Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial.

BACKGROUND: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS. METHODS: CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors. RESULTS: The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; P=0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; P<0.01). The P value was 0.56 for the treatment × ESUS status interaction effect. CONCLUSIONS: In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles and were classified as ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

[IDEN Consensus on Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy].

Antithrombotic agents, including antiplatelet agent and anticoagulants are widely used in Korea due to increasing incidence of cardio-cerebrovascular disease and aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. Clinical practice guideline regarding this issue which was developed by the Korean Society of Gastrointestinal Endoscopy was published in 2020. However, since then, new evidence has emerged for the use of dual antiplatelet therapy and direct anticoagulant management, and revised guidelines were issued in the US and Europe. Accordingly, the previous guidelines were revised, cardiologists also participated in the development group, and the recommendations went through a consensus process among international experts. This guideline presents 14 recommendations made according to the Grading of Recommendations, Assessment, Development, and Evaluation methodology, and was reviewed by multidisciplinary experts. This guideline provides useful information that can assist endoscopists in the management of patients on antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

[Aspirin and prevention of the recurrence of venous thromboembolism]. / Aspirine et prévention de la récidive de la maladie veineuse thromboembolique.

After a first episode of unprovoked vein thrombosis, the risk of recurrence persists for many years. Long term of anticoagulant therapy prevents the recurrence of vein thrombosis but is associated with a major risk of bleeding. As platelets play a role in the initiation and propagation of venous thromboembolism as well, antiplatelet agents, may play a role in the treatment and prevention of this disease. This review summarizes available evidence on effect of aspirin in the prevention of recurrent deep vein thrombosis.

Antithrombotic therapy after heart valve surgery: contemporary practice in the UK.

OBJECTIVES: There is a lack of high-quality data informing the optimal antithrombotic drug strategy following bioprosthetic heart valve replacement or valve repair. