The Effect of Colchicine on Platelet Function Profiles in Patients with Stable Coronary Artery Disease: The ECLIPSE Pilot Study

Abstract

Introduction

This prospective, single-arm pharmacodynamic study assessed the effect of colchicine (COLC) [Strides Pharma UK Ltd, Watford, Hertfordshire, England] 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs).

Methods

Twenty-two patients with stable coronary artery disease (CAD) on dual antiplatelet therapy (DAPT) with daily maintenance aspirin and clopidogrel were recruited. Baseline platelet function was evaluated with the VerifyNow™ ARU and PRU assays (Werfen, Bedford, MA, USA) and assessed post-completion of COLC 0.5 mg once daily for 14 days.

Results

In this study, the median ARU baseline score was 463, and post-COLC it was 436, which was not statistically significant (p = 0.485). The mean difference in scores was −18.31 (95% confidence interval [CI] −74.34 to 37.71, p = 0.504). At baseline, 27.3% of the patients had “aspirin resistance” or were non-responders, compared to 13.6% post-COLC (p = 0.423). The median baseline PRU score was 210, and post-COLC it was 199, which was also not statistically significant (p = 0.581). The mean difference in scores was −7.31 (95% CI −31.1 to 16.5, p = 0.530). At baseline, 50% of the patients had “clopidogrel resistance” or were non-responders, compared to 45.5% post-COLC (p = 0.999). Two patients experienced mild gastrointestinal upset during the trial without interruption of COLC, and there were no serious adverse events or treatment-emergent adverse events.

Conclusions

There were no significant differences in ARUs and PRUs post-COLC trial in patients with stable CAD. This pilot pharmacodynamic study could be clinically informative in patients on DAPT. Further studies are required to confirm these exploratory findings.

Trial registration

ClinicalTrials.gov identifier, NCT06567678, prospectively registered 20/8/2024.

Key Summary Points

Why carry out this study?

Coronary artery disease (CAD) is the leading cause of cardiovascular disease (CVD) mortality per capita worldwide, followed by hemorrhagic and ischemic stroke.

Accentuated platelet reactivity with respect to both aspirin and clopidogrel resistance or non-responsiveness may be implicated in increased major adverse cardiovascular events (MACE).

Low-dose colchicine (COLC), an anti-inflammatory drug, reduces MACE by 25% to 30% in patients with CVD. The mechanism for this needs to be better elucidated. In vitro, COLC inhibits many conventional platelet functions, such as aggregation, albeit at supraphysiological concentrations.

What was learned from the study?

There were no significant differences in aspirin reaction units or P2Y12 reaction units post-COLC trial.

This dedicated pharmacodynamic study could potentially be informative and applicable in patients with stable CAD on dual antiplatelet therapy.

Introduction

Coronary artery disease (CAD) is the leading cause of cardiovascular disease (CVD) mortality per capita worldwide, followed by hemorrhagic and ischemic stroke. Global CVD-related mortality rose from above 12 million in 1990 to almost 20 million in 2022, reflecting the growing and aging society with its attendant metabolic and environmental risks complicated by regional socioeconomic and healthcare system factors [1, 2].

Accentuated platelet reactivity with respect to both aspirin and clopidogrel resistance or non-responsiveness may negatively predict major adverse cardiovascular events (MACE) [3–5]. The US Food and Drug Administration (FDA) has recently approved colchicine (COLC) 0.5 mg as the first anti-inflammatory therapy indicated for reducing MACE in patients who have established CVD or are susceptible [6, 7]. Low-dose COLC reduces MACE by 25–30% in patients with CVD [8]. The mechanism for this needs to be better elucidated. In vitro, COLC inhibits many typical platelet functions; however, many of these effects were reported at apparently supraphysiological concentrations [9–12].

We conducted this exploratory pilot study to assess the antiplatelet pharmacodynamic effect of COLC on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs) in patients with stable CAD on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel.

