Colchicine Use Is Associated with Shorter Intensive Care Unit Stay and Lower Fresh Frozen Plasma Transfusion Requirements After Coronary Artery Bypass Grafting

1. Introduction

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is estimated to account for more than 22 million deaths by 2030 [1]. Coronary heart disease (CHD) is a major contributor to CVD-related mortality and morbidity, followed by stroke [1]. Ischemic heart disease (IHD) alone is one of the leading causes of death worldwide, second only to neonatal disorders [2]. Myocardial infarction (MI) is the most important clinical manifestation of CHD and one of the leading causes of death and disability worldwide [3].

Revascularization has become a major treatment modality for both acute and chronic CHD [4,5]. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are both widely accepted revascularization strategies for patients with CHD [4,5,6]. Although revascularization is important and often essential, it should be complemented by pharmacological treatments, including antiplatelet and lipid-lowering therapies [4,5]. Furthermore, anti-inflammatory agents such as colchicine are currently included in guideline recommendations, particularly for patients with atherosclerotic CHD [4,5].

In 2019, the Colchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated that low-dose colchicine was associated with a lower risk of cardiovascular complications in patients with a history of MI [7]. In 2020, the Low-Dose Colchicine 2 (LoDoCo2) trial showed that low-dose colchicine was associated with improved cardiovascular outcomes in patients with chronic CHD [8]. Subsequently, colchicine was incorporated into the medical treatment of selected patients undergoing perioperative management for CABG. Moreover, studies have demonstrated the anti-inflammatory effects of colchicine in patients undergoing CABG, primarily through improvements in biochemical parameters [9,10,11].

However, few studies have investigated the effects of colchicine on clinical outcomes and postoperative morbidity. Our study aimed to address this gap in the literature. In this retrospective study, we evaluated total length of hospital stay, length of intensive care unit stay, the numbers of erythrocyte and fresh frozen plasma transfusions, age, sex, wound infection, surgical revision, and routinely measured inflammatory parameters on postoperative day 5, including C-reactive protein (CRP), white blood cell count, albumin, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio. These parameters were analyzed and compared between patients who received colchicine and those who did not.

2. Material and Methods

This retrospective clinical study was approved by the Scientific Research Ethics Committee of the University of Health Sciences, Erzurum City Hospital (decision no. 2025/05-134) and was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study included patients who underwent elective on-pump coronary artery bypass grafting (CABG) performed by the same surgical, anesthesia, perfusion, and intensive care unit (ICU) teams.

Seventy patients who underwent CABG during the one-year period from October 2021 to October 2022 were randomly selected and constituted the control group. These patients did not receive perioperative colchicine treatment. Beginning in September 2023, based on contemporary guidelines and the available literature, colchicine was incorporated into the routine perioperative medical treatment of patients undergoing CABG in the Department of Cardiovascular Surgery at Erzurum City Hospital. Colchicine was administered orally at a dose of 0.5 mg once daily for three days before surgery and ten days after surgery, in addition to standard antiplatelet and lipid-lowering therapy. Eighty-one patients who underwent CABG during the one-year period from January 2024 to January 2025 were randomly selected and constituted the colchicine group.

Demographic, clinical, and laboratory data were retrospectively obtained from archived medical records and the hospital’s electronic information system. The collected variables included age, sex, total length of hospital stay, length of ICU stay, number of units of erythrocyte suspension and fresh frozen plasma transfused, surgical wound infection, and the need for surgical revision. Routinely measured inflammatory and laboratory parameters obtained on postoperative day 5 were also recorded, including C-reactive protein (CRP), white blood cell count, serum albumin level, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio.

Patients who underwent off-pump CABG or emergency surgery were excluded. Additional exclusion criteria were in-hospital mortality, renal failure, hepatic failure, the use of an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO), and the need for an additional surgical procedure because of cannulation-related complications. Patients requiring prolonged postoperative mechanical ventilation were also excluded. After the eligibility criteria had been applied, patients were randomly selected from the hospital’s archived medical records and electronic database.

All CABG procedures were performed through a median sternotomy under general anesthesia by the same surgical and anesthesia teams. Cardiopulmonary bypass was established in all patients using standard aortic and right atrial cannulation. Myocardial protection was achieved using antegrade administration of Del Nido cardioplegia directly into the aortic root. All procedures were performed with the same perfusion team. Complete surgical revascularization was performed according to the distribution of clinically significant coronary artery stenoses identified on preoperative coronary angiography. Following surgery, all patients were transferred to the cardiovascular surgery ICU and were extubated on the day of surgery. Patients who could not be extubated on the day of surgery were excluded.

3. Statistical Analysis

Statistical analyses were performed using IBM SPSS 26.0 Statistics for Windows (IBM Corp., Armonk, NY, USA). The analysis included 151 patients, comprising 81 patients who received colchicine (colchicine group) and 70 who did not (control group). Missing observations were handled by available-case analysis; accordingly, the denominator was allowed to vary by variable. No imputation was performed. All statistical tests were two-sided, and a P value <0.05 was considered statistically significant. Because the analyses were exploratory and no multiplicity-adjustment procedure was specified in the source analysis, P values were not adjusted for multiple comparisons.

Continuous variables were summarized as mean ± standard deviation (SD), whereas categorical variables were presented as number and percentage. Between-group comparisons of continuous variables were performed using the independent-samples Student’s t test. Homogeneity of variances was assessed using Levene’s test. When Levene’s test indicated unequal variances (P<0.05), Welch’s t test with Satterthwaite-adjusted degrees of freedom was reported; otherwise, the equal-variance Student’s t test was used. Between-group mean differences are reported as colchicine minus control values, together with 95% confidence intervals (CIs).

Categorical variables were compared using Pearson’s chi-square test when expected cell frequencies were adequate. Fisher’s exact test was used when the assumptions of the chi-square test were not met. Exploratory sex-stratified comparisons within each treatment group were performed using independent-samples t tests with the same variance-selection procedure. Associations among continuous variables were evaluated separately in the colchicine and control groups using Pearson’s product–moment correlation coefficients with pairwise deletion of missing observations. Correlation coefficients (r) and two-sided P values are reported.

4. Results

A total of 151 patients were included: 81 in the colchicine group and 70 in the control group. Age was available for 80 patients in the colchicine group and all 70 controls. The groups were similar with respect to age (62.73±8.94 vs 63.60±10.34 years; mean difference, −0.88 years; 95% CI, −3.99 to 2.24; P=0.579) and sex distribution (male: 85.0% vs 74.3%; P=0.102).

The mean intensive care unit stay was significantly shorter in the colchicine group than in the control group (4.28±1.95 vs 5.83±3.04 days). Because variances were unequal, Welch’s t test was used (t=−3.65, df=114.34; mean difference, −1.54 days; 95% CI, −2.38 to −0.71; P<0.001). Total hospital stay was numerically longer in the colchicine group, but the difference did not reach statistical significance (27.10±8.66 vs 24.53±8.13 days; mean difference, 2.57 days; 95% CI, −0.14 to 5.28; P=0.063). (Table 1)

Fresh frozen plasma requirements were markedly lower in the colchicine group (3.49±1.24 vs 8.13±3.97 units). Welch’s t test demonstrated a mean between-group difference of −4.63 units (95% CI, −5.62 to −3.65; t=−9.39, df=80.58; P<0.001). In contrast, erythrocyte transfusion requirements did not differ significantly between groups (5.49±2.70 vs 5.89±2.85 units; mean difference, −0.39 units; 95% CI, −1.28 to 0.50; P=0.387). (Table 1)

On postoperative day 5, the colchicine group had a significantly lower white blood cell count than the control group (9.44±3.31 vs 10.78±4.04×10⁹/L; mean difference, −1.34×10⁹/L; 95% CI, −2.52 to −0.16; P=0.027). No significant between-group differences were observed in C-reactive protein, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, or albumin (all P>0.05). (Table 1)

Wound infection occurred in 19 patients (23.5%) in the colchicine group and 26 (37.1%) in the control group. Although the absolute rate was lower with colchicine, the difference did not reach statistical significance (χ²=3.36, P=0.067). Surgical revision rates were comparable (6.2% vs 5.7%; Fisher’s exact P=1.000). (Table 2)

