Despite improvements in the secondary prevention of atherothrombosis in patients with coronary artery disease during the past decade, it is estimated that approximately 19 million people annually die from cardiovascular diseases worldwide. Atherothrombosis remains the core pathobiology of acute complications including myocardial infarction (MI), and therefore, antithrombotic therapy plays a pivotal role in the strategies for major adverse cardiovascular event (MACE) prevention. Unlike early antithrombotic management after acute coronary syndrome, less evidence is available on long-term antithrombotic therapy in patients with chronic coronary syndrome (CCS). In addition, greater recognition of the impact of bleeding complications of such therapies has led to a more complex and personalized approach to their application. The purpose of this article is to review the available evidence on long-term antithrombotic therapy in patients with CCS including those with high-risk characteristics such as prior MI or polyvascular disease.

A comprehensive literature review was performed in major databases including PubMed, Embase, and the Cochrane Library. The main focus of this narrative review was on available data from guidelines, meta-analysis, randomized controlled trials, and observational studies that assessed the efficacy and safety profile of long-term antithrombotic therapy in patients with CCS.

Several studies suggest that long-term antithrombotic therapy is effective in reducing the risk of recurrent MACEs in patients with CCS. Current clinical guidelines recommend single antiplatelet therapy with aspirin as a first-line long-term strategy for patients without indication for oral anticoagulation. However, novel approaches focused on P2Y12 inhibitor monotherapy are emerging. More intensive antithrombotic strategies including long-term dual antiplatelet therapy and dual pathway inhibition further reduce ischemic risk but at the cost of increased bleeding.

This review highlights the importance of close monitoring and regular reassessment of the risk-benefit balance of antithrombotic therapy in patients with CCS. Overall, long-term antithrombotic therapy with either single antiplatelet therapy or dual antiplatelet therapy/dual pathway inhibition is effective in reducing the risk of MACEs in patients with CCS. The choice of antithrombotic therapy should be individualized based on the patient's clinical profile, particularly for thrombohemorrhagic risk. Future research should focus on identifying the optimal antithrombotic regimen for specific subgroups of patients with prior MI particularly for those with high bleeding risk.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

As the life expectancy of individuals with hemophilia continues to increase, the complexity of balancing bleeding risks and thrombotic management has become increasingly critical in people with hemophilia with or at a high risk of thrombosis. Advances in hemophilia therapies such as extended half-life coagulation factors, non-factor therapies, rebalancing agents, and gene therapy have expanded treatment options for a variety of people with hemophilia. The thrombotic risk of people with hemophilia in general are relatively low as compared to those without hemophilia. However, antithrombotic therapy for prevention and treatment for thrombosis should still be considered in some situations, even in hemophilia. This clinical focus highlights the use of antithrombotic therapy in the management of thrombosis in people with hemophilia. A multidisciplinary, personalized approach is essential for optimizing the safety and efficacy of antithrombotic therapy in people with hemophilia with or at a high risk of thrombosis. High performance computer based multidimensional data analysis may help in establishing the personalized antithrombotic therapy in the future.

Background: Dual-pathway inhibition (DPI) with aspirin and rivaroxaban exhibited a net clinical benefit for patients with cardiovascular disease in the randomized COMPASS trial. The non-observational, international XATOA registry showed that the COMPASS results can be reproduced in clinical practice in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Here we report patient characteristics and clinical outcomes for the subgroup of German PAD patients of the XATOA registry and compare them to COMPASS PAD patients. Patients and methods: XATOA was an international prospective registry of patients receiving DPI with a mean follow-up period of 15 months. The subgroup of German patients with PAD in XATOA comprised 1,819 patients, of which 925 patients (50.9%) had only PAD and 894 patients (49.1%) had both CAD and PAD. Patient characteristics such as prior medical history and prior medications as well as clinical outcomes such as incidences of major adverse limb events (MALE), major adverse cardiovascular events (MACE) and major bleeding events were assessed. Results: DPI was well-tolerated in clinical practice. Patient characteristics and clinical outcomes especially for patients with only PAD differed from characteristics and outcomes of the overall German XATOA population as well as the PAD subgroup of COMPASS. Patients with only PAD were markedly less supplied with lipid-lowering agents and betablockers. Incidences of MALE were high in German PAD patients of XATOA (9.0%) and markedly higher than in the PAD subgroup of COMPASS (1.2%). Incidences of MACE and major bleeding events were lower in German PAD patients of XATOA (MACE: 2.9%, major bleeding: 1.4%) than in PAD patients of COMPASS (MACE: 5.1%, major bleeding: 3.1%). Conclusions: DPI with rivaroxaban and aspirin is well-tolerated by PAD patients in German clinical practice. PAD patients in Germany exhibit different characteristics and show a different clinical outcome profile than PAD patients in COMPASS.

Background During neurointerventional treatment of intracranial aneurysms (IAs), poor antiplatelet drug response increases the risk of a cerebral ischemic event (IE). Replacing clopidogrel with ticagrelor may reduce this risk. Purpose To determine whether platelet function test (PFT)-guided antiplatelet therapy reduces incidence of IEs compared with standard dual antiplatelet therapy (SDAT; daily oral aspirin and clopidogrel, 100 mg and 75 mg, respectively) in patients undergoing endovascular intervention for IAs. Materials and Methods In this prospective, multicenter, cluster-randomized trial, 16 neurointerventional teams were randomly allocated to eight test and eight control clusters. Between May and August 2023, test group participants underwent PFT. Test group participants who showed poor antiplatelet response were administered an increased aspirin dose or were switched from clopidogrel to ticagrelor. The control group was administered SDAT. The primary outcome was any cerebral IE within 30 days after the procedure. The exploratory outcomes were any IE within 7 days, modified Rankin Scale score, and all-cause mortality within 30 days. The safety outcome measure was any bleeding event within 30 days. All outcome analyses were performed using generalized linear mixed-effects models. Results A total of 590 participants were included (median age, 58 years; 374 women). IE incidence within 30 days was lower in the test group than in the control group (6.8% [20 of 295] vs 13.2% [39 of 295]; odds ratio [OR], 0.54; 95% CI: 0.31, 0.94; P = .03) and within 7 days (4.1% [12 of 295] vs 10.8% [32 of 295]; OR, 0.48; 95% CI: 0.25, 0.89; P = .02) after undergoing the procedure. There was no evidence of a difference between the test group and the control group in modified Rankin Scale scores (0.33 vs 0.49, respectively; P = .11) or mortality (0.3% [one of 295] vs 2.0% [six of 295], respectively; P = .54). Furthermore, there was no evidence of a between-group difference in bleeding event incidence (24.1% [71 of 295] vs 31.2% [92 of 295]; OR, 0.67; 95% CI: 0.30, 1.5; P = .32). Conclusion PFT-guided antiplatelet therapy was associated with reduced IE incidence. Administration of 60 mg of ticagrelor did not increase bleeding event incidence. Clinicaltrials.gov Identifier: NCT05825391 © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Kallmes and Altschul in this issue.

Low-dose aspirin and rivaroxaban are the cornerstone treatment for cardiovascular prevention in patients with peripheral artery disease (PAD) and/or stable coronary artery disease (SCAD). The combination of rivaroxaban with aspirin imposes a synergistic effect on the inhibition of factor-induced platelet aggregation. The present work aimed at comparing the cost-utility and cost-effectiveness of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban alone (5 mg twice daily) with aspirin alone in patients with peripheral artery disease (PAD) or coronary artery disease (CAD) and related subgroups.

This pharmacoeconomic study was performed based on the insurance organization and utilized a state-transition decision Markov model. From the COMPASS trial, Clinical efficacy and Clinical events were collected. Health outcomes and cost were assessed over a 20-year time horizon (lifetime). The direct costs of medical services were included in the analysis. The results were stated based on Incremental Cost-Utility (ICUR) and Incremental Cost Effectiveness Ratio (ICER). Uncertainty was assessed utilizing deterministic and probabilistic sensitivity analyses. Discount rates of .058 and .03 were included for cost and effectiveness data, respectively. The budget impact based on the Markov model was estimated as the financial burden resulting from the insurance coverage of rivaroxaban.

In the total of CAD and PAD patients, treatment with rivaroxaban plus aspirin and rivaroxaban alone were more expensive than the aspirin alone, but also more effective, resulting in ICUR being $4594/QALY and $13601/QALY respectively, and for ICER being $3348/LYG and $9901/LYG. In PAD patients rivaroxaban plus aspirin had higher effectiveness than aspirin alone that ICUR and ICER being $11929/QALY and $9896/LYG respectively. In CAD patients, treatment with rivaroxaban plus aspirin was expensive and less effective than aspirin alone. The estimated annual budget impact was $28,253,135 for the rivaroxaban plus aspirin and $292,593,909 for the rivaroxaban alone in the total of CAD and PAD patients.

This study showed that rivaroxaban plus aspirin is a cost-effective alternative in PAD and total of CAD and PAD patients. In CAD patients, rivaroxaban plus aspirin and rivaroxaban alone were not cost-effective.

The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" incorporates new evidence since the "2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction" and the corresponding "2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes" and the "2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction." The "2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes" and the "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization" retire and replace, respectively, the "2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease."

A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

De-escalation of dual antiplatelet (DAPT) intensity may be considered in patients with high risk of bleeding after acute coronary syndrome. Some high risk patients after de-escalation may require antithrombotic therapy prolonged over 12 months. With the current guideline recommended strategies, there are some doubts and uncertainties with respect to the transition period. Herein we discuss these issues more extensively. De-escalation of DAPT, intended to decrease bleeding risk, may be accomplished by switching to a drug with reduced antiplatelet effect (de-escalation by switching), by reducing the dose (de-escalation by dose reduction), or by removing an antiplatelet agent (de-escalation by discontinuation). The dilemma concerns patients who have undergone scheduled, early de-escalation of DAPT to monotherapy with a P2Y12 receptor inhibitor at standard dose, as in the TWILIGHT study. The dilemma is even greater in patients whose de-escalation consisted of both reduction in dose of one and discontinuation of the other antiplatelet agent. This strategy is currently being tested in the ELECTRA-SIRIO 2 study. When making a therapeutic decision in patients who meet the criteria for prolonged dual antithrombotic therapy we suggest considering the previously applied DAPT de-escalation strategy. In general, unless the risk of ischemic events has increased since prior de-escalation, there is no scientific rationale for escalating antithrombotic treatment in a patient previously de-escalated (through reduction or discontinuation). Regardless of the treatment strategy, its effectiveness depends on the patient's adherence to medical recommendations.

The care of elderly patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCIs) presents unique challenges due to age-related physiological and functional changes. With the global population aging rapidly, this demographic change affects a growing proportion of individuals requiring PCI. However, advanced age is associated with increased susceptibility to ischemic and bleeding complications, driven by physiological changes such as altered coagulation, vascular stiffness, and declining organ function. These factors complicate the management of CAD, making the balance between reducing thrombotic events and minimizing bleeding risks particularly challenging. Antiplatelet therapy is central to post-PCI management, but its benefits and risks differ significantly in elderly patients compared to younger populations. Tools like the PRECISE-DAPT and ARC-HBR provide guidance on dual antiplatelet therapy duration and bleeding risk stratification. However, their applicability and predictive accuracy in elderly patients remain areas of active investigation. This underscores the need for improved risk assessment methods tailored to the unique needs of aging individuals. In this review, we explore the epidemiological, pathophysiological, and clinical aspects of CAD in elderly patients, emphasizing the impact of aging on disease presentation and outcomes. Furthermore, we assess current risk stratification tools and discuss their limitations in predicting adverse events in older populations. By synthesizing these insights, we aim to highlight the complexities of managing elderly CAD patients and identify opportunities for optimizing personalized care to achieve better outcomes in this vulnerable group.

Antithrombotic drugs are widely used to prevent thrombotic events in patients with cardiovascular diseases. However, they all carry varying degrees of bleeding risk. Currently, there are no approved reversal agents for antiplatelet medications, which limits their further clinical application and poses challenges in managing bleeding complications. In this proof-of-concept study, we explore the feasibility of a reversal agent system using ticagrelor and a corresponding liposome-based antidote. Specifically, we developed an azide-functionalized ticagrelor derivative (Tic-N3) and a clickable DBCO-modified liposome (Lipo-DBCO) to enable controlled reversal of antiplatelet activity. Our findings demonstrate that the azide modification does not compromise the antiplatelet efficacy and biocompatibility of ticagrelor. The antiplatelet effects of Tic-N3 were successfully reversed by Lipo-DBCO, as validated through platelet aggregation assays and in vivo mouse models of tail bleeding and liver injury. Additionally, we investigated the thiol-maleimide pairing as an alternative system, enhancing the versatility of our approach. This strategy reveals the possibility and clinical application prospects of antiplatelet drug reversal agents, offering a promising solution for the safe management of bleeding risks associated with antiplatelet therapy.

Aspirin is commonly utilized in the management and prevention of various diseases. However, in specific individuals, particularly those with low body mass index (BMI), aspirin can elevate the risk of bleeding. Achieving a delicate equilibrium between the desirable antiplatelet effects and potential bleeding complications is a notable consideration. The objective of this study was to create a novel bleeding risk prediction tool for aspirin users with a low BMI. A total of 2436 aspirin users with a low BMI were included in this study conducted at the Affiliated Dongyang Hospital of Wenzhou Medical University. Patient data, comprising demographics, clinical characteristics, comorbidities, medical history, and laboratory tests, were collected. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation purposes. The identification of clinically significant features associated with bleeding was achieved through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression and boruta analysis. Subsequently, these important features underwent multivariate logistic regression analysis. Based on independent bleeding risk factors, a logistic regression model was constructed and presented as a nomogram. Model performance was evaluated using metrics such as the area under the curve (AUC), calibration curves, decision curve analysis (DCA), clinical impact curve (CIC), and net reduction curve (NRC) in both the training and testing sets. LASSO analysis identified two clinical features, while Boruta analysis identified nine clinical features out of a total of 21 features. Subsequent multivariate logistic regression analysis selected significant independent risk factors. The boruta model, which demonstrated the highest AUC, consisted of six clinical variables: hemoglobin, platelet count, previous bleeding, tumor, smoke, and diabetes mellitus. These variables were integrated into a visually represented nomogram. The model exhibited an AUC of 0.832 (95% CI: 0.788-0.875) in the training dataset and 0.775 (95% CI: 0.698-0.853) in the test dataset, indicating excellent discriminatory performance. Calibration curve analysis revealed close alignment with the ideal curve. Furthermore, DCA, CIC, and NRC demonstrated favorable clinical net benefit for the model. This study has successfully created a novel risk prediction tool specifically designed for aspirin users with a low BMI. This tool enables the stratification of low BMI patients based on their anticipated bleeding risk.

