Multicenter Trial of Antithrombotic Strategies in Acute Coronary Syndrome With Coronary Artery Ectasia

Официальное название

Dual Antiplatelet Therapy Versus Antiplatelet Monotherapy Plus Anticoagulation in Patients With Acute Coronary Syndrome and Coronary Artery Ectasia: A Multicenter Randomized Clinical Trial

Обзор

Coronary artery ectasia (CAE) is a condition in which a coronary artery becomes abnormally dilated, measuring at least 50% larger than the adjacent normal segment. Although relatively uncommon, CAE is clinically important because it can lead to abnormal blood flow and increase the risk of blood clot formation. Patients with CAE are at higher risk of angina, myocardial infarction, and complications during coronary interventions. Despite these risks, the optimal antithrombotic treatment for patients with acute coronary syndrome (ACS) and CAE remains uncertain. Dual antiplatelet therapy (aspirin plus clopidogrel) is currently the most commonly used treatment. However, the abnormal blood flow patterns observed in CAE may promote clot formation through mechanisms that could potentially be better addressed with anticoagulant therapy. The OVER-TIME II trial is a multicenter randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and CAE: standard dual antiplatelet therapy versus antiplatelet monotherapy combined with anticoagulation. The study aims to determine whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.

Подробное описание

Coronary artery ectasia (CAE) is defined as an abnormal dilatation of a coronary artery segment measuring at least 50% greater than the diameter of the adjacent normal segment. Although relatively uncommon, CAE represents a clinically relevant phenotype of coronary artery disease. Its reported prevalence ranges from 0.3% to 4.9% worldwide; however, higher frequencies have been described in certain populations. At the National Institute of Cardiology "Ignacio Chávez" (INCICh) in Mexico, a prevalence of approximately 10.3% has been documented among patients presenting with ST-segment elevation myocardial infarction (STEMI), highlighting the importance of studying this condition in the Mexican population.

The pathophysiology of CAE involves abnormal coronary blood flow dynamics, including turbulent flow and blood stasis within dilated segments. These changes may promote thrombus formation through multiple mechanisms, including platelet activation, local inflammatory processes, endothelial dysfunction, and potential prothrombotic states. Genetic susceptibility and molecular pathways related to vascular remodeling may also contribute to the development and progression of the disease. Clinically, patients with CAE have been associated with a higher risk of angina, myocardial infarction, distal embolization, and complications during percutaneous coronary intervention.

Despite its clinical significance, the optimal antithrombotic strategy in patients with acute coronary syndrome (ACS) and CAE remains uncertain. Dual antiplatelet therapy (DAPT), typically consisting of aspirin and a P2Y12 inhibitor, is the most commonly used treatment. However, given the propensity for thrombus formation related to abnormal flow conditions in ectatic coronary segments, anticoagulation has been proposed as a potentially beneficial therapeutic strategy.

The exploratory OVERTIME trial conducted at INCICh compared an antithrombotic regimen consisting of antiplatelet monotherapy plus a direct oral anticoagulant (clopidogrel 75 mg plus rivaroxaban 15 mg daily) with standard dual antiplatelet therapy (aspirin 100 mg plus clopidogrel 75 mg daily) in patients with ACS and CAE. Although limited by sample size, the study demonstrated a numerical reduction in major adverse cardiovascular events and a shorter endogenous fibrinolysis time among patients receiving the combination of antiplatelet therapy and anticoagulation, without a significant increase in bleeding events.

These findings support the hypothesis that anticoagulation combined with antiplatelet therapy may improve clinical outcomes in this high-risk population. However, larger randomized studies are needed to confirm these results and provide definitive evidence to guide clinical management.

The OVER-TIME II trial is a multicenter, randomized clinical trial designed to compare two antithrombotic strategies in patients with ACS and angiographically confirmed CAE: (1) standard dual antiplatelet therapy and (2) antiplatelet monotherapy combined with oral anticoagulation. The primary objective is to evaluate whether the addition of anticoagulation reduces major cardiovascular events without significantly increasing bleeding risk.

In addition to the clinical trial component, the study will incorporate a translational research arm. Peripheral blood samples will be collected to investigate genetic variants and DNA and RNA expression profiles that may be associated with susceptibility to CAE, disease progression, and differential response to antithrombotic therapy. These analyses aim to improve the understanding of the biological mechanisms underlying CAE and to identify potential biomarkers that could inform future personalized treatment strategies.

