = 77) Control (n = 74) |
Patients (n = 151) with STEMI (<12 h), followed up for 5 days | Initially 1.5 mg plus 0.5 mg after 1 h and continuing with 0.5 mg twice daily | The area under the curve of creatine kinase-myocardial brain fraction concentration | Colchicine decreases the infarct size (18.3: 23.2; P = 0.019), and the creatine kinase-myocardial brain fraction curve (3,144: 6,184; P < 0.001) | Colchicine is beneficial for ST-segment-elevation in myocardial infarction. | [45] |
| Hemkens et al. | / |
Meta-analysis 39 trials involving 4,992 patients |
/ | All-cause mortality, myocardial infarction, and adverse events | The risk for myocardial infarction was reduced (HR 0.20; 95% CI: 0.07–0.57; 2 trials) | colchicine was associated with a lower risk for MI. | [44] |
| Tardif, et al. |
Receiving Colchicine (n = 2,366) Placebo (n = 2,769) |
Patients with time of MI occurring within 30 days, followed up for 22 months. | 0.5 mg/day | MI, resuscitated cardiac arrest, coronary revascularization following urgent hospitalization for angina, and stroke. | Lower risk of endpoint shown in colchicine group (5.5%: 7.1%; P = 0.02) | Lower risk of ischemic cardiovascular event in colchicine treatment group. | [6] |
| Meng et al. |
Receiving Colchicine (n = 5,906) Control (n = 5,884) |
Meta-analysis including five trials 11,790 patients with CAD, followed up for 6–29 months |
0.5 mg once or twice daily | Major adverse cardiovascular events (MACE) | Colchicine significantly decreases the risk of MI (P = 0.04) | Colchicine is beneficial to patients with CAD for reducing the risk of cardiovascular events. | [47] |
| Shah et al. |
Receiving Colchicine (n = 206) Placebo (n = 194) |
Patients referred for possible PCI (n = 400) | 1.2 mg 1–2 h before coronary angiography, followed by colchicine 0.6 mg 1 h later or immediately before PCI | PCI-related myocardial injury. | No difference of PCI-related myocardial injury (57.3%: 64.2%; P = 0.19). Composite outcome of death, target vessel revascularization, nonfatal myocardial infarction at 30 day did not differ in two groups Preprocedural colchicine reduces the increase in IL-6 and hsCRP after PCI. | Preprocedural colchicine reduces the increase of IL-6 and hsCRP, but does not decrease the PCI-related myocardial injury risk. | [173] |
| Abrantes et al. |
Receiving Colchicine (n = 6,230) Control (n = 6,144) |
Meta-analysis 314 articles involving 12,374 patients with CAD |
≤ 1.5 mg/day colchicine | Cardiovascular mortality and major adverse cardiac events. | No difference in cardiovascular mortality (HR: 0.79; 95% CI: 0.53–1.18), but lower risk of major adverse cardiac events in colchicine group. Colchicine reduced the risk of ACS (lower 36% risk) and stroke events (51% risk) | Colchicine is beneficial for patients with CAD on prognosis. | [48] |
| Cardiovascular complications of COVID-19 | |||||||
| GRECCO-19 Deftereos et al. |
Receiving Colchicine (n = 56) Control (n = 54) |
Colchicine effect on COVID-19 patients (n = 105), followed up for 3 weeks. | 1.5 mg loading dose plus 0.6 mg after 1 h and 0.5 mg twice a day maintenance dose. | Level of hs-cardiactroponin; time to grade 7 clinical deterioration 2 points; time for C-active protein reaching over 3 times upper than reference limit. | Lower rate of endpoint in colchicine treatment group (1.8%: 14.0%; P = 0.02). Event-free survival time was longer in colchicine group (20.7 d: 18.6 d; P = 0.03) | Colchicine significantly improved the time to clinical deterioration | [51] |
|
COLCORONA Tardif et al. |
Receiving Colchicine (n = 2,235) Placebo (n = 2,253) |
Colchicine effect on COVID-19 patients (n = 4,488), followed up for 30 days. | First three days: 1 mg colchicine in two doses; after the first three days and for the consecutive 27 days: 0.5 mg/day | The combination of hospital admission or death for COVID-19. | Lower rate of primary endpoint in colchicine group (4.7%: 5.8%; P = 0.08). Among the 4,159 of patients with COVID-19 confirmed by PCR, the risk of primary endpoint is 4.6 in colchicine group (4.6%: 6.0%; P = 0.04) | Colchicine decreased the composite rate of hospitalization and death in non-hospitalized patients. | |