The potential benefits of P2Y12 inhibitor deescalation for acute myocardial infarction after percutaneous coronary intervention may be influenced by body mass index (BMI).

To investigate the association of BMI on deescalation outcomes after 12 months in patients with acute myocardial infarction after percutaneous coronary intervention who were initially treated with aspirin plus ticagrelor for 1 month, and to assess whether BMI-based switching from aspirin plus ticagrelor (active control strategy) to aspirin plus clopidogrel (deescalation strategy) is associated with individualized benefits.

This study is a post hoc analysis, based on BMI, of data from the TALOS-AMI (Ticagrelor vs Clopidogrel in Stabilized Patients with Acute Myocardial Infarction) randomized clinical trial. Data were collected from February 14, 2014, to December 31, 2018, with follow-up to January 21, 2021. Analyses were conducted from December 1, 2021, to August 21, 2024. Among 2697 trial participants from 32 centers in South Korea, 2686 participants whose BMI data were available were included.

All patients received aspirin plus ticagrelor for 1 month after percutaneous coronary intervention. Stabilized patients were then randomized to either the active control or deescalation strategy for an additional 11 months.

The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2, 3, or 5 at 12 months after percutaneous coronary intervention. The trial compared the active control and deescalation strategies according to BMIs, including an interaction test.

Of the 2686 patients included (mean [SD] age, 60.0 [11.4] years; 2234 [83.2%] male), 2344 (1161 in the deescalation group and 1183 in the active control group) had a BMI less than 28, and 342 (184 in the deescalation group and 158 in the active control group) had a BMI of 28 or greater. The deescalation strategy was associated with significantly reduced composite outcomes compared with the active control strategy in the group with a BMI less than 28 (53 [4.6%] vs 98 [8.3%]; adjusted hazard ratio, 0.54; 95% CI, 0.39-0.76; P < .001), primarily due to fewer bleeding complications. There was no association in the group with a BMI of 28 or greater (6 [3.3%] vs 5 [3.2%]; adjusted hazard ratio, 1.07; 95% CI, 0.33-3.50; P = .91).

In this post hoc analysis of the TALOS-AMI randomized clinical trial, in stabilized patients with acute myocardial infarction, an unguided deescalation strategy of switching from ticagrelor to clopidogrel after 1 month was associated with better clinical outcomes in those with lower BMIs.

ClinicalTrials.gov Identifier: NCT02018055.

Advances in pharmacotherapy for coronary thrombosis treatment and prevention have transformed the clinical outcomes of patients with coronary artery disease but increased the complexity of therapeutic decision-making. Improvements in percutaneous coronary intervention techniques and stent design have reduced the incidence of thrombotic complications, which consequently has increased the challenge of adequately powering clinical trials of novel antithrombotic strategies for efficacy outcomes. Knowledge of the pathophysiology of coronary thrombosis and the characteristics of antithrombotic drugs can help with therapeutic decisions.

This review covers the pathophysiology of coronary thrombosis and the mechanisms of action of drugs developed for its treatment, provides an overview of the key issues in decision-making, and highlights key areas for further work in order to guide clinicians on how to individualize risk management and address gaps in the evidence base.

Individualization of antithrombotic therapy regimens has become a vital part of optimizing risk management in people with coronary thrombosis. A critical appraisal of the strengths and limitations of available drugs and the evidence supporting the use of different antithrombotic combinations is intended to provide direction to clinicians and point the way toward further improvements in pharmacotherapy for coronary thrombosis treatment and prevention.

