In this real-world observational study, we did not find evidence to support the use of anticoagulants in addition to antiplatelets in patients with CAE after an ACS. Our series represents the largest dataset to date comparing DAPT versus anticoagulation in this population with such prolonged follow-up. In our cohort, neither composite MACE, its individual components, nor composite bleeding events showed a statistically significant difference between both groups. These results persisted after propensity score matching analysis.

Our results contrast with those previously published. Doi et al. studied outcomes in 8 patients after acute MI with CAE taking warfarin whose TTR was above 60% compared with 43 patients whose TTR was below 60% or who were not taking warfarin [17]. Patients taking warfarin presented a statistically significant lower prevalence of reinfarction and cardiovascular death. However, a group taking DAPT was not analyzed in Doi’s study. Pranata et al. analyzed a series of cases of patients taking anticoagulation therapy versus single antiplatelet therapy (SAPT) or DAPT. Thirteen cases were studied where those taking optimal anticoagulation had a lower recurrence rate, with a mean follow-up of 8.4 months. Only 2 out of the 13 were taking DOACs [18]. Another 3 cases were described by Yan et al. where patients taking a DOAC had no ACS recurrence or any other MACE with a maximum follow-up of 12 months [23]. Our study had a median follow-up of about 32 months, contrasting with the studies previously mentioned. Additionally, Amirpour et al. (2024) published a systematic review including 457 patients, incorporating the studies mentioned above, which compared antiplatelet and anticoagulant regimens in relation to major adverse cardiovascular events (MACE). They concluded that combining antiplatelet therapy with anticoagulants may reduce MACE recurrence [24]. However, it must be pointed out that most of the included studies were case reports, some with short follow-up periods. Only one randomized controlled trial was identified, but at the time, it had only published its rationale, and its outcomes were not included. This RCT, published by Araiza-Garaygordobil (2024), has since reported results, observing no statistical difference in MACE between patients treated with DAPT (aspirin 100 mg daily plus clopidogrel 75 mg daily) and those treated with SAPT + OAC (Rivaroxaban 15 mg daily plus clopidogrel 75 mg daily) [25]. More recently, Azarboo et al. (2025) conducted a systematic review and network meta-analysis that included 1,106 patients divided into four treatment groups: dual antiplatelet therapy (DAPT), anticoagulants, aspirin alone, and no treatment. Their findings demonstrated that DAPT was the most effective strategy for preventing MACE in patients with coronary artery ectasia (CAE), followed by aspirin alone, anticoagulants, and no treatment. These results not only align with our findings—supporting the non-superiority of anticoagulants over DAPT—but also suggest that DAPT may lead to improved clinical outcomes and fewer adverse events [26].

Importantly, anticoagulant treatment has evolved substantially in the last few decades, with DOACs emerging as valuable and effective therapies [27]. In this particular clinical scenario, DOAC effectiveness in ACS has only been reported as clinical cases, lacking sufficient evidence to either rule in or rule out its use as treatment. In our study, DOAC effectiveness was analyzed along with VKAs as a whole entity.

A second finding in our population was a higher incidence of GUSTO mild bleeding events with anticoagulation therapy, while antiplatelet therapy was associated with higher GUSTO moderate bleeding events. The latter might be explained by a higher percentage of patients in the DAPT group with a HAS-BLED score ≥ 2. However, composite bleeding events and net adverse clinical events did not differ among groups. Our findings suggest that both groups of patients have similar outcomes. Still, patients treated with anticoagulants may have an increased risk of mild bleeding, and the relatively small sample size may obscure the risk of major bleeding. In patients after ACS without CAE, DOAC users have been found to have a lower recurrence of MACE at the expense of increasing major bleeding in a dose-dependent manner [28, 29].

A third key finding in our study was the difference in clinical presentation and treatment between groups. In our population, the anticoagulants ± antiplatelets group presented more frequently with STEMI. They were also less likely to have been treated with a stent and more likely to have been treated with thromboaspiration and/or a GpIIa/IIIb inhibitor, probably due to the severity of the ectasia. The prevalence of TIMI scores after intervention and TMP scores above 2 was higher in the DAPT group. A likely explanation is the variation in clinical presentation, severity of ectasia, and treatment among groups. Treatment strategies may influence determining if anticoagulation has a role in MACE prevention, as patients who have undergone thromboaspiration rather than stenting may have a stronger indication for anticoagulation. Further studies on additional factors and how they influence treatment indications must be conducted, including stenting, number of stents used, thromboaspiration, and GpIIa/IIIb inhibitor use.

Moreover, CAE encompasses several subgroups of patients with distinct characteristics, including varying numbers of affected arteries and the extent of involvement in each artery. The anticoagulants ± antiplatelets group had lower Markis scores in our population, indicating more diffuse disease. In our multivariate analysis, diffuse presentations of all three arteries were associated with the primary outcome. A previous study by Gunasekaran et al. categorized Markis 1 and 2 as high-grade ectasia and Markis 3 and 4 as low-grade ectasia [16]. High-grade disease had a significantly higher rate of ACS, and antithrombotic therapy was associated with a lower rate [16]. Additionally, certain ectasia locations may be associated with a higher risk of MACE and may warrant anticoagulation therapy; as in our multivariate analysis, LAD location was significantly associated with the main outcome. All the factors previously stated in this paragraph lead us to question if we should define the use of anticoagulation depending not only on the Markis classification but also on the severity and location of the ectasia itself.

Our findings should be interpreted considering certain limitations. A first limitation was that, to broaden our study population, the DAPT group and the anticoagulants ± antiplatelets group included different treatment combinations and different doses of anticoagulants. No specific drug combination was studied. We propose further analysis with treatment subgroups or standardized treatment.

Our study lacked randomization in grouping due to its nature, so the baseline characteristics differed. In addition to those previously mentioned, the DAPT group was more likely to receive a stent, while the anticoagulants ± antiplatelets group had greater use of GpIIb/IIIa inhibitors. This suggests the possibility of different causal mechanisms in each group, with a predominance of classic atheromatous disease in the DAPT group and in situ thrombus formation in the anticoagulants ± antiplatelets group. On the other hand, although both groups have coronary ectasia, it’s possible that some patients didn’t receive a stent due to a more severe disease phenotype characterized by larger arterial diameters. On several occasions, this hindered stent placement and limited treatment to thrombectomy and GpIIb/IIIa inhibitors. Even with propensity score matching to address this, the evidence remains less definitive than that from an RCT.

It’s essential to consider these limitations since, while the clinical outcomes were not significant, having a different causal mechanism for acute coronary syndrome or different spectra of the same disease may influence patient prognosis, regardless of the treatment received. The evidence remains controversial; traditionally, the Markis classification associates worse prognosis with increased vessel involvement. However, recent studies suggest that vessel size does not impact MACE occurrence [30].

Despite the limitations previously mentioned, this study lays a foundation for better determining a gold standard treatment for CAE. Our analysis suggests that DAPT therapy may have the same effectiveness as anticoagulation in this population. If this is true, other factors support DAPT, as it carries a lower financial burden than DOACs. Additionally, antiplatelet therapy has fewer interactions than VKAs, and there’s no need to measure INR to ensure patients stay within the therapeutic range.

Currently, more randomized controlled trials are comparing standard DAPT versus anticoagulation in CAE patients with a primary endpoint of MACE [31, 32]. We await results to guide therapy for CAE.