Abstract
Background
MINOCA accounts for 5 %–15 % of myocardial infarctions and is defined by <50 % coronary stenosis without an alternative diagnosis, with heterogeneous mechanisms that complicate care. Given the role of inflammation and microvascular dysfunction, we evaluated whether colchicine improves outcomes.
Methods
We conducted a retrospective cohort study using TriNetX, a federated health research network of 134 million patients from 102 healthcare organizations. Adults (≥18 years) with a primary diagnosis of acute myocardial infarction (AMI) and no revascularization after cardiac catheterization and without alternative diagnosis of elevated troponin were classified as MINOCA according to AHA criteria. Patients with MINOCA on colchicine (≥1 year of use for any indication) were propensity score matched with patients who were not on colchicine.
Results
The primary composite outcome defined as AMI recurrence, all-cause mortality, cerebrovascular events, and all-cause hospitalizations, was significantly lower with colchicine (HR 0.839, 95 % CI 0.750–0.938, p < 0.001). Secondary outcomes of AMI recurrence (HR 0.749, 95 % CI 0.646–0.867, p < 0.001) and all-cause mortality (HR 0.518, 95 % CI 0.312–0.862, p < 0.001) were significantly lower in the colchicine group. Heart failure events (HR 0.861, 95 % CI 0.723–1.026, p > 0.05) and all-cause hospitalizations (HR 0.892, 95 % CI 0.779–1.020, p = 0.764) showed a trend toward lower rates with colchicine, which was not statistically significant. There was no difference in cerebrovascular events between the two groups (HR 1.364, 95 % CI 0.638–2.914, p = 0.820).
Conclusions
In this large real-world cohort, there was a trend toward reduced cardiovascular outcomes in patients with MINOCA who were on colchicine. These findings support further prospective evaluation of colchicine in this understudied population.
Meeting presentation
A portion of this work was presented as a poster at the 2025 American College of Cardiology Annual Scientific Session (Abstract #1047–113) on March 29, 2025, but the full manuscript and supplementary material remain unpublished. All authors have reviewed and approved the submission and report no conflicts of interest.
Keywords: Myocardial infarction, Colchicine, MINOCA, Inflammation, Cardiovascular outcomes, Retrospective studies, Propensity score, Heart failure, Coronary angiography, Anti-inflammatory agents
1. Introduction
Myocardial infarction with nonobstructive coronary arteries (MINOCA) accounts for 5–15 % of acute myocardial infarction (AMI) yet remains mechanistically diverse and clinically uncertain [1]. Unlike type 1 MI, which is typically caused by plaque rupture and thrombosis, MINOCA is a heterogeneous entity. It is defined as acute myocardial infarction, according to the Fourth Universal Definition of MI, occurring in patients with nonobstructive coronary arteries (<50 % stenosis on angiography) and no alternate clinical explanation for myocardial injury [1].
Emerging evidence suggests inflammation plays a key role in MINOCA, supported by elevated inflammatory markers that are associated with poor prognosis [2]. Such markers include the NOD-like Receptor Protein 3 (NLRP3) inflammasome, which plays a crucial role in vascular inflammation. NLRP3 activation promotes the release of IL-1β, IL-18, and IL-6, triggering endothelial dysfunction and microvascular inflammation [3]. These inflammatory markers and CRP are elevated in MINOCA [2]. Higher CRP levels are independently associated with adverse CV outcomes, including all-cause mortality and major cardiovascular events in MINOCA patients [4].
Colchicine, an NLRP3 inflammasome inhibitor, is thought to prevent neutrophil activation and reduces endothelial dysfunction. Neutrophil extracellular traps (NETs) promote microvascular occlusion and worsening ischemia [5]. By inhibiting neutrophil adhesion, migration, and NET formation, colchicine reduces microvascular thrombosis and endothelial damage [6]. Colchicine's cardiovascular (CV) benefits in patients with stable coronary artery disease (CAD) have been well established, but its efficacy in MINOCA remains unexplored. [3,7] Since microvascular dysfunction drives ischemia in MINOCA, we postulate that colchicine may potentially improve outcomes in this population by reducing inflammatory signaling and restoring endothelial function [8].