Ticagrelor, an effective antiplatelet for acute coronary syndrome (ACS), may elevate serum uric acid (SUA), potentially causing gout. This study aims to identify risk factors for ticagrelor-induced in-hospital gout in patients with ACS and create a predictive model for clinical use.A total of 1164 patients with ACS treated with ticagrelor (n = 640) or clopidogrel (n = 524) were retrospectively analyzed. The incidence of in-hospital gout and changes in SUA levels were compared between the groups. Patients with ticagrelor were further divided into gout and non-gout groups to identify risk factors using logistic regression. A nomogram model was constructed based on significant risk factors.The incidence of in-hospital gout was significantly higher in patients with ticagrelor than in patients with clopidogrel (9.8% versus 1.9%, P < 0.001). There were significant differences in SUA levels between the groups. Logistic regression revealed alcohol consumption, total cholesterol, and baseline SUA as independent risk factors for gout. A nomogram model was developed and demonstrated good predictive accuracy.Ticagrelor was associated with a higher risk of in-hospital gout than clopidogrel in patients with ACS. Alcohol use, total cholesterol, and baseline uric acid are key risk factors. The nomogram model developed in this study can assist in predicting the risk of in-hospital gout in patients with ACS treated with ticagrelor.

Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA).

A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage.

Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889).

Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA.

There is a lack of consensus regarding the optimal antithrombotic therapy (ATT) after popliteal and infrapopliteal (PIP) endovascular therapy (EVT). Currently, dual antiplatelet therapy (DAPT) for 3 months and single antiplatelet therapy (SAPT) are the most prescribed regimens in the Netherlands. Thus far, no randomized comparison has been performed on the optimal ATT approach. Therefore, this study compared the efficacy and safety of 3-month DAPT with SAPT following PIP EVT.

Retrospective analysis of prospectively collected data from a multicenter registry.

The Dutch chronic lower limb-threatening ischemia registry (THRILLER) collected prospective data on patients enrolled between January 2021 and October 2023. As for ATT, only patients prescribed antiplatelet therapy (APT), were included in this analysis. The primary efficacy outcome was a composite of 3-month major adverse cardiovascular events (MACEs, ie, myocardial infarction, cerebrovascular event, cardiovascular death), major adverse limb events (MALEs, ie, major amputation, reintervention), and non-cardiovascular death. Secondary efficacy outcomes were 3-month MACE, MALE, and all-cause mortality. The primary safety outcome was major bleeding according to the 'Thrombolysis In Myocardial Infarction' (TIMI) classification. Descriptive statistics and Cox proportional hazard models were applied.

In total, 460 of 840 THRILLER patients used DAPT or SAPT as ATT and were therefore included in the analysis. Of these, 322 (70%) received DAPT and 138 (30%) received SAPT. In total, 73 (15.9%) primary efficacy outcomes were observed of which 21 (15.2%) events in the SAPT group and 52 (16.1%) events in the DAPT group. No significant differences were observed between SAPT and DAPT for the primary efficacy outcomes or any of the secondary efficacy outcomes. In both groups, one case of major bleeding was observed.

The findings suggest that 3 months of DAPT is not superior to SAPT. A well-powered randomized trial is warranted to assess the efficacy and safety of post-procedural DAPT in chronic limb-threatening ischemia (CLTI) patients undergoing PIP EVT.

This manuscript reports on the efficacy and safety outcomes of 3 months of DAPT versus SAPT, which are commonly chosen therapies following popliteal and infrapopliteal endovascular therapy. No significant difference was found between the two groups regarding major adverse cardiovascular events, all-cause death, major amputation, or major bleeding. Therefore, 3 months of DAPT does not seem superior to SAPT. These results suggest that SAPT appears to be a sufficient alternative when considering 3 months of DAPT. Further research should verify these outcomes and focus on the efficacy and safety of prolonged DAPT suppletion after endovascular therapy.

This review examines current evidence on pharmacologically induced plaque stabilization in the context of a growing range of new therapies. It explores the potential for a paradigm shift in atherosclerotic cardiovascular disease (ASCVD) prevention, where treatments may not need to be lifelong to achieve lasting benefits.

Since 2015, over 14 novel therapies have been introduced, each shown to reduce ASCVD risk when added to standard care with statins and aspirin. More than 80% of ischemic heart disease patients are now eligible for one or more of these treatments, increasing the risk of polypharmacy, treatment burden, and adverse side effects. As more therapies become available, this challenge is expected to grow. Many of these treatments have demonstrated plaque regression and stabilization, as evidenced by both intravascular ultrasound and computed tomography angiography, which likely explains much of their efficacy.

The increasing number of novel therapies presents challenges in preventing ASCVD without leading to lifelong polypharmacy and increased patient burden. Since many of these drugs act through plaque stabilization, a new approach may be feasible - using these treatments for shorter durations to induce plaque regression, followed by less intensive maintenance therapies to preserve stability. This approach warrants further investigation in future studies.

