GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Many medical conditions, including hypertension, diabetes, obesity, sleep apnea, and heart failure (HF), increase the risk for AF. Cardiomyocytes have unique metabolic characteristics to maintain adenosine triphosphate production. Significant changes occur in myocardial metabolism in AF. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been used to control blood glucose fluctuations and weight in the treatment of type 2 diabetes mellitus (T2DM) and obesity. GLP-1RAs have also been shown to reduce oxidative stress, inflammation, autonomic nervous system modulation, and mitochondrial function. This article reviews the changes in metabolic characteristics in cardiomyocytes in AF. Although the clinical trial outcomes are unsatisfactory, the findings demonstrate that GLP-1 RAs can improve myocardial metabolism in the presence of various risk factors, lowering the incidence of AF.

Advancing Guideline-Directed Medical Therapy in Heart Failure: Overcoming Challenges and Maximizing Benefits.

The delayed titration of guideline-directed drug therapy (GDMT) is a complex event influenced by multiple factors that often result in poor prognosis for patients with heart failure (HF). Individualized adjustments in GDMT titration may be necessary based on patient characteristics, and every clinician is responsible for promptly initiating GDMT and titrating it appropriately within the patient's tolerance range. This review examines the current challenges in GDMT implementation and scrutinizes titration considerations within distinct subsets of HF patients, with the overarching goal of enhancing the adoption and effectiveness of GDMT. The authors also underscore the significance of establishing a novel management strategy that integrates cardiologists, nurse practitioners, pharmacists, and patients as a unified team that can contribute to the improved promotion and implementation of GDMT.

Pulsed field ablation: A promising approach for ventricular tachycardia ablation.

Radiofrequency ablation (RFA) has been a central therapeutic strategy for ventricular tachycardia (VT). However, concerns about its long-term effectiveness and complications have arisen. Pulsed field ablation (PFA), characterized by its nonthermal, highly tissue-selective ablation technique, has emerged as a promising alternative. This comprehensive review delves into the potential advantages and opportunities presented by PFA in the realm of VT, drawing insights from both animal experimentation and clinical case studies. PFA shows promise in generating superior lesions within scarred myocardial tissue, and its inherent repetition dependency holds the potential to enhance therapeutic outcomes. Clinical cases underscore the promise of PFA for VT ablation. Despite its promising applications, challenges such as catheter maneuverability and proarrhythmic effects require further investigation. Large-scale, long-term studies are essential to establish the suitability of PFA for VT treatment.

Overcoming barriers for left atrial appendage thrombus: a systematic review of left atrial appendage closure.

BACKGROUND: Approximately 90% of intracardial thrombi originate from the left atrial appendage in non-valvular atrial fibrillation patients. Even with anticoagulant therapy, left atrial appendage thrombus (LAAT) still occurs in 8% of patients. While left atrial appendage closure (LAAC) could be a promising alternative, the current consensus considers LAAT a contraindication to LAAC. However, the feasibility and safety of LAAC in patients with LAAT have yet to be determined. METHODS: This systematic review synthesizes published data to explore the feasibility and safety of LAAC for patients with LAAT. RESULTS: This study included a total of 136 patients with LAATs who underwent successful LAAC. The Amulet Amplatzer device was the most frequently utilized device (48.5%). Among these patients, 77 (56.6%) had absolute contraindications to anticoagulation therapy. Cerebral protection devices were utilized by 47 patients (34.6%). Transesophageal echocardiography (TEE) is the primary imaging technique used during the procedure. Warfarin and novel oral anticoagulants were the main anticoagulant medications used prior to the procedure, while dual antiplatelet therapy was primarily used post-procedure. During a mean follow-up period of 13.2 ± 11.5 months, there was 1 case of fatality, 1 case of stroke, 3 major bleeding events, 3 instances of device-related thrombus, and 8 cases of peri-device leakage. CONCLUSIONS: This review highlights the preliminary effectiveness and safety of the LAAC procedure in patients with persistent LAAT. Future large-scale RCTs with varied LAAT characteristics and LAAC device types are essential for evidence-based decision-making in clinical practice.

Subarachnoid haemorrhage-induced reversible cardiac dysfunction: time course and potential mechanisms.