2. Methods
We used TriNetX, a federated health research network providing access to electronic health record (EHR) statistics from approximately 134 million patients across 102 healthcare organizations, mainly in the United States. TriNetX received a Western IRB waiver as it only aggregated de-identified data without handling protected health information or performing study-specific activities.
3. Study population
Patients ≥18 years old and ≤ 80 years old with a primary diagnosis of AMI between January 1, 2010, and December 31, 2024 were eligible if they underwent cardiac catheterization during the index hospitalization and did not undergo percutaneous coronary intervention or coronary artery bypass grafting (Supplementary Tables 1 and 2). Because quantitative lesion severity and routine cardiac magnetic resonance imaging were not available in TriNetX, we operationalized the definition of MINOCA using structured EHR data to align with the 2019 AHA Scientific Statement definition of MINOCA [1].
We restricted the cohort to patients aged 18–80 years to reduce heterogeneity from pediatric and very elderly populations, where AMI etiologies, comorbidity burdens, and treatment approaches differ substantially and may not align with contemporary MINOCA management strategies.
To minimize misclassification, patients with alternative causes of elevated troponins unrelated to CAD were excluded using ICD-10 codes for heart failure exacerbation, Takotsubo syndrome, aortic or coronary dissection, acute myocarditis, pericarditis, infective endocarditis, acute hypertensive syndromes, cardiac arrest, major arrhythmias, pulmonary embolism, severe sepsis, major bleeding, end-stage renal disease, acute cerebrovascular accidents. Additionally, patients with poor short-term prognosis such as malignancy, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, which may have interfered with the decision of revascularization, were also excluded. Historical ICD-9 codes were mapped to ICD-10-CM using General Equivalence Mappings (GEMs) in combination with a proprietary algorithm and manual curation process developed by TriNetX during healthcare organization onboarding. This approach allowed harmonization of diagnostic data across coding eras and ensured consistent longitudinal analyses (Supplementary Table 3).
4. Exposure definition
The exposure of interest was colchicine use, defined as a documented prescription (RxNorm 2683) initiated on or after the index AMI hospitalization and continued for at least one year, regardless of indication. Data on colchicine dosage, adherence, and treatment duration beyond one year were not available in TriNetX.
5. Outcomes
The primary outcome was a composite of recurrent AMI, cerebrovascular accident or transient ischemic attack (CVA/TIA), all-cause hospitalizations, and all-cause mortality within five years of the index event. Secondary outcomes included the individual components of the composite. All outcomes were identified using standardized TriNetX query definitions (Supplementary Table 4) and were time-to-event variables measured from the date of the index AMI to discharge.
6. Statistical analysis
Continuous variables are presented as mean ± standard deviation (SD) and compared using independent-sample t-tests, while categorical variables are expressed as n (%) and analyzed via the chi-square test. To address baseline differences between the cohorts, extensive 1:1 propensity-score matching (PSM) was applied using a built-in algorithm that utilizes a greedy nearest-neighbor method with a caliper of 0.1 pooled SDs. PSM factors were selected based on the prior studies as well as the known confounders for CV outcomes. Extensive covariates used in the matching algorithm included demographics (age, sex, race), cardiovascular risk factors (hypertension, diabetes mellitus, hyperlipidemia, smoking status, chronic kidney disease), cardiovascular history (prior CAD, heart failure, atrial fibrillation), and inflammatory biomarkers (Table 1 and Supplementary Tables 5, and 6). Balance was assessed using standardized mean differences (SMD), with all covariates showing SMD <0.1 post-matching. All variables in Table 1 were analyzed based on the outcomes using the multivariable logistic regression model. Survival analysis was conducted by plotting Kaplan-Meier curves and comparing the two cohorts with log-rank tests. Statistical significance was defined by a two-sided P value of <0.05. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models. All statistical analyses were performed using the TriNetX online platform, with built-in R for statistical computing (Fig. 1).