Comorbid diabetes mellitus (DM) in patients with ischemic heart disease (IHD) is a serious factor that significantly impairs the life prognosis and increases the risk of cardiovascular complications (CVC) as well as the likelihood of death. The residual risk of developing CVC in such patients is largely determined by the high thrombotic status, that is associated with hypercoagulation characteristic of DM. Hypercoagulation causes activation of both platelet and coagulation pathways, which leads to an increased susceptibility to thrombosis. In this context, the combined administration of the anticoagulant rivaroxaban (Xarelto®) 2.5 mg and acetylsalicylic acid (ASA) can significantly reduce this risk by affecting both mechanisms of thrombus formation and thereby improving the prognosis. Rivaroxaban 2.5 mg in combination with ASA is the only available strategy to intensify the antithrombotic therapy in patients with stable IHD and DM with no history of ischemic events. Importantly, such therapy should be initiated as early as possible to prevent clinically significant CVCs and improve patients' quality of life.

Cardiovascular disease (CVD) remains the most common cause of morbidity and mortality worldwide [...].

Purines are ancient metabolites with established and emerging metabolic and non-metabolic signaling attributes. The expression of purine metabolism-related genes is frequently activated in human malignancies, correlating with increased cancer aggressiveness and chemoresistance. Importantly, under certain stimulating conditions, the purine biosynthetic enzymes can assemble into a metabolon called "purinosomes" to enhance purine flux. Current evidence suggests that purine flux is regulated by a complex circuit that encompasses transcriptional, post-translational, metabolic, and association-dependent regulatory mechanisms. Furthermore, purines within the tumor microenvironment modulate cancer immunity through signaling mediated by purinergic receptors. The deregulation of purine metabolism has significant metabolic consequences, particularly hyperuricemia. Herbal-based therapeutics have emerged as valuable pharmacological interventions for the treatment of hyperuricemia by inhibiting the activity of hepatic XOD, modulating the expression of renal urate transporters, and suppressing inflammatory responses. This review summarizes recent advancements in the understanding of purine metabolism in clinically relevant malignancies and metabolic disorders. Additionally, we discuss the role of herbal interventions and the interaction between the host and gut microbiota in the regulation of purine homeostasis. This information will fuel the innovation of therapeutic strategies that target the disease-associated rewiring of purine metabolism for therapeutic applications.

Recent data question the use of aspirin as a bedrock of antiplatelet therapy in patients with arterial diseases. There are controversies regarding the efficacy of aspirin therapy with respect to specific demographic characteristics, dose and formulations, benefit in primary prevention, and duration in secondary prevention. Importantly, to balance the ischemic benefits and the risk of excessive bleeding following a coronary event, recent studies have investigated strategies to discontinue aspirin therapy and continue with P2Y12 receptor inhibitor monotherapy. However, the precise time when to discontinue aspirin is still unresolved.

Evidence from recent studies evaluating the role of aspirin in primary and secondary prevention studies was collected from a selective literature search. In this review, the authors discuss current recommendations, large-scale studies of aspirin therapy, controversies, and potential future opportunities for aspirin therapy.

With the new evidence showing lower bleeding risk with aspirin-free strategies in both primary and secondary prevention studies, the role of aspirin is being revaluated with P2Y12 receptor inhibitor monotherapy. The potential benefits of novel aspirin formulations and alternative delivery methods, such as inhaled aspirin, are undergoing much-needed investigation with the goal of optimizing care for a wide range of patients.

Abbreviated antiplatelet therapy (APT) reduces bleeding without increasing ischemic events in largely unselected high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI). Diabetes mellitus (DM) is associated with higher ischemic risk, and its impact on the safety and effectiveness of abbreviated APT in HBR PCI patients remains unknown.

This study sought to investigate the comparative effectiveness of abbreviated (1 month) vs standard (≥3 months) APT in HBR patients with and without DM after biodegradable polymer sirolimus-eluting coronary stent implantation.

This was a prespecified analysis from the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen) trial, which randomized 4,579 HBR patients (1,538 [34%] with DM) to abbreviated (n = 2,295) or standard (n = 2,284) APT. The coprimary outcomes were net adverse clinical events (NACEs; composite of all-cause death, myocardial infarction, stroke, and major bleeding), major adverse cardiac or cerebral events (MACCEs; all-cause death, myocardial infarction, and stroke), and major or clinically relevant nonmajor bleeding at 11 months.

HBR patients with DM had higher risks of MACCEs (HR: 1.28; 95% CI: 1.00-1.63) and similar net adverse or bleeding events compared with nondiabetic subjects. Abbreviated compared with standard APT was associated with similar NACEs and MACCEs (Pinteraction = 0.47 and 0.59, respectively) and reduced major or clinically relevant nonmajor bleeding (Pinteraction = 0.55) irrespective of diabetes status.