AIMS: Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. METHODS AND RESULTS: In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague-Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post-SAH. We determined neuropeptide Y (NPY) 1-5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. CONCLUSIONS: SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY-NPY1 receptor pathway, otherwise known as catecholamines.

Device therapy for patients with atrial fibrillation and heart failure with preserved ejection fraction.

Device therapy is a nonpharmacological approach that presents a crucial advancement for managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). This review investigated the impact of device-based interventions and emphasized their potential for optimizing treatment for this complex patient demographic. Cardiac resynchronization therapy, augmented by atrioventricular node ablation with His-bundle pacing or left bundle-branch pacing, is effective for enhancing cardiac function and establishing atrioventricular synchrony. Cardiac contractility modulation and vagus nerve stimulation represent novel strategies for increasing myocardial contractility and adjusting the autonomic balance. Left ventricular expanders have demonstrated short-term benefits in HFpEF patients but require more investigation for long-term effectiveness and safety, especially in patients with AF. Research gaps regarding complications arising from left ventricular expander implantation need to be addressed. Device-based therapies for heart valve diseases, such as transcatheter aortic valve replacement and transcatheter edge-to-edge repair, show promise for patients with AF and HFpEF, particularly those with mitral or tricuspid regurgitation. Clinical evaluations show that these device therapies lessen AF occurrence, improve exercise tolerance, and boost left ventricular diastolic function. However, additional studies are required to perfect patient selection criteria and ascertain the long-term effectiveness and safety of these interventions. Our review underscores the significant potential of device therapy for improving the outcomes and quality of life for patients with AF and HFpEF.

Enhancing myocardial function with cardiac contractility modulation: potential and challenges.

Cardiac contractility modulation (CCM) offers a novel therapeutic avenue for heart failure patients, particularly those unresponsive to cardiac resynchronization therapy within specific QRS duration ranges. This review elucidates CCM's mechanistic underpinnings, its impact on myocardial function, and utility across patient demographics. However, CCM is limited by insufficient data on mortality and hospitalization rate reductions, as well as the need for specialized device implantation skills. While prevailing research has concentrated on left ventricular effects, a knowledge gap persists for other patient subsets. Future inquiries should address combinatory treatment strategies, extended usage and the impact of atrial fibrillation on device implantation. Such expanded studies could refine therapeutic outcomes and widen the scope of beneficiaries.

The effectiveness and safety of temporary transvenous cardiac pacing leads placement into coronary sinus vein in patients with sick sinus syndrome.

BACKGROUND: The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. OBJECTIVE: We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). METHODS: We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X-ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first-attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. RESULTS: Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first-attempt success rate of lead placement was obviously increased in CSV group (both p < .05). Compared with that in RV group, the rate of leads displacement is lower in CSV group (both p < .05). There were three patients occurred cardiac perforation in RV group, but no cardiac perforation was reported in CSV group (p > .05). CONCLUSION: TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.

Advances in diagnosis and treatment of mechanical hemolysis following percutaneous interventional for valvular heart diseases. / å¿ƒè„ç“£è†œç— ä»‹å ¥æ²»ç–—æœ¯åŽæœºæ¢°æ€§æº¶è¡€è¯Šç–—è¿›å±•.

Valvular heart disease is one of the common heart diseases in clinical practice, characterized by valve stenosis and/or incomplete closure. At present, drug therapy, surgery, and emerging percutaneous intervention therapy are the main treating methods for heart valve disease. Although the research and development of percutaneous intervention therapy devices is relatively mature, there are still problems such as postoperative mechanical hemolysis. The occurrence of mechanical hemolysis is associated with factors such as excessive shear stress experienced by red blood cells, direct interaction between red blood cells and the heart and valve surfaces, and thrombus formation. Furthermore, the presence of postoperative infection and other hemolytic diseases can also affect the occurrence of mechanical hemolysis. Although most patients are asymptomatic when hemolysis occurs, there are still critical cases. This type of hemolysis can accelerate the deterioration of the condition, and even endanger life in severe cases. Therefore, elucidating the background, pathogenesis, epidemiology, and related clinical research progress of mechanical hemolysis after percutaneous intervention therapy for valvular heart disease is of great significance for guiding the standardized diagnosis and treatment of the disease.