Methods

Study Design and Patient Population

The study complied with the Declaration of Helsinki, International Conference on Harmonization, Good Clinical Practice (ICH-GCP), and was authorized by the Campus Research Ethics Committee (CREC) of the University of the West Indies, St. Augustine (UWI STA), Trinidad (CREC-SA.2525/02/2024) [13, 14]. All patients with stable CAD on DAPT consented (written, triplicate) to participate in a prospective, open-label, single-arm pharmacodynamic study that evaluated the effect of COLC (Strides Pharma UK Ltd, Watford Hertfordshire, England) 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to ARUs and PRUs. Patients were recruited between August 2024 and September 2024 at the ambulatory outpatient clinic, Trinidad Institute of Medical Technology (TIMT), Trinidad and Tobago. They met selection criteria if they were legal adults above 18 years of age and were awaiting either elective percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on maintenance aspirin and clopidogrel. The study’s exclusion criteria comprised recent acute coronary syndrome (ACS) within 6 months, active hemorrhage, history of intracerebral stroke, cardiogenic shock or lethal arrhythmia post-index event, prescribed oral anticoagulants such as coumarin derivatives, direct thrombin inhibitors, or factor X inhibitors, platelet count < 100 × 10⁶/mL, hemoglobin < 10 g/dL, serum creatinine > 1.5 mg/dL, and patients on hepatic cytochrome CYP 2C19 and CYP 3A enzyme inhibitors or inducers. After completing the study, patients were followed up for 28 days post-procedure to assess whether they experienced any serious adverse events or treatment-emergent adverse events (Fig. 1).

Fig. 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram

Blood Sampling and VerifyNow™ ARU and P2Y₁₂ Testing

The platelet function assays utilized were the VerifyNow™ ARU assay and the PRU assay (Werfen, Bedford, MA, USA). The assays were performed according to standard protocols, as described previously [3, 4, 15]. An ARU ≥ 550 was considered “aspirin resistance” during treatment with a maintenance dose of 81 mg [3, 16, 17]. A PRU > 208 was considered indicative of “clopidogrel resistance” or high on-treatment platelet reactivity (HPR) according to the most recent consensus [18, 18].

Aspirin and clopidogrel were not administered on the morning of the patients’ fasting scheduled visit (8:00 a.m. to 9:00 a.m.; 18–24 h prior to blood sampling), which assessed trough levels. Venipuncture was performed using a 21-gauge needle (Greiner Bio-One North America, Monroe, NC, USA, #450097) and sequestered into a Vacuette (Greiner Bio-One North America) blood collection tube containing 3.8% trisodium citrate (#454322) after disposing of 5 mm of waste. These collected blood samples were processed by blinded laboratory personnel who were unaware of the ongoing study intervention. VerifyNow™ ARU and PRU assays (Werfen, Bedford, MA, USA) were utilized in accordance with standardized protocols.

The enrolled patients were then treated with COLC (Strides Pharma UK Ltd, Watford Hertfordshire, England) 0.5 mg administered orally once daily for 14 days, with accountability by the clinical research associate. They received their final dose of COLC on day 14 without aspirin and clopidogrel and were subsequently tested with both assays at their fasting scheduled visit (8:00 a.m. to 9:00 a.m.). Platelet reactivity was then reassessed with both assays using the aforementioned methodologies (see Fig. 1).

Patient Interview and Case Report Form

The patients’ demographic data were transcribed on a case report form (CRF). They included the patient’s age, gender, ethnicity, anthropometric data, respective ARUs and PRUs on COLC, and adverse drug reactions, including gastrointestinal upset (nausea, vomiting, diarrhea) and hematologic (cytopenia) and dermatologic sequelae (rash, drug-related skin eruption).

Statistical Analysis

The calculated sample size was 22 patients based on a paired proportion sample, an alpha (α) value of 0.05, power of 90%, estimated baseline PRU of 217.25 from the EFFECT pilot study, and an anticipated delta of −10% with respect to PRUs [15, 19]. The collected data were analyzed using descriptive statistics as well as the Statistical Package for the Social Sciences (SPSS version 28.0) software for statistical analysis. Descriptive data are presented using frequencies with percentages for categorical variables, means for continuous data, and medians for non-normal data. Given the small sample size, Shapiro–Wilk tests were performed to determine data normality. Pairwise comparisons were made using McNemar’s test for paired proportions and the Wilcoxon signed-rank test for non-normal scores. Mean differences were calculated with 95% confidence limits. A p value of < 0.05 was used to indicate statistical significance. All participants were 100% compliant with administration of both study drugs, verified with pill accountability, and completed this study without any protocol deviations.

Results

Of a total of 22 patients, the average age was almost 62 years, with close to 55% representing the female gender. Caribbean South Asians comprised nearly 73%, with Caribbean Blacks 23% and mixed and/or interracial 5% of the study population. The mean body mass index (BMI) was 28.6 (standard deviation [SD] ± 5.6 kg/m²) (Table 1). The prevalence of the patients’ predominant comorbidities included 22.7% with prior percutaneous coronary intervention (PCI), 18.2% with prior CABG surgery, 77.3% with hypertension, 81.8% with diabetes, 63.6% with dyslipidemia, and 22.7% with obesity (Table 1). With respect to common cardiovascular medications, 95.5% were on high-intensity statin, therapy, 72.7% on angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor blocker/neprilysin inhibitors (ACEi, ARB, ARNi) and 63.6% on beta-blockers (βB) (Table 1).

Table 1.

Patients’ demographic, medical, and procedural history and cardiovascular medication information

Demographic characteristic	Value, frequency (%)
Age (years)a	61.86 ± 7.33
Genderb
Female	12 (54.5%)
Male	10 (45.5%)
Ethnicityb
Caribbean South Asian	16 (72.7%)
Caribbean Black	5 (22.7%)
Interracial/mixed	1 (4.5%)
Body mass index (BMI)a	28.63 ± 5.58
Diagnosis	Frequency (%)
Coronary artery disease (CAD)	22 (100%)
Percutaneous coronary intervention (PCI)	5 (22.7%)
Coronary artery bypass graft (CABG)	4 (18.2%)
Heart failure with reduced ejection fraction (HFrEF)
No	21 (95.5%)
Yes	1 (4.5%)
Type 2 diabetes mellitus (T2DM)
No	5 (22.7%)
Yes	17 (77.3%)
Hypertension (HTN)
No	4 (18.2%)
Yes	18 (81.8%)
Hyperlipidemia (HLD)
No	8 (36.4%)
Yes	14 (63.6%)
Cerebrovascular event (CVE)
No	20 (90.9%)
Yes	2 (9.1%)
Chronic kidney disease (CKD)
No	20 (90.9%)
Yes	2 (9.1%)
Chronic obstructive pulmonary disease (COPD)
No	22 (100.0%)
Peripheral artery disease (PAD)
No	21 (95.5%)
Yes	1 (4.5%)
Obesity
No	17 (77.3%)
Yes	5 (22.7%)
Cardiovascular medications	Frequency (%)
Aspirin	22 (100.0%)
Clopidogrel	22 (100.0%)
High-intensity statin (HIS)	21 (95.5%)
Angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, angiotensin receptor blocker/neprilysin inhibitor (ACEi, ARB, ARNi)	16 (72.7%)
Beta-blocker (BB)	14 (63.6%)
Metformin (MET)	8 (36.4%)
Sodium-glucose cotransporter-2 inhibitor (SGLT2i)	6 (27.3%)
Calcium channel blocker (CCB)	5 (22.7%)
Nitrates	5 (22.7%)
Trimetazidine (TMZ)	4 (18.2%)
Sulfonylureas (SUs)	3 (13.6%)
Insulin (INS)	2 (9.1%)
Mineralocorticoid receptor antagonist (MRA)	2 (9.1%)
Dipeptidyl peptidase-4 inhibitor (DPPIVi)	1 (4.5%)
Glucagon-like peptide-1 receptor agonist (GLP1-RA)	0 (0.0%)
Ivabradine (IVB)	0 (0.0%)