MACCE and NACE rates were similar, and bleeding rates were lower with abbreviated APT in patients with or without diabetes. Therefore, diabetes status did not modify the treatment effects of abbreviated vs standard APT in HBR patients after biodegradable polymer sirolimus-eluting coronary stent implantation. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With a Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Diabetes mellitus (DM) promotes atherosclerosis, leading to increased risk for cardiovascular morbidity and mortality. Diabetics represent a challenging subset of patients undergoing percutaneous coronary intervention (PCI) or who have experienced an acute coronary syndrome (ACS), a subset characterized by higher rates of recurrent ischemic events compared with non-diabetics. These events are caused by both patient-related accelerated atherosclerotic disease progression and worse stent-related adverse clinical outcomes translating into a higher risk for repeat revascularization. In addition, DM is paradoxically associated with an increased risk of major bleeding following PCI or an ACS. Secondary prevention therapies following PCI or an ACS in diabetic patients are therefore of paramount importance. This mini review focuses on the currently available evidence regarding short- and long-term secondary prevention treatments for diabetic patients undergoing PCI or who have experienced an ACS.

Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI).

PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg.

Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI.

Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients.

We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs).

Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81-0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49-0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40-1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality.

Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors.

To summarize the recent evidence and guideline recommendations on aspirin or P2Y12 inhibitor monotherapy in patients with stable ischemic heart disease and provide insights into future directions on this topic, which involves transition to a personalized assessment of bleeding and thrombotic risks.

It has been questioned whether the evidence for aspirin as the foundational component of secondary prevention in patients with coronary artery disease aligns with contemporary pharmaco-invasive strategies. The recent HOST-EXAM study randomized patients who had received dual antiplatelet therapy for 6 to 18 months without ischemic or major bleeding events to either clopidogrel or aspirin for a further 24 months, and demonstrated that the patients in the clopidogrel arm had significantly lower rates of both thrombotic and bleeding complications compared to those in the aspirin arm. The patient-level PANTHER meta-analysis showed that in patients with established coronary artery disease, P2Y12 inhibitor monotherapy was associated with lower rates of myocardial infarction, stent thrombosis as well as gastrointestinal bleeding and hemorrhagic stroke compared to aspirin monotherapy, albeit with similar rates of all-cause mortality, cardiovascular mortality and major bleeding. Long-term low-dose aspirin is recommended for secondary prevention in patients with stable ischemic heart disease, with clopidogrel monotherapy being acknowledged as a feasible alternative. Dual antiplatelet therapy for six months after percutaneous coronary intervention remains the standard recommendation for patients with stable ischemic heart disease. However, the duration of dual antiplatelet therapy may be shortened and followed by P2Y12 inhibitor monotherapy or prolonged based on individualized evaluation of the patient's risk profile.

Patients with peripheral artery disease and generalized atherosclerosis are at high risk of cardiovascular and limb complications, affecting both quality of life and longevity. Lower limb atherosclerotic disease is associated with high cardiovascular morbidity and mortality and adequate management is founded on treatments involving patient-dependent factors, such as lifestyle changes, and physician-dependent factors, such as clinical treatment, endovascular treatment, or conventional surgery. Medical management of peripheral artery disease is multifaceted, and its most important elements are reduction of cholesterol level, antithrombotic therapy, control of arterial blood pressure, control of diabetes, and smoking cessation. Adhesion to this regime can reduce complications related to the limbs, such as chronic limb-threatening ischemia, that can result in amputation, and the systemic complications of atherosclerosis, such as stroke and myocardial infarction.

Antithrombotic therapy improves endovascular intervention outcomes for peripheral artery disease. However, there are limited data guiding the choice and duration of these adjuvant therapies. Thus, we explored current antithrombotic prescribing preferences among vascular interventionalists, hypothesizing that there are varied and inconsistent treatment practices among providers.

We developed and distributed a de-identified RedCap survey via Twitter and email to Vascular Quality Initiative members (February 2023). Multiple-choice questions queried antithrombotic agents and treatment durations for a clinical vignette (a claudicant on 81 mg aspirin and statin) with different arterial disease locations (iliac, femoropopliteal, or tibial vessels) and different revascularization strategies (angioplasty or stenting, with and without drug-coating). Antithrombotic options included monotherapies with antiplatelet agents or low-dose rivaroxaban; dual therapies with aspirin combined with a P2Y12 inhibitor (dual antiplatelet therapy, DAPT) or low-dose rivaroxaban (dual pathway inhibition or DPI); or triple therapy with aspirin, a P2Y12 inhibitor, and low-dose rivaroxaban. Options for therapy duration included 30, 90, 180, and 365 days, or indefinitely.