Protective effects of catalpol on cardio-cerebrovascular diseases: A comprehensive review.

Catalpol, an iridoid glucoside isolated from Rehmannia glutinosa, has gained attention due to its potential use in treating cardio-cerebrovascular diseases (CVDs). This extensive review delves into recent studies on catalpol's protective properties in relation to various CVDs, such as atherosclerosis, myocardial ischemia, infarction, cardiac hypertrophy, and heart failure. The review also explores the compound's anti-oxidant, anti-inflammatory, and anti-apoptotic characteristics, emphasizing the role of vital signaling pathways, including PGC-1α/TERT, PI3K/Akt, AMPK, Nrf2/HO-1, estrogen receptor (ER), Nox4/NF-κB, and GRP78/PERK. The article discusses emerging findings on catalpol's ability to alleviate diabetic cardiovascular complications, thrombosis, and other cardiovascular-related conditions. Although clinical studies specifically addressing catalpol's impact on CVDs are scarce, the compound's established safety and well-tolerated nature suggest that it could be a valuable treatment alternative for CVD patients. Further investigation into catalpol and related iridoid derivatives may unveil new opportunities for devising natural and efficacious CVD therapies.

The GPIHBP1-LPL complex and its role in plasma triglyceride metabolism: Insights into chylomicronemia.

GPIHBP1 is a protein found in the endothelial cells of capillaries that is anchored by glycosylphosphatidylinositol and binds to high-density lipoproteins. GPIHBP1 attaches to lipoprotein lipase (LPL), subsequently carrying the enzyme and anchoring it to the capillary lumen. Enabling lipid metabolism is essential for the marginalization of lipoproteins alongside capillaries. Studies underscore the significance of GPIHBP1 in transporting, stabilizing, and aiding in the marginalization of LPL. The intricate interplay between GPIHBP1 and LPL has provided novel insights into chylomicronemia in recent years. Mutations hindering the formation or reducing the efficiency of the GPIHBP1-LPL complex are central to the onset of chylomicronemia. This review delves into the structural nuances of the GPIHBP1-LPL interaction, the consequences of mutations in the complex leading to chylomicronemia, and cutting-edge advancements in chylomicronemia treatment.

Changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease: proteomics in human left atrial appendage tissue.

Background: Correlations between posttranslational modifications and atrial fibrillation (AF) have been demonstrated in recent studies. However, it is still unclear whether and how ubiquitylated proteins relate to AF in the left atrial appendage of patients with AF and valvular heart disease. Methods: Through LC-MS/MS analyses, we performed a study on tissues from eighteen subjects (9 with sinus rhythm and 9 with AF) who underwent cardiac valvular surgery. Specifically, we explored the ubiquitination profiles of left atrial appendage samples. Results: In summary, after the quantification ratios for the upregulated and downregulated ubiquitination cutoff values were set at >1.5 and <1:1.5, respectively, a total of 271 sites in 162 proteins exhibiting upregulated ubiquitination and 467 sites in 156 proteins exhibiting downregulated ubiquitination were identified. The ubiquitylated proteins in the AF samples were enriched in proteins associated with ribosomes, hypertrophic cardiomyopathy (HCM), glycolysis, and endocytosis. Conclusions: Our findings can be used to clarify differences in the ubiquitination levels of ribosome-related and HCM-related proteins, especially titin (TTN) and myosin heavy chain 6 (MYH6), in patients with AF, and therefore, regulating ubiquitination may be a feasible strategy for AF.

Dietary fruits and vegetables and risk of cardiovascular diseases in elderly Chinese.