^aMean ± standard deviation (SD)

^bFrequency (percentage, %)

In this study, the median ARU baseline score was 463, and post-COLC it was 436, which was not statistically significant (p = 0.485). The mean difference in scores was −18.31 (95% confidence interval [CI] −74.34 to 37.71, p = 0.504) (Table 2, Fig. 2). At baseline, 27.3% of the patients had “aspirin resistance” or were non-responders, compared to 13.6% post-COLC (p = 0.423). The median baseline PRU score was 210, and post-COLC it was 199, which was also not statistically significant (p = 0.581). The mean difference in scores was −7.31 (95% CI −31.1 to 16.5, p = 0.530) (Table 2, Fig. 2). At baseline, 50% of the subjects demonstrated “clopidogrel resistance” or were non-responders, compared to 45.5% post-COLC (p = 0.999). Two patients experienced mild gastrointestinal upset during the trial without interruption of COLC, and there were no serious adverse events or treatment-emergent adverse events.

Table 2.

Comparison of patients’ median aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs), mean differences, and resistance percentages at baseline and post-colchicine (COLC) 0.5 mg trial after 14 days

Variable	Baseline	Post-colchicine (COLC)	p value
Aspirin reaction units (ARUs)
Median ARUs	463	436	0.485
Mean difference	−18.31 (95% CI −74.34 to 37.71)		0.504
“Aspirin resistance” or non-responders	27.3%	13.6%	0.423
P2Y12 reaction units (PRUs)
Median PRUs	210	199	0.581
Mean difference	−7.31 (95% CI −31.1 to 16.5)		0.530
“Clopidogrel resistance” or non-responders	50%	45.5%	0.999

Fig. 2.

Comparison of patients’ aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs). A The patients’ ARUs at baseline and their transition during the 14-day course of colchicine (COLC) 0.5 mg once daily did not meet statistical significance. B The patients’ PRUs at baseline and their transition during the 14-day course of COLC 0.5 mg once daily did not meet statistical significance

Discussion

COLC, an anti-inflammatory alkaloid, is now a pivotal therapy in the management of cardiovascular inflammation [20]. COLC recently gained traction as an emerging therapy as an anti-inflammatory agent following the 2019 Colchicine Cardiovascular Outcomes Trial (COLCOT), which demonstrated a 1.6% absolute reduction in major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS) [21]. In patients with chronic coronary syndrome (CCS), as per the Low-dose Colchicine 2 (LoDoCo 2) Trial, COLC similarly reduced MACE over a median follow-up of 28.6 months [22]. These two landmark trials were crucial in its regulatory approval by the FDA, being labeled as the first targeted anti-inflammatory drug for CAD [6, 23]. Several systematic reviews have summarized the available evidence on COLC for both ACS and CCS, with a recent meta-analysis pooling data from all of the major trials alluding to a 32% reduction in MACE among patients treated with COLC [24–26]. Despite this evidence, COLC has not been shown to confer any survival benefit in these trials, and its net risk–benefit profile requires further investigation [27, 28].

COLC primarily inhibits microtubule assembly but also demonstrates myriad other mechanistic effects, such as inhibiting a complex and intricate milieu comprising (1) endothelial cell dysfunction and inflammation, (2) smooth muscle cell proliferation and migration, (3) macrophage chemotaxis, migration, and adhesion, and (4) platelet activation. At lower doses, it inhibits microtubule dynamics and cell migration, while at higher doses, it impedes cell division [28]. COLC also impedes the translocation of tissue factor via cytoskeletal tracks associated with the microtubule arrays, along with other intracellular traffic of secreted and transmembrane proteins in vesicles [28].