Вмешательства

• Препарат Aspirin 100 mg
  Participants receive aspirin 100 mg once daily
• Препарат Clopidogrel 75 mg
  Participants receive clopidogrel 75 mg once daily
• Препарат Rivaroxaban 15 mg
  Participants receive oral anticoagulation using rivaroxaban 15 mg once daily

Первичные конечные точки

• Time to First Major Adverse Cardiovascular Event (MACE) [Срок оценки: 12 months]
• Time to First Bleeding Event According to the BARC Classification [Срок оценки: 12 months]

Вторичные конечные точки (2)

• Individual Components of the Major Adverse Cardiovascular Event Composite [Срок оценки: 12 months]
• Individual Bleeding Events According to the BARC Classification [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Adults aged 18 to 80 years, of either sex, hospitalized with acute coronary syndrome (ACS) with or without ST-segment elevation.
• Recent ACS within 7 days prior to enrollment, defined by all of the following:
• Clinical presentation consistent with acute coronary syndrome.
• Elevated high-sensitivity cardiac troponin above the 99th percentile.
• Presence or absence of persistent ST-segment elevation.
• Coronary artery ectasia in the culprit coronary artery, defined by all of the following:
• The presence of ectasia will be determined by agreement of two expert interventional cardiologists, and will be confirmed by quantitative coronary angiography (QCA).
• Identification of a culprit artery consistent with the electrocardiographic territory involved (in cases with ST-segment elevation) or with angiographic features suggestive of an atherothrombotic event, such as the presence of thrombus or reduced coronary flow.
• Hospital admission lasting more than 24 hours.
• Management with either percutaneous coronary intervention or medical therapy, as determined by the treating medical team. Intracoronary interventions such as stent implantation, balloon angioplasty, or thrombus aspiration are permitted.
• Ability and willingness to provide written informed consent and to participate in the study.

Критерии исключения

• Pregnant women.
• Current indication for temporary or long-term anticoagulation therapy at the time of enrollment.
• Severe chronic kidney disease, defined as KDIGO stage G4 or higher (estimated glomerular filtration rate \[eGFR\] <30 mL/min/1.73 m²).
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² at hospital discharge.
• History of major bleeding, active bleeding, or high bleeding risk, including but not limited to gastrointestinal bleeding, intracranial hemorrhage, or other conditions considered by the treating physician to confer a high risk of bleeding.
• Advanced heart failure, defined as left ventricular ejection fraction (LVEF) <30% plus at least one of the following:
• More than two hospitalizations or unplanned emergency department visits for heart failure in the past year, or
• NYHA functional class III or IV symptoms despite optimal medical therapy at enrollment or within the previous 3 months.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Мексика · 1 центр

• Instituto Nacional de Cardiologia "Ignacio Chávez" — Mexico City

Публикации

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• Araiza-Garaygordobil D, Gopar-Nieto R, Sierra-Lara Martinez JD, Mullasari AS, Belderrain-Morales N, Najera-Rojas NA, Diaz-Herrera BA, Sarabia-Chao V, Alfaro-Ponce DL, Briseno-De la Cruz JL, Ruiz-Beltran M, Martinez-Rios MA, Pina-Reyna Y, Latapi-Ruiz Esparza X, Grimaldo-Gomez FA, Cortina-De la Rosa E, Romero-Arroyo MO, Sierra-Gonzalez de Cossio A, Gonzalez-Pacheco H, Arias-Mendoza A. A randomized t PMID 39615618
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• Nunez-Gil IJ, Cerrato E, Bollati M, Nombela-Franco L, Terol B, Alfonso-Rodriguez E, Camacho Freire SJ, Villablanca PA, Amat Santos IJ, de la Torre Hernandez JM, Pascual I, Liebetrau C, Camacho B, Pavani M, Albistur J, Latini RA, Varbella F, Jimenez-Diaz VA, Piraino D, Mancone M, Alfonso F, Linares JA, Rodriguez-Olivares R, Jimenez Mazuecos JM, Palazuelos Molinero J, Sanchez-Grande Flecha A, Gomez- PMID 31378382
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Идентификаторы

NCT: NCT07511257 · 26-1556

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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