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Page 6 of 14 Barioli et al. Vessel Plus 2024;8:13 https://dx.doi.org/10.20517/2574-1209.2023.68

Regarding vasodilator administration, Kruger et al. demonstrated that nitroglycerin worsened myocardial
ischemia and its effect was related to coronary artery diameters. Taken these data into account, nitrates are
[19]
not recommended in case of significant aneurysmal coronary disease .

In patients with acute coronary syndromes or stable CAD undergoing PCI and stenting, antithrombotic
management should follow the treatment guidelines for ischemic heart disease [35-37] . In the absence of clear
indications for dual antiplatelet therapy (DAPT), there is no data from randomized clinical trials or large
prospective cohort studies supporting anticoagulation or DAPT in patients with CAA; moreover, the
available evidence from retrospective studies is discordant.

One study investigating the outcome of STEMI patients according to the presence of CAE showed an
increased risk of major adverse cardiac events (MACE) in the CAE group. Interestingly, CAE patients on
Warfarin achieving a percent time in target therapeutic range (%TTR) ≥ 60% experienced significantly less
[38]
MACE, with respect to those not taking anticoagulant or with a %TTR < 60% (0% vs. 33%; P = 0.03) .

A recent Propensity Score Matching analysis, including patients from the Coronary Artery Aneurysm
Registry (CAAR), compared the incidence of primary coronary ischemic endpoint (composite of
myocardial infarction, unstable angina and aneurysm thrombosis) and bleeding in patients discharged with
or without anticoagulant (AC). After a 3-year median follow-up, the AC group showed a significantly lower
incidence of the primary endpoint (8.7% vs. 17.2%, respectively; P = 0.01), driven by a significant reduction
in unstable angina and aneurysm thrombosis, at the expense of a negligible higher risk of bleeding (mainly
[39]
BARC type 1) (P = 0.08) . However, nowadays, the only definite indication for anticoagulation in the
setting of CAA refers to selected Kawasaki patients with large aneurysms or those with rapidly expanding
ones .
[13]

Given the persistent uncertainties about the optimal antithrombotic strategy in the setting of CAA, the
OVER-TIME Phase 2 trial (ClinicalTrials.gov Identifier: NCT05233124) has been designed to compare
DAPT with aspirin plus a P2Y12 inhibitor versus Rivaroxaban 15 mg plus P2Y12 inhibitor for prevention of
recurrent ischemic events in patients with CAE and acute coronary syndromes . This study will be the first
[40]
randomized controlled trial to yield safety and efficacy data regarding two different antithrombotic
strategies in patients with CAE after acute coronary events.

Another clinical trial (ClinicalTrials.gov Identifier: NCT05718531) will evaluate different treatment
strategies (DAPT with aspirin 75 mg and clopidogrel 75 mg, dual therapy with rivaroxaban 2.5 mg BID and
aspirin 75 mg or clopidogrel 75 mg, triple therapy with rivaroxaban 2.5 mg BID, aspirin 75 mg and
clopidogrel 75 mg) in acute and chronic coronary syndrome patients diagnosed with coronary artery ectasia
either associated or not with obstructive CAD . This study is not yet recruiting.
[41]

Percutaneous interventions
Percutaneous coronary intervention for the treatment of CAA and CAE presents significant technical
challenges, and standardization of treatment is demanding due to the lack of dedicated devices. Optimal
stent sizing is mandatory to avoid stent malapposition and embolization . However, as already pointed
[42]
out, coronary angiography has some limitations when it comes to assessing coronary aneurysms, especially
in the case of endoluminal thrombosis, and may result in an underestimation of the true vascular lumen and
consequently stent undersizing. In these cases, pre-procedural IVUS assessment is highly recommended. In
patients presenting with acute myocardial infarction (MI), percutaneous treatment of an aneurysmal culprit
lesion is associated with lower procedural success and higher rates of adverse events, including death, MI