On a molecular basis, it also attenuates proinflammatory cytokine release. It inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation, the latter of which is crucial in cell repair [29]. COLC also mitigates intracellular transport of the adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (CARD), attenuating the release of interleukin-1β, which is a pivotal cytokine involved in the network of immune inflammation linked to CAD [28]. COLC has stable interaction with the adenosine triphosphate (ATP) binding pocket of the neuronal apoptosis inhibitor protein (NAIP), which can decrease pore formation and ATP-mediated NLRP3 inflammasome activation [28]. Physiological concentrations of COLC inhibit collagen- and calcium ionophore-induced platelet aggregation and internal signaling [9]. Many of these in vitro studies demonstrated COLC effects on platelet function only at supraphysiological concentrations.

This study assessed whether there were any pleiotropic effects on platelet reactivity in patients with stable CAD on DAPT using 0.5 mg of COLC once daily for 14 days. The VerifyNow™ (VN) (Werfen, Bedford, MA, USA) is a rapid, commonly used point-of-care analyzer that determines platelet reactivity by assessing light transmittance induced by platelet aggregation in response to specific agonists [30, 31]. Some agonists that are crucial in platelet aggregation pathways include thrombin, collagen, serotonin, adenosine diphosphate (ADP), and thromboxane A2 (TXA2). Aspirin and clopidogrel are both cornerstone antiplatelet therapies in the management of CAD and block the formation of TXA2- and P2Y₁₂-mediated ADP stimulation, respectively [32]. The P2Y₁ receptor affects platelet morphology with transient aggregation, whereas the P2Y₁₂ receptor is integral in the cascade amplification of platelet aggregation and thrombus stabilization [33].

In a mechanistic study by Cirillo et el., platelets from 35 patients with stable CAD on DAPT were pre-incubated with COLC 10 µM before being stimulated with ADP 20 µM or thrombin receptor activating peptide (TRAP) 25 µM at several time points (0, 30, 60 and 90 min) to assess maximal aggregation by light transmission aggregometry (LTA). It was observed that COLC significantly attenuated TRAP-induced platelet aggregation in both clopidogrel responders and those with HPR, with the latter subgroup also displaying a similar direction with respect to ADP-induced platelet aggregation. Overall, it was demonstrated that COLC inhibited platelet aggregation in patients with HPR despite DAPT [34]. In our study, the median ARU baseline score was 463, and post-COLC it was 436, which was not statistically significant (p = 0.485). The mean difference in scores was −18.31 (95% CI −74.34 to 37.71, p = 0.504). At baseline, 27.3% of the patients had aspirin resistance, compared to 13.6% post-COLC (p = 0.423). The median baseline PRU score was 210, and post-COLC it was 199, which was also not statistically significant (p = 0.581). The mean difference in scores was −7.31 (95% CI −31.1 to 16.5, p = 0.530). At baseline, 50% of the patients had clopidogrel resistance, compared to 45.5% post-COLC (p = 0.999). Our study’s results did not replicate the findings seen in Cirillo’s study, albeit with several caveats, as ours was an in vivo, pragmatic, real-world clinical study with a nominal COLC dose used in recent seminal trials, namely COLCOT and LoDoCo 2.

A study by Shah et al. assessed the effects of varying concentrations of COLC on platelet activity in vitro, and a clinically relevant 1.8-mg dose was administered to 10 healthy participants. It was determined that COLC addition in vitro reduced LTA aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. The administration of 1.8 mg COLC to healthy patients had no observed effect on LTA aggregation; however, it reduced the degree of MPA, NPA, platelet surface expression of PAC-1 and P-selectin, and platelet adhesion to collagen 2 h post-COLC. Overall, in clinically pertinent concentrations, COLC decreased surface expression markers and inhibited some facets of platelet aggregation. This study revealed that a nominal loading dose of COLC attenuates platelet activity with respect to platelet activation and the platelet–leukocyte interface, but may not impact platelet–platelet interactions [10]. Our study did not utilize a loading dose of 1.8 mg or variable doses, and platelet function was only assessed with respect to ARUs and PRUs, as it did not include platelet activity surface markers.