There were 199 respondents (17% female, 68% White race, 63% academic, 88% vascular surgery). Across all treatment scenarios, respondents selected DAPT (n = 171/199; 86%) in at least one revascularization scenario, followed by aspirin monotherapy (n = 83/199; 42%) and DPI (n = 49/199; 25%). Therapy choice did differ by both anatomic location and revascularization strategy (P < .05). DAPT was most selected following femoropopliteal revascularization (n = 165/199, 83%) and bare metal stenting (n = 162/198, 82%). However, aspirin monotherapy was most selected following iliac level revascularization (n = 52/197; 26%) and following percutaneous transluminal angioplasty at any level (n = 51/182; 28%). DPI was most selected following tibial revascularization (n = 39/184; 21%) and following percutaneous transluminal angioplasty (n = 38/182; 21%). Among those who selected DAPT, the 90-day (n = 99/171; 58%) duration was preferred. Those who selected DPI favored indefinite treatment durations (n = 34/49; 69%). Indefinite DAPT and DPI therapy were more commonly selected for distal level revascularization (P < .05). Rivaroxaban utilization was limited secondary to cost (n = 108/178; 61%), lack of demonstrated effectiveness (n = 75/178; 42%), and concern for safety and bleeding (n = 27/178; 15%).

Following lower extremity endovascular treatment of peripheral artery disease, a 90-day duration of DAPT remains the most commonly selected antithrombotic regimen despite the emergence of DPI as an evidence-based antithrombotic therapy. The variability in provider preferred antithrombotic agent and treatment duration emphasizes the need for high-quality evidence for the medical optimization of revascularization outcomes.

Optimal duration and choice of antiplatelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention remain controversial.

Digital databases (PubMed, Cochrane, and Embase) were queried to select all randomized controlled trials on a post-percutaneous coronary intervention population with acute coronary syndrome. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for 12 months was compared with 4 major strategies: high-potency, high- to low-potency, low-dose, and short-duration DAPT. A network meta-analysis was performed to compare the safety and efficacy of different antiplatelet strategies. This study was the second updated manuscript under the International Prospective Register of Systematic Review registration (CRD42021286552). Thirty-two randomized controlled trials comprising 103 459 (51 750 experimental, 51 709 control) patients were included. Compared with DAPT with aspirin and clopidogrel for 12 months, high- to low-potency DAPT (risk ratio [RR], 0.69 [95% CI, 0.52-0.92]) and aspirin+prasugrel containing DAPT for 12 months (RR, 0.84 [95% CI, 0.72-0.98]) had a significantly lower, whereas DAPT for 1 month followed by clopidogrel only (RR, 1.59 [95% CI, 1.06-2.39]) had a higher, incidence of major adverse cardiovascular events at 1 year (median follow-up). Prasugrel (RR, 1.35 [95% CI, 1.09-1.66]) and ticagrelor (RR, 1.38 [95% CI, 1.17-1.62]) containing DAPT for 12 months had significantly higher rates, whereas high- to low-potency DAPT (RR, 0.85 [95% CI, 0.63-1.15]) had no significant risk of major bleeding.

Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, can be considered the optimal strategy for treating post-percutaneous coronary intervention patients with acute coronary syndrome because of a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding.

This study aimed to develop a predictive model for assessing bleeding risk in dual antiplatelet therapy (DAPT) patients.

A total of 18,408 DAPT patients were included. Data on patients' demographics, clinical features, underlying diseases, past history, and laboratory examinations were collected from Affiliated Dongyang Hospital of Wenzhou Medical University. The patients were randomly divided into two groups in a proportion of 7:3, with the most used for model development and the remaining for internal validation. LASSO regression, multivariate logistic regression, and six machine learning models, including random forest (RF), k-nearest neighbor imputing (KNN), decision tree (DT), extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), and Support Vector Machine (SVM), were used to develop prediction models. Model prediction performance was evaluated using area under the curve (AUC), calibration curves, decision curve analysis (DCA), clinical impact curve (CIC), and net reduction curve (NRC).

The XGBoost model demonstrated the highest AUC. The model features were comprised of seven clinical variables, including: HGB, PLT, previous bleeding, cerebral infarction, sex, Surgical history, and hypertension. A nomogram was developed based on seven variables. The AUC of the model was 0.861 (95% CI 0.847-0.875) in the development cohort and 0.877 (95% CI 0.856-0.898) in the validation cohort, indicating that the model had good differential performance. The results of calibration curve analysis showed that the calibration curve of this nomogram model was close to the ideal curve. The clinical decision curve also showed good clinical net benefit of the nomogram model.

This study successfully developed a predictive model for estimating bleeding risk in DAPT patients. It has the potential to optimize treatment planning, improve patient outcomes, and enhance resource utilization.

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.