Within-group exploratory comparisons showed no statistically significant sex-based differences in any continuous outcome or postoperative laboratory parameter in either the colchicine or control group when the variance-selection rule specified above was applied (all P>0.05). These findings should be interpreted cautiously because the female subgroups were small (n=12 in the colchicine group and n=18 in the control group). (Table 3)

In the colchicine group, intensive care unit stay correlated positively with total hospital stay (r=0.472, P<0.001), erythrocyte transfusion (r=0.500, P<0.001), and fresh frozen plasma transfusion (r=0.335, P=0.002), and inversely with albumin (r=−0.282, P=0.011). Total hospital stay correlated positively with erythrocyte transfusion (r=0.470, P<0.001), fresh frozen plasma transfusion (r=0.304, P=0.006), and CRP (r=0.399, P<0.001), and inversely with albumin (r=−0.389, P<0.001). Erythrocyte and fresh frozen plasma transfusion requirements were positively correlated (r=0.529, P<0.001). Erythrocyte transfusion was inversely correlated with albumin (r=−0.455, P<0.001). (Table 4)

In the control group, intensive care unit stay correlated positively with total hospital stay (r=0.550, P<0.001), erythrocyte transfusion (r=0.252, P=0.035), fresh frozen plasma transfusion (r=0.260, P=0.030), WBC (r=0.429, P<0.001), and NLR (r=0.401, P<0.001), and inversely with albumin (r=−0.253, P=0.035). Erythrocyte and fresh frozen plasma transfusion requirements were positively correlated (r=0.486, P<0.001); both were inversely correlated with albumin (r=−0.419, P<0.001 and r=−0.457, P<0.001, respectively). (Table 5)

5. Discussion

The autumn crocus plant was used to treat swelling and pain in ancient Egypt and ancient Greece [12]. Galen of Pergamon (modern-day İzmir, Türkiye), the renowned Roman physician from Anatolia, mentioned the use of colchicine for the treatment of gout [12]. Another Anatolian physician, Alexander of Tralles (modern-day Aydın, Türkiye), was the first to describe the gastrointestinal side effects of colchicine during the Byzantine period [12]. From its historical use to the present day, colchicine has been derived from the autumn crocus plant and has traditionally been used in the treatment of gout and familial Mediterranean fever (FMF) [13]. Furthermore, colchicine is used to treat inflammatory and fibrotic conditions such as Behçet’s disease (BD) and pericarditis [13]. The primary mechanism of action of colchicine involves the inhibition of microtubule polymerization [13]. Microtubules play important roles in chemokine and cytokine secretion, intracellular trafficking, and cell migration [13]. Furthermore, colchicine exerts its anti-inflammatory effects through several mechanisms, including the inhibition of inflammasome activation and interleukin-1 beta (IL-1β) production, as well as the suppression of neutrophil functions [13]. Colchicine has gradually become an integral component of pericarditis treatment, and its addition to conventional therapy provides clinical benefits, including lower recurrence rates [14]. Therefore, according to current guidelines, colchicine is included in the conventional treatment of both acute and recurrent pericarditis [15,16].

In 2013, Nidorf et al. [17] demonstrated in the Low-Dose Colchicine (LoDoCo) trial that low-dose colchicine was beneficial in reducing the risk of cardiovascular complications in patients with stable CHD. They proposed that colchicine targets inflammation within unstable atherosclerotic plaques [17]. In 2019, Tardif et al. [7] showed in the COLCOT trial that colchicine was associated with fewer cardiovascular events in patients with a history of MI, without altering biochemical inflammatory markers. Subsequently, Nidorf et al. [8] reported the results of the LoDoCo2 trial. Although routine inflammatory markers were not assessed, their study confirmed that low-dose colchicine was associated with fewer cardiovascular events in patients with chronic CHD [8]. In contrast, Tong et al. [18] reported opposing results in patients with acute CHD who received colchicine during a 12-month follow-up period. Their findings indicated that colchicine provided no clinical benefit over 12 months and that patients receiving colchicine had higher mortality rates [18]. Nevertheless, colchicine is still not recommended as a conventional medication for secondary prevention after CABG [19]. However, the latest American Heart Association (AHA) guideline, consistent with European guidelines, recommends low-dose colchicine for patients with acute CHD [4,5,20].

Nevertheless, particularly following its inclusion in guidelines for the treatment of CHD, the literature on the relationship between colchicine and CABG has begun to expand. In contrast to Tardif et al. [7], Pan et al. [11] demonstrated that colchicine was associated with lower levels of inflammatory markers. However, Tardif et al. [7] s investigated patients with a history of MI, whereas Pan et al. [11] studied patients who underwent CABG. In this context, colchicine may attenuate surgery-related inflammation. For instance, our study was conducted in patients who underwent CABG, and WBC counts were significantly lower in the colchicine group. Regarding inflammation, our findings appear to be consistent with those reported by Pan et al. [11]. They also demonstrated that colchicine was associated with improved cardioprotection, as indicated by lower postoperative CK-MB and troponin levels [11]. Furthermore, their study included a broader and more comprehensive range of inflammatory markers, such as IL-6 and procalcitonin [11]. The assessment of these markers was not feasible in our study because of its retrospective design. Therefore, we focused on routinely measured inflammatory markers, including CRP, WBC, NLR, NLP, and albumin. Colchicine was associated with lower WBC counts. However, none of the other inflammatory markers differed significantly between the groups in our study.

Diakova et al. [10] reported that colchicine use was associated with lower levels of inflammatory markers, such as IL-10 and IL-6. In contrast, TNF-α and IL-1β levels did not differ significantly between the two groups. Their study also evaluated clinical complications, including pneumonia, sternal wound infections, and early postoperative bleeding [10]. Interestingly, pneumonia and wound infections were more common in the colchicine group, although the differences were not statistically significant [10]. However, the rate of early postoperative bleeding was significantly lower in the colchicine group [10]. In this regard, their findings appear to contrast with ours. Although the differences were not statistically significant, wound infections and the need for surgical revision were less frequent in the colchicine group in our study. However, the range of inflammatory markers assessed in our study was limited, as inflammation was evaluated using only routinely measured parameters. Therefore, we assessed systemic inflammation using the systemic immune-inflammation index (SII), calculated from complete blood count parameters, as a cost-effective and useful approach [21]. Although the differences were not statistically significant, NLR and PLR values were lower in the colchicine group.

Colchicine has other beneficial effects in patients undergoing CABG. Ponnana et al. [22] suggested that colchicine may reduce cardiovascular events and the incidence of atrial fibrillation (AF) after CABG. Diakova et al. [23] confirmed these findings regarding postoperative AF. Farzaneh et al. [24] also reported beneficial effects of colchicine in preventing AF after CABG. However, we were unable to assess postoperative AF because of the difficulty in accessing the relevant medical records. Despite the limitations of our study, our findings have not previously been reported in the literature. Colchicine use was associated with lower fresh frozen plasma transfusion requirements and shorter ICU stays, both of which are important clinical outcomes in patients undergoing CABG.

6. Conclusions

Perioperative low-dose colchicine use was associated with a shorter ICU stay, lower fresh frozen plasma transfusion requirements, and reduced postoperative WBC counts in patients undergoing elective on-pump CABG. These findings suggest that colchicine may attenuate the postoperative inflammatory response and contribute to improved early clinical outcomes following surgical revascularization. However, colchicine use was not associated with significant differences in total hospital stay, erythrocyte transfusion requirements, CRP, NLR, PLR, albumin levels, wound infection rates, or the need for surgical revision. Although wound infections were numerically less frequent in the colchicine group, this difference did not reach statistical significance.

The observed reductions in ICU stay and fresh frozen plasma requirements represent clinically relevant findings that have not been extensively addressed in previous studies of colchicine in patients undergoing CABG. Nevertheless, given the retrospective design, relatively small sample size, noncontemporaneous study groups, and limited availability of detailed inflammatory and postoperative clinical data, these findings should be regarded as hypothesis-generating rather than evidence of a causal relationship. Further large-scale, prospective, randomized controlled trials are required to confirm these results, clarify the underlying mechanisms, and determine whether perioperative colchicine should be incorporated into routine treatment protocols for patients undergoing CABG.