In a study performed by Raju et al., no difference was noted in platelet aggregation in response to ADP, arachidonic acid, or collagen in a subgroup of 49 patients. There was also no difference in platelet function assessed using platelet aggregation with ADP (5 μmol), arachidonic acid (0.5 mmol), collagen (1 µg/mL), and collagen (5 µg/mL), and urine dehydrothromboxane B2 [35]. This study enrolled patients with ACS and acute stroke with COLC 1 mg as the trial intervention. In contrast, our patient cohort included a stable panel of chronic coronary syndromes and adopted the FDA-approved dosage used in the milestone trials.

As mentioned earlier, COLC may, directly and indirectly, impact platelet aggregation via several pathways, including reducing platelet aggregation in response to collagen, ADP, and TRAP, inhibiting platelet degranulation and the formation of platelet-derived extracellular vesicles, reducing reactive oxygen species generation in response to glycoprotein VI stimulation, and modulating cytoskeleton rearrangement by inhibiting cofilin and LIM domain kinase 1 [9]. Based on the study results, we cannot ascertain whether COLC has any effect on these pathways, given that they were not statistically significant, and the study utilized the standard CVD dose without assessing other biochemical and physiologic parameters.

Currently, given the revitalization of COLC in the cardiovascular armamentarium, there is a paucity of in vivo clinical studies evaluating mechanistic pathways and pharmacodynamic and pharmacokinetic characteristics. The COLC–platelet interaction has the potential to attenuate MACE, but further high-fidelity studies are required [9, 36]. While this study, in addition to the studies mentioned above, did not display a robust antiplatelet effect, given their intrinsic limitations of study size, platelet function testing, COLC dosing, and clinical endpoints, it may prompt other investigators to seek alternative mechanisms or pathways of the COLC-derived mortality benefit observed in the COLCOT and LoDoCo 2 studies.

Study Limitations

This study was not primarily designed for clinical endpoints but was sufficiently powered based on ARU and PRU data from preexisting studies from our group in this Caribbean setting. Thus, the generalizability and applicability of these results may not translate to clinical effectiveness, efficacy, or safety.

As with previous studies, the vast majority of patients enrolled were of Caribbean South Asian descent, implying an inherent selection bias. This has been a recurrent feature of these clinical studies performed in this region, all hovering with near-identical ethnic proportions [4, 5, 15, 37, 38]. The same can be said of the relatively high prevalence of T2DM, approaching 80% in this study group, which is inextricably linked with accentuated platelet reactivity [39, 40].

Patients were on maintenance DAPT with aspirin and clopidogrel, and platelet function profiles on more novel and potent antithrombotic agents, such as ticagrelor and apixaban, were not evaluated. Prespecified subgroup analyses evaluating any interaction effect of other therapies with COLC were not performed, such as sodium-glucose cotransporter-2 inhibitor (SGLT2i), which can also impact platelet reactivity [15, 38]. This was due to the pilot sample size, with even smaller subgroups—for example, six patients on SGLT2i—and the concern for data dredging or mining. Employing VN as the solitary platelet function test is also a drawback, as it relies on a fixed concentration of a limited number of agonists, of which arachidonic acid is non-physiological. Ideally, assessing responses to varying concentrations of an array of physiological agonists may have proven more informative. Comprehensive platelet function testing, including flow cytometry, thromboelastography, and novel markers such as FcγRIIa, may prove informative; however, it remains unavailable in this setting due to several logistical issues [41–43]. Additionally, platelet function testing did not entail assessing other doses of COLC or several time points, as performed in the aforementioned mechanistic studies. Ideally, a large-scale, double-blind, randomized controlled trial would have been optimal; however, many challenges currently exist in implementing such a venture in a limited-resource setting.