Table 1.
Baseline characteristics of colchicine and control groups before and after propensity score matching.
| Before propensity score matching |
After propensity score matching |
||||
|---|---|---|---|---|---|
| Colchicine (n = 1221) |
Control (n = 42,167) |
Colchicine (n = 1188) |
Control (n = 1188) |
SMD | |
| Age, y | 54.5 ± 13.5 | 57.7 ± 11.1 | 54.5 ± 13.6 | 53.7 ± 13.3 | 0.060 |
| BMI, kg/m2 | 30.9 ± 7.1 | 30.4 ± 6.8 | 30.9 ± 7.2 | 31.2 ± 7.1 | 0.037 |
| White | 765 (62.7 %) | 29,548 (70.1 %) | 748 (63.0 %) | 752 (63.3 %) | 0.007 |
| Black | 205 (16.8 %) | 4957 (11.8 %) | 200 (16.8 %) | 207 (17.4 %) | 0.016 |
| Female | 263 (21.5 %) | 13,565 (32.2 %) | 260 (21.9 %) | 252 (21.2 %) | 0.016 |
| Medical conditions | |||||
| Diabetes mellitus | 317 (26.0 %) | 8583 (20.4 %) | 303 (25.5 %) | 307 (25.8 %) | 0.008 |
| Hypertension | 731 (59.9 %) | 18,429 (43.7 %) | 702 (59.1 %) | 707 (59.5 %) | 0.009 |
| Heart failure | 264 (21.6 %) | 4581 (10.9 %) | 245 (20.6 %) | 265 (22.3 %) | 0.041 |
| Atrial fibrillation | 226 (18.5 %) | 3020 (7.2 %) | 211 (17.8 %) | 212 (17.8 %) | 0.002 |
| Chronic kidney disease | 166 (13.6 %) | 2303 (5.5 %) | 153 (12.9 %) | 146 (12.3 %) | 0.018 |
| Chronic obstructive pulmonary disease | 76 (6.2 %) | 2426 (5.8 %) | 74 (6.2 %) | 87 (7.3 %) | 0.044 |
| Obstructive sleep apnea | 189 (15.5 %) | 2706 (6.4 %) | 182 (15.3 %) | 192 (16.2 %) | 0.023 |
| Atherosclerotic heart disease without Angina | 693 (56.8 %) | 15,089 (35.8 %) | 664 (55.9 %) | 662 (55.7 %) | 0.003 |
| Alcohol-related disorders | 74 (6.1 %) | 1417 (3.4 %) | 69 (5.8 %) | 69 (5.8 %) | <0.001 |
| Overweight and obesity | 335 (27.4 %) | 6692 (15.9 %) | 321 (27.0 %) | 340 (28.6 %) | 0.036 |
| Nicotine dependence | 150 (12.3 %) | 4283 (10.2 %) | 142 (12.0 %) | 154 (13.0 %) | 0.031 |
| Gout | 258 (21.1 %) | 640 (1.5 %) | 232 (19.5 %) | 197 (16.6 %) | 0.077 |
| Behçet's disease | 10 (0.8 %) | 10 (0 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Chronic constrictive pericarditis | 10 (0.8 %) | 10 (0 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Febrile neutrophilic dermatosis | 10 (0.8 %) | 11 (0 %) | 10 (0.8 %) | 0 (0 %) | 0.130 |
| Postcardiotomy syndrome | 10 (0.8 %) | 10 (0 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Chondrocalcinosis | 10 (0.8 %) | 36 (0.1 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Transient cerebral ischemic attacks | 19 (1.6 %) | 324 (0.8 %) | 19 (1.6 %) | 19 (1.6 %) | <0.001 |
| Systemic connective tissue disorders | 18 (1.5 %) | 352 (0.8 %) | 17 (1.4 %) | 18 (1.5 %) | 0.007 |
| Other rheumatoid arthritis | 25 (2.0 %) | 416 (1.0 %) | 24 (2.0 %) | 33 (2.8 %) | 0.050 |
| Inflammatory polyarthropathies | 309 (25.3 %) | 1645 (3.9 %) | 283 (23.8 %) | 263 (22.1 %) | 0.040 |
| Noninfective enteritis and colitis | 50 (4.1 %) | 931 (2.2 %) | 46 (3.9 %) | 36 (3.0 %) | 0.046 |
| Low socioeconomic status | 59 (4.8 %) | 820 (1.9 %) | 53 (4.5 %) | 58 (4.9 %) | 0.020 |
| Medications | |||||
| Aspirin | 889 (72.8 %) | 18,410 (43.7 %) | 859 (72.3 %) | 854 (71.9 %) | 0.009 |
| Atorvastatin | 673 (55.1 %) | 13,561 (32.2 %) | 647 (54.5 %) | 642 (54.0 %) | 0.008 |
| Rosuvastatin | 162 (13.3 %) | 3328 (7.9 %) | 157 (13.2 %) | 143 (12.0 %) | 0.035 |
| Simvastatin | 61 (5.0 %) | 2083 (4.9 %) | 61 (5.1 %) | 67 (5.6 %) | 0.022 |
| Beta blockers | 820 (67.2 %) | 16,842 (40.0 %) | 789 (66.4 %) | 788 (66.3 %) | 0.002 |
| Clopidogrel | 338 (27.7 %) | 6319 (15.0 %) | 321 (27.0 %) | 336 (28.3 %) | 0.028 |
| Ticagrelor | 185 (15.2 %) | 1816 (4.3 %) | 175 (14.7 %) | 182 (15.3 %) | 0.016 |
| Prasugrel | 52 (4.3 %) | 762 (1.8 %) | 50 (4.2 %) | 51 (4.3 %) | 0.004 |
| Warfarin | 43 (3.5 %) | 656 (1.6 %) | 42 (3.5 %) | 43 (3.6 %) | 0.005 |
| Apixaban | 112 (9.2 %) | 1069 (2.5 %) | 106 (8.9 %) | 111 (9.3 %) | 0.015 |
| Rivaroxaban | 45 (3.7 %) | 545 (1.3 %) | 42 (3.5 %) | 36 (3.0 %) | 0.028 |
| Dabigatran etexilate | 10 (0.8 %) | 68 (0.2 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Cilostazol | 10 (0.8 %) | 125 (0.3 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Methotrexate | 10 (0.8 %) | 169 (0.4 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Leflunomide | 10 (0.8 %) | 47 (0.1 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Hydroxychloroquine | 16 (1.3 %) | 207 (0.5 %) | 15 (1.3 %) | 12 (1.0 %) | 0.024 |
| Sulfasalazine | 10 (0.8 %) | 48 (0.1 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Azathioprine | 10 (0.8 %) | 44 (0.1 %) | 10 (0.8 %) | 10 (0.8 %) | <0.001 |
| Laboratory | |||||
| C-reactive protein, mg/L | 35.7 ± 55.7 | 27.1 ± 52.4 | 32.7 ± 51.5 | 29.4 ± 50.8 | 0.148 |
| Erythrocyte sedimentation rate, mm/h | 27.4 ± 26.3 | 23.3 ± 24.2 | 25.7 ± 24.4 | 24.1 ± 23.7 | 0.057 |
| Cholesterol in LDL, mg/dL | 92.4 ± 40.9 | 99.0 ± 41.7 | 92.4 ± 41.0 | 93.2 ± 40.8 | 0.058 |
| Cholesterol in HDL, mg/dL | 39.9 ± 16.4 | 42.5 ± 18.0 | 40.0 ± 16.5 | 41.0 ± 17.2 | 0.060 |
| Total cholesterol, mg/dL | 161.8 ± 48.8 | 170.5 ± 52.5 | 162.0 ± 49.0 | 163.5 ± 48.7 | 0.056 |
| Lipoprotein a, nmol/L | 110.0 ± 206.9 | 82.2 ± 83.8 | 110.0 ± 206.9 | 95.4 ± 102.5 | 0.449 |
Values are mean ± SD or n (%). To maintain patients' anonymity and confidentiality, the TriNetX database represents variables with occurrences of 10 or fewer than 10 as ≤10.
This table summarizes demographic variables, medical history, and medication use for colchicine-treated MINOCA patients and matched controls, both before and after propensity score matching. P-values indicate the statistical significance of group differences, with p ≤ 0.05 considered significant.
Fig. 1.
Flow diagram of cohort selection and propensity score matching.
Patients were identified using the TriNetX Research Network. Full ICD-10 and CPT codes are listed in the Supplementary Material.
7. Results
A total of 1188 patients who received colchicine and met inclusion criteria were propensity score matched 1:1 with 1188 control patients. After matching, baseline characteristics and medication use were well balanced (Table 1). Female representation was 21.9 % in the colchicine group and 21.2 % in the control group (p = 0.690). Other comorbidities and socioeconomic factors were evenly distributed (Table 1). Inflammatory markers including CRP (32.7 ± 51.5 mg/L vs. 29.4 ± 50.8 mg/L; p = 0.112) and erythrocyte sedimentation rate (25.7 ± 24.4 mm/h vs. 24.1 ± 23.7 mm/h; p = 0.557), were similarly elevated across groups where results were available (Table 1).
The primary composite outcome of AMI recurrence, all-cause mortality, cerebrovascular events, and hospitalizations was significantly lower in patients with MINOCA treated with colchicine compared with controls (49.0 % vs 55.1 %; HR 0.839; 95 % CI 0.750–0.938; p < 0.001). Among secondary outcomes, AMI recurrence (26.9 % vs 33.5 %; HR 0.749; 95 % CI 0.646–0.867; p < 0.001) and all-cause mortality (1.9 % vs 3.9 %; HR 0.518; 95 % CI 0.312–0.862; p < 0.001) were significantly lower in the colchicine arm. There was a clinical benefit in heart failure events (19.7 % vs 22.7 %; HR 0.861; 95 % CI 0.723–1.026; p > 0.05) and all-cause hospitalizations (33.8 % vs 37.5 %; HR 0.892; 95 % CI 0.779–1.020; p = 0.764) in patients on colchicine, however, this difference was not statistically significant. There was no difference in cerebrovascular events between the two groups (1.3 % vs 1.0 %; HR 1.364; 95 % CI 0.638–2.914; p = 0.820) (Fig. 2 and Fig. 3A-B).
Fig. 2.
Colchicine vs. control group outcomes in MINOCA.
A bar graph displaying the percentage of acute myocardial infarction recurrence, heart failure events, all-cause hospitalizations, all-cause mortality, and the composite outcome within five years of the index event for colchicine- and control-treated MINOCA patients. P-values are based on hazard ratios; p-values ≤ 0.05 indicate statistical significance.
Fig. 3.
Association of colchicine use with outcomes in MINOCA.
A. Forest plot of hazard ratios (HRs) with 95 % confidence intervals for the primary composite endpoint (recurrent acute myocardial infarction, heart failure, cerebrovascular accident/transient ischemic attack, all-cause hospitalization, and all-cause mortality) and each component in the propensity score–matched cohort; the vertical line marks HR = 1.0 (no difference), and HRs < 1.0 favor colchicine. B. Kaplan–Meier curves for all-cause mortality over five years comparing colchicine users with non-users; p value from the log-rank test is shown.
