The Role of Anticoagulation in Acute Coronary Syndrome Patients with Coronary Artery Ectasia

Introduction

Coronary artery ectasia (CAE) is defined as an abnormal dilatation – either diffuse or segmental – of a portion of a coronary artery to a diameter 1.5 times greater than that of an adjacent normal segment.¹ Although CAE is considered rare, with a reported prevalence ranging from 0.85% to 5.3%,² it has gained increasing clinical attention because of its association with adverse cardiovascular outcomes.

One of the most critical concerns arises when CAE coexists with acute coronary syndrome (ACS) – a group of conditions associated with sudden, reduced blood flow to the heart. CAE in the context of ACS may complicate the clinical course, as the abnormal vessel anatomy can reduce coronary blood flow and promote thrombus formation, even when standard ACS treatments are applied.^3,4

Evidence suggests that patients with both CAE and ACS may experience worse outcomes than those with ACS alone. In such patients, impaired flow dynamics within ectatic arteries may increase the likelihood of thrombosis. While anticoagulants have been hypothesized to reduce adverse events in this setting, no randomized clinical trials have confirmed this approach.⁴

Currently, the treatment options for managing ACS in CAE patients vary, and include dual antiplatelet therapy (DAPT), DAPT combined with anticoagulants, and single antiplatelet therapy (SAPT) with anticoagulants. The emergence of non-vitamin K antagonist oral anticoagulants (NOACs) has further complicated decision-making, raising questions about whether to use NOACs or traditional warfarin in this context.

This review aims to analyze the current treatment strategies for ACS in patients with CAE, highlight the gaps in evidence, and propose considerations for future research and clinical practice.

Methods

The papers to be included in this systematic review and meta-analysis were sought in MEDLINE and Embase up to August 31, 2022. The search strategy was conducted using the following terms: “coronary artery ectasia” and “acute coronary syndrome”. Studies were screened by the title, abstract, and full text, by two independent investigators, based on the PRISMA 2020 checklist. The PRISMA flowchart is shown in Figure 1.

Figure 1 Study flow diagram.

Selection Criteria

The inclusion criteria for this review were all studies that reported a patient with CAE who presented with ACS. The exclusion criteria included not being able to retrieve the full text, patients not receiving coronary angiography, age <18 years, and no mention of treatment.

Results

Patient Characteristics

In total, 31 patients were identified who presented with CAE and ACS. Four of them had another episode of ACS during follow-up. Thus, there were 35 cases compatible with ACS and CAE. Ten of them were female. The average age of the patients was 55 years old. In most cases, the infarct-related artery (IRA) was the same artery as the one with aneurysm formation.

The Patient Profiles are Separated According to Different Treatments in Tables 1–3

Most of the patients received standard DAPT (n=13), while some of them received DAPT with anticoagulant (n=9). Six of the patients receiving only DAPT had ACS during follow-up. No ACS was reported in those taking DAPT or SAPT with an anticoagulant. Those taking only warfarin more often had myocardial infarction (MI) during follow-up. Three patients received a covered stent, none of whom had recurrent ACS during follow-up. Those who received a covered stent showed immediate resolution of the coronary aneurysm under angiography, and none of them had another episode of ACS after that; however these three patients received different combinations of treatment (warfarin alone, DAPT, or DAPT plus warfarin)

Table 1 Patients Receiving DAPT

Table 2 Patients Receiving DAPT and Anticoagulant Therapy

Table 3 Patients Receiving Single Anticoagulant Therapy or SAPT with Anticoagulant Therapy

Discussion

Coronary Artery Ectasia

CAE is a well-recognized angiographic finding, characterized by abnormal dilatation of the coronary arteries.²⁸ Although the specific mechanism leading to CAE is still unknown, the risk factors and pathophysiology behind CAD are also associated with CAE.²⁹ These risk factors include hypertension, hyperlipidemia, smoking cigarettes, and male gender. Atherosclerosis is the most well-known cause of CAE. Congenital and collagen vascular disorders, infections, iatrogenic disease, and cardiac lymphomas, among others, are also causes.² The hypothesis that CAE develops from CAD is supported by its frequent coexistence with CAD, and the observation of common histopathological findings, such as lipid deposition and hyalinization, destruction and reduction of the medial elastic fibers, and disruption of the internal and external elastic lamina.^30–32 Research has revealed that patients with CAE may have a higher incidence of ACS, as Takahito Doi et al reported that patients with CAE have an increased risk of major adverse cardiovascular events (MACE), cardiac death, or non-fatal MI.³³ However, Doi’s findings were based on a small, retrospective cohort with limited ethnic diversity, which may affect generalizability.³³ The real prevalence of ACS in patients with CAE needs further investigation.