Conclusions

No significant differences were found in ARUs and PRUs post-COLC trial in patients with stable CAD. This pilot pharmacodynamic study could be clinically informative in patients on DAPT. Further studies are required to confirm these exploratory findings.

Author Contributions

Naveen Seecheran and Kathryn Grimaldos conceptualized and designed the study. Penelope McCallum, Priya Ramcharan, Jessica Kawall, Arun Katwaroo, Gabriella Grimaldos, Valmiki Seecheran, Cathy-Lee Jagdeo, Salma Rafeeq, Rajeev Seecheran, Abel Leyva Quert, Nafeesah Ali, Lakshmipathi Peram, Shastri Motilal, Rishi Ramtahal, Neal Bhagwandass, Stanley Giddings, Anil Ramlackhansingh, and Sherry Sandy conducted the study. Kathryn Grimaldos, Priya Ramcharan, Jessica Kawall, Arun Katwaroo, Gabriella Grimaldos, Valmiki Seecheran, Cathy-Lee Jagdeo, Salma Rafeeq, Rajeev Seecheran, Abel Leyva Quert, Nafeesah Ali, Lakshmipathi Peram, Shastri Motilal, Rishi Ramtahal, Neal Bhagwandass, Stanley Giddings, Anil Ramlackhansingh, and Sherry Sandy reviewed the study. Naveen Seecheran and Kathryn Grimaldos wrote the manuscript. Naveen Seecheran revised the manuscript. The guarantor, Naveen Seecheran, accepts full responsibility for the work and the conduct of the study, has access to the data, and controls the decision to publish.

Funding

No funding or sponsorship was received for the publication of this article. The Campus Research and Publication Fund Committee, at its meeting on April 25, 2024, received our grant application and agreed to approve a grant for TT$62,595.00 (CRP.3.MAR24.10) from the Medical Sciences Funds to cover the cost of the PRU Test Kit ($35,040), the ARU Test Kit ($20,600) and the sales tax ($6955) for the project.

Data Availability

All available data can be obtained by contacting the corresponding author. ARC ClinicalTrials.gov identifier, NCT06567678, prospectively registered 20/8/2024. All materials, data, code, and associated protocols will be made promptly available to the editor and readers upon request. If requested, there will be no restrictions on the availability of materials.

Declarations

Conflict of Interest

Naveen Seecheran is an Editorial Board member of Cardiology and Therapy. Naveen Seecheran was not involved in the selection of peer reviewers for the manuscript or any of the subsequent editorial decisions. Kathryn Grimaldos, Penelope McCallum, Priya Ramcharan, Jessica Kawall, Arun Katwaroo, Gabriella Grimaldos, Valmiki Seecheran, Cathy-Lee Jagdeo, Salma Rafeeq, Rajeev Seecheran, Abel Leyva Quert, Nafeesah Ali, Lakshmipathi Peram, Shastri Motilal, Rishi Ramtahal, Neal Bhagwandass, Stanley Giddings, Anil Ramlackhansingh, and Sherry Sandy have nothing to disclose with respect to personal, financial, commercial, or academic conflicts of interest.

Ethical Approval

The study complied accordingly with the Declaration of Helsinki, International Conference on Harmonization, Good Clinical Practice (ICH-GCP), and was authorized by the Campus Research Ethics Committee (CREC) of the University of the West Indies, St. Augustine (UWI STA), Trinidad (CREC-SA.2525/02/2024). All patients with stable CAD on DAPT consented (written, triplicate) to participate in a prospective, open-label, single-arm pharmacodynamic study that evaluated the effect of colchicine (COLC) [Strides Pharma UK Limited, Watford Hertfordshire, England] 0.5 mg administered orally once daily for 14 days on platelet reactivity with respect to aspirin reaction units (ARUs) and P2Y₁₂ reaction units (PRUs).