8. Discussion
In this first large real-world retrospective study of colchicine in patients with MINOCA, use of colchicine for at least one year after the index event was associated with a significantly lower risk of the primary composite outcome of AMI recurrence, all-cause mortality, cerebrovascular events, and hospitalizations. Among secondary outcomes, colchicine users had significantly lower rates of AMI recurrence and all-cause mortality. Heart failure events and all-cause hospitalizations were clinically lower in the colchicine group, although these differences did not reach statistical significance. Rates of cerebrovascular events were similar between groups. Although causality cannot be established, colchicine's anti-inflammatory properties likely contribute to this effect.
Inflammation plays a central role in the pathophysiology of atherosclerosis and acute coronary syndromes. Large randomized controlled trials have demonstrated that anti-inflammatory therapies significantly improve cardiovascular outcomes in these patients. Landmark trials such as Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) demonstrated that targeting interleukin-1β with canakinumab reduced recurrent cardiovascular events in patients with prior MI and elevated CRP [9]. Low-dose colchicine has emerged as an accessible anti-inflammatory therapy in CAD. The Colchicine Cardiovascular Outcomes Trial (COLCOT) showed that colchicine 0.5 mg daily reduced ischemic events after recent MI, while low-dose colchicine (LoDoCo2) trial demonstrated benefit in stable chronic CAD [10,11]. However, there are mixed results to support its use after MI which was seen in the CLEAR Synergy (OASIS 9) trial [7,12]. Inclusion of sicker patients presenting with STEMI who received colchicine within two days of the index event is postulated to have influenced the unfavorable outcomes in the CLEAR Synergy trial over the COLCOT trial [7,[12], [13], [14]].
The COLCOT trial included patients with STEMI and NSTEMI and had an average lead time of about 2 weeks prior to being included in the trial [14]. Both STEMI and NSTEMI are associated with a significant amount of myocardial injury, while MINOCA has more inflammatory damage over myocardial injury [15]. In our cohorts, the mean CRP and ESR levels were comparably elevated in both groups indicating systemic inflammation and supporting the observed benefits of colchicine's anti-inflammatory effect. In patients with stable CAD, the anti-inflammatory effects of colchicine have been attributed to improved cardiovascular outcomes, and we suspect our favorable results are also a result of this effect.
Colchicine inhibits tubulin-dependent activation of the NLRP3 inflammasome and downstream IL-1 and IL-6 signaling, while reducing neutrophil trafficking and NET formation. These actions dampen vascular inflammation, limit leukocyte–endothelial adhesion, and improve microvascular flow [3,15]. Inflammatory biomarkers along these pathways are elevated in MINOCA cohorts, supporting a pathophysiologic role for endothelial injury, coronary vasospasm, and microvascular obstruction in this population [2,15,16]. Overall, colchicine's anti-inflammatory and antithromboinflammatory effects provide a coherent biological rationale for the pattern of benefit seen in our cohort (Fig. 4). These results warrant confirmation in prospective, mechanism-specific clinical trials.
Fig. 4.
Proposed mechanism and clinical impact of colchicine in MINOCA.
A) Colchicine inhibits NLRP3 inflammasome activation, reducing IL-1β, IL-18, and IL-6 release, thereby mitigating endothelial dysfunction and microvascular injury, key contributors to MINOCA.
This figure was created in BioRender. Oro, P. (2025) https://BioRender.com/8fzenwb.
Although outcomes are generally better than for MI with obstructive CAD, patients with MINOCA still have higher cardiovascular morbidity and mortality than the general population [17,18]. Despite growing recognition, evidence-based, disease-specific therapies remain limited, highlighting a clear unmet need. Heterogeneous etiologies, including plaque disruption, coronary spasm, microvascular dysfunction, embolism, and inflammation, complicate both diagnosis and treatment. Current guidelines offer no disease-specific pharmacotherapy for MINOCA, and secondary prevention strategies are generally extrapolated from obstructive MI studies despite limited supporting evidence. Its relatively low event rate makes it difficult to pursue clinical trials and the absence of a specific diagnostic code for MINOCA complicates database research. The growing body of evidence linking inflammation to MINOCA provides a strong rationale for exploring colchicine as a potential therapeutic strategy [13].