BACKGROUND: Evidence regarding the potential effect of fruit and vegetable consumption on cardiovascular diseases (CVD) was limited and inconsistent among Asian people. METHODS: We prospectively examined associations of fruit and vegetable consumption with the risk of CVD among 9740 participants aged 65 years and older (mean baseline age: 88 years) in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (2008-2018). Dietary data were collected using a validated food frequency questionnaire. RESULTS: During 37 366 person-years of follow-up, a total of 3738 CVD cases were recorded. After adjusting for demographics, dietary, lifestyle and economical social factors, higher intakes of total fruits and vegetables were associated with lower risk of CVD [comparing with extreme quintiles, hazard ratio and 95% confidence interval: 0.84 (0.74, 0.95)]. The inverse association was mainly driven by vegetable consumption [0.86 (0.77, 0.95)]. Furthermore, the inverse association was stronger for the risk of hypertension [0.84 (0.72, 0.98)]. These associations were consistent across age, sex, body mass index, residence, exercise status, smoking, drinking, meat intake, modified hPDI and health status. CONCLUSIONS: This study suggests higher intakes of total fruits and vegetables are associated with a lower risk of CVD among elderly Chinese people, supporting the current recommendations of increasing fruit and vegetable consumption as part of a healthy diet for the prevention of CVD.

Research progress in the cardiac lymphatic system and myocardial repair after myocardial infarction. / å¿ƒè„æ·‹å·´ç³»ç»Ÿä¸Žå¿ƒè‚Œæ¢—æ­»åŽå¿ƒè‚Œä¿®å¤çš„ç ”ç©¶è¿›å±•.

The lymphatic system of the heart plays an important role in the repair process after myocardial injury and may regulate normal tissue homeostasis and natural regeneration via maintaining fluid homeostasis and controlling the inflammatory response. The lymphatic system in the heart is activated after myocardial injury and is involved in the scarring process of the heart. Recent studies on the lymphatic system and myocardial repair of the heart have developed rapidly, and the mechanisms for lymphangiogenesis and lymphatic endothelial cell secretion have been elucidated by different animal models. A deep understanding of the structural, molecular, and functional characteristics of the lymphatic system of the heart can help develop therapies that target the lymphatic system in the heart. Summarizing the progress in studies on targets related to myocardial repair and the cardiac lymphatic system is helpful to provide potential new targets and strategies for myocardial repair therapy after myocardial infarction.

Septal radioablation therapy for patients with hypertrophic obstructive cardiomyopathy: first-in-human study.

Aims: There is still no non-invasive septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM). This study aimed to investigate the feasibility, safety, and efficacy of stereotactic body radiotherapy (SBRT) in patients with drug-refractory symptomatic HOCM. Methods and results: The radiation target of ventricular septum was determined by multiple anatomical imaging. Stereotactic body radiotherapy was performed with standard techniques. Patients were treated with a single fraction of 25 Gy, followed up at 1, 3, 6, and 12 months by clinical visit. Five patients were enrolled and completed the 12 months follow-up. The mean radioablation time was 21.6 min, and the mean target volume was 10.5 cm3. All five patients survived and showed improvements in symptoms after SBRT. At 12 months post-SBRT, the echocardiography-derived left ventricular outflow tract gradient decreased from 88 mmHg (range, 63-105) to 52 mmHg (range, 36-66) at rest and from 101 mmHg (range, 72-121) to 74 mmHg (range, 65-100) after Valsalva. The end-diastolic thickness of the targeted septum reduced from 23.7 mm (range, 20.3-29) to 22.4 mm (range, 19.7-26.5); 6 min walking distance increased from 190.4 m (range, 50-370) to 412.0 m (range, 320-480). All patients presented with new fibrosis in the irradiated septum area. No radiation-related complications were observed during SBRT and up to 12 months post procedure. Conclusion: The current study suggests that SBRT might be a feasible radioablation therapeutic option for patients with drug-refractory symptomatic HOCM. Trial registration: ClinicalTrials.gov Identifier: NCT04686487.

From bench to bedside: The promise of sotatercept in hematologic disorders.

Sotatercept (ACE-011) is an activin receptor IIA-Fc (ActRIIA-Fc) fusion protein currently under investigation for its potential in the treatment of hematologic diseases. By impeding the activities of the overexpressed growth and differentiation factor 11 (GDF11), activin A, and other members of the transforming growth factor-ß (TGF-ß) superfamily, commonly found in hematologic disorders, sotatercept aims to restore the normal functioning of red blood cell maturation and osteoblast differentiation. This action is anticipated to enhance anemia management and hinder the progression of myeloma. Simultaneously, comprehensive research is ongoing to investigate sotatercept's pharmacokinetics and potential adverse reactions, thus laying a robust foundation for its prospective clinical use. In this review, we provide a detailed overview of TGF-ß pathways in physiological and hematologic disorder contexts, outline the potential mechanism of sotatercept, and delve into its pharmacokinetics and clinical research advancements in various hematologic diseases. A particular emphasis is given to the relationship between sotatercept dosage and its efficacy or associated adverse reactions.

Analyses of m6A regulatory genes and subtype classification in atrial fibrillation.

Objective: To explore the role of m6A regulatory genes in atrial fibrillation (AF), we classified atrial fibrillation patients into subtypes by two genotyping methods associated with m6A regulatory genes and explored their clinical significance. Methods: We downloaded datasets from the Gene Expression Omnibus (GEO) database. The m6A regulatory gene expression levels were extracted. We constructed and compared random forest (RF) and support vector machine (SVM) models. Feature genes were selected to develop a nomogram model with the superior model. We identified m6A subtypes based on significantly differentially expressed m6A regulatory genes and identified m6A gene subtypes based on m6A-related differentially expressed genes (DEGs). Comprehensive evaluation of the two m6A modification patterns was performed. Results: The data of 107 samples from three datasets, GSE115574, GSE14975 and GSE41177, were acquired from the GEO database for training models, comprising 65 AF samples and 42 sinus rhythm (SR) samples. The data of 26 samples from dataset GSE79768 comprising 14 AF samples and 12 SR samples were acquired from the GEO database for external validation. The expression levels of 23 regulatory genes of m6A were extracted. There were correlations among the m6A readers, erasers, and writers. Five feature m6A regulatory genes, ZC3H13, YTHDF1, HNRNPA2B1, IGFBP2, and IGFBP3, were determined (p < 0.05) to establish a nomogram model that can predict the incidence of atrial fibrillation with the RF model. We identified two m6A subtypes based on the five significant m6A regulatory genes (p < 0.05). Cluster B had a lower immune infiltration of immature dendritic cells than cluster A (p < 0.05). On the basis of six m6A-related DEGs between m6A subtypes (p < 0.05), two m6A gene subtypes were identified. Both cluster A and gene cluster A scored higher than the other clusters in terms of m6A score computed by principal component analysis (PCA) algorithms (p < 0.05). The m6A subtypes and m6A gene subtypes were highly consistent. Conclusion: The m6A regulatory genes play non-negligible roles in atrial fibrillation. A nomogram model developed by five feature m6A regulatory genes could be used to predict the incidence of atrial fibrillation. Two m6A modification patterns were identified and evaluated comprehensively, which may provide insights into the classification of atrial fibrillation patients and guide treatment.

A case report of multiple artery pseudoaneurysms associated with SARS-CoV-2.

Arterial pseudoaneurysms are rare vascular abnormalities that can occur as a complication of infections. Artery pseudoaneurysms associated with SARS-CoV-2 are a rare occurrence in COVID-19 patients, and their rupture can result in significant hemorrhage and sudden death. Few cases of SARS-CoV-2-associated artery pseudoaneurysms have been reported, and their underlying pathophysiological mechanisms remain unclear. This study presents the first reported case of a patient who developed both pulmonary and gallbladder artery pseudoaneurysms following SARS-CoV-2 infection. We investigate the potential pathogenesis of these pseudoaneurysms and aim to improve the understanding of this rare complication.

Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials.

OBJECTIVES: To evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. STUDY DESIGN: We extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. MAIN OUTCOME MEASURES: Hazard ratios (HRs) were used to calculate summary statistics. RESULTS: In this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76-1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54-1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74-0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56-0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69-1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40-1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12-1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06-1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41-2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48-6.56; p = 0.40) at baseline. CONCLUSIONS: Intensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome.

Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome: The H-REPLACE Randomized Equivalence and Noninferiority Trial.

Importance: Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown. Objective: To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS. Design, Setting, and Participants: This multicenter, prospective, open-label, active-controlled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022. Interventions: Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days. Main Outcomes and Measures: The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up. Results: Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%)in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group. Conclusions and Relevance: In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes. Trial Registration: ClinicalTrials.gov Identifier: NCT03363035.