Coronary Artery Ectasia and Acute Coronary Syndrome

When ACS is encountered in this group, the standard treatment is still unknown owing to the clinical observation that a significant number of patients present with recurrent ACS after DAPT. An antiplatelet agent (or agents) combined with an anticoagulant seems more effective in this group. Doi et al reported that 43/51 patients receiving warfarin reaching a time in therapeutic range (TTR) >60% did not have MACE, cardiac death, or non-fatal MI.³³ Pranata et al reported that the addition of an anticoagulant seemed to be more effective than DAPT alone, especially in isolated CAE without other obvious stenotic lesions.⁴ In our analysis, patients receiving a single anticoagulant had more recurrent ACS (1/2). Patients receiving DAPT also had a high rate of recurrence of MI (6/13). Those receiving DAPT with an anticoagulant, then transferring to a single antiplatelet agent after 1–3 months with an anticoagulant, had no recurrent MI (0/9). This is compatible with the previous observation. DAPT with an anticoagulant regimen is similar to the treatment for patients who had ACS with atrial fibrillation (AF). The IRA is most often the same artery as the one with aneurysm formation, which may explain why standard DAPT is associated with more complications, owing to the different mechanisms leading to ACS in the normal coronary artery and coronary ectasia. Abnormal vessel dilatation causing disturbed coronary flow is different from plaque rupture-induced ACS. The limited coronary artery flow, as in the case of the patient with AF, would increase the probability of thrombus formation in the coronary artery. This may explain the benefit of anticoagulants in this condition.

Covered Stents

Polytetrafluoroethylene (PTFE)-covered, balloon-expandable stents have been shown to be effective devices for percutaneous management and prevention of coronary aneurysms.³⁴ In our analysis, three patients received a covered stent, and no adverse events were reported, whether they received anticoagulants or not. This may provide an alternative treatment option for these patients.

Side Effects of Anticoagulation

In our analysis, some case reports did not mention the adverse effects of anticoagulants, such as anemia, gastrointestinal bleeding, or other bleeding events. Current guidelines for ACS suggest a duration of 1 week to 1 month for the combination of DAPT with NOAC in patients with high ischemic risk and low risk of bleeding events.^35,36 In our analysis, in patients receiving anticoagulants with DAPT, the anticoagulant would be taken off after 1–3 months of therapy. Our study did not assess the outcome of bleeding events. According to the APPRAISE-2 and ATLAS ACS 2-TIMI 51 trials, the rate of intracranial bleeding events in patients receiving NOAC combined with DAPT ranged from 0.2% to 0.7%. It may be safe to use DAPT with an anticoagulant for 1 month in CAE with ACS.

Limitations

There are some limitations to our analysis. First, there has been no long-term follow-up in these patients. The longest follow-up was 4 years, in one patient who received a covered stent. Other studies had follow-up durations between 1 and 18 months. Thus, some adverse ischemic events may have been neglected. Second, there were no adverse events regarding bleeding episodes, which is another issue with the combination of antiplatelets and anticoagulants. Third, some risk factors, such as smoking, diabetes mellitus, or hyperlipidemia, could not be analyzed. This may be another confounder in this analysis.

Further randomized controlled trials (RCTs) are essential to evaluate the benefits and side effects of anticoagulants in this group.

Conclusion

Most of the patients with CAE were diagnosed as a result of the clinical presentation of ACS. One retrograde observational study revealed that the most frequent clinical indication for catheterization was ACS, followed by stable angina pectoris and a positive stress test. Observational data suggest that the majority of CAE patients are concurrently diagnosed with CAD. This means that concurrent CAE with CAD is an important issue to consider. No clinical trials have evaluated the treatment in this group. However, based on current case series and analysis, administering an anticoagulant with an antiplatelet agent seemed to result in fewer ischemic events and was not associated with more bleeding events. Otherwise, in suitable cases, such as short lesions or non-branch CAE, a covered stent may be another option to manage CAE with ACS. Given the complexity and rarity of CAE with ACS, individualized treatment remains essential. This review emphasizes the critical need for further RCTs to improve outcomes in this understudied population.