To our knowledge, our study is the first large-scale, real-world analysis examining the association between colchicine use and long-term outcomes in patients meeting EHR-based criteria for MINOCA. By leveraging the TriNetX network, we evaluated a diverse, multi-institutional cohort over a 5-year follow-up period. These findings suggest that colchicine, a commonly available anti-inflammatory medication, may have potential benefits in this population lacking evidence-based therapeutic options.
9. Limitations
This study has several limitations. First, its retrospective design and reliance on ICD-10, CPT, and RXNORM codes introduce the potential for misclassification bias, as MINOCA is a heterogeneous condition with various underlying mechanisms. Without systematic chart review or additional imaging modalities such as cardiac magnetic resonance imaging, intravascular ultrasound, or optical coherence tomography, distinguishing MINOCA from other causes of myocardial injury remains challenging. Furthermore, due to the nature of the study, quantifying coronary obstruction was not feasible. However, given the relatively young patient population, it is assumed that these patients did not have significant coronary obstruction necessitating intervention. Additionally, MINOCA is often female-predominant [1,19]. However, females made up approximately 22 % of our total population, which is lower than typically expected in patients with MINOCA. This is possibly due to higher prevalence of nonobstructive CAD and gout in our cohort, both more common in men. Moreover, the absence of serial biomarker measurements for inflammation limits our ability to link colchicine's benefit to inflammation reduction. The exact duration of colchicine therapy was not available. However, the exposure definition reflects at least one year of documented use of colchicine on or after the index myocardial infarction. Residual confounding factors, such as medication adherence, lifestyle differences, healthcare utilization, or genetic predispositions, could also have influenced outcomes. Lastly, given its observational nature, the study cannot establish causality.
10. Conclusions
MINOCA is relatively common, yet there remains a paucity of evidence-based targeted therapy due to the heterogeneous nature of its pathophysiology. In our study, the use of colchicine in patients with MINOCA showed a trend toward improved cardiovascular outcomes. We hypothesize that these effects reflect colchicine's anti-inflammatory actions that may mitigate endothelial injury, vasospasm, and microvascular obstruction in this population. These findings are hypothesis-generating and need validation with prospective studies. However, our study suggests that in patients with MINOCA, where treatment options are limited, the use of colchicine may improve cardiovascular outcomes.
CRediT authorship contribution statement
Peter Oro: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Aravinthan Vignarajah: Writing – review & editing, Writing – original draft, Validation, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Joseph El Dahdah: Writing – review & editing, Methodology, Data curation, Conceptualization. Nishanthi Vigneswaramoorthy: Writing – review & editing, Conceptualization. Yousif Awakeem: Writing – review & editing. Gautam V. Shah: Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Data curation, Conceptualization.
Ethical approval
Data is deidentified, and Institutional Review Board approval is not required.
Ethical statement
This study was conducted using data from the TriNetX research platform, a global federated health research network that provides access to de-identified, aggregate-level electronic health records. All analyses were performed within the secure TriNetX platform environment, which does not allow for the download or viewing of individual-level patient data. The data used are de-identified in compliance with the Health Insurance Portability and Accountability Act (HIPAA).
Because the TriNetX platform provides only de-identified data and does not involve interaction with human subjects or access to protected health information, the use of this data qualifies for exemption from institutional review board (IRB) oversight. TriNetX operates under a waiver granted by a central IRB (Western IRB). Therefore, this study did not require separate IRB approval. The research was conducted in accordance with the principles of the Declaration of Helsinki and all applicable regulatory standards.
Funding
This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.ahjo.2025.100643.
Appendix A. Supplementary data
Supplementary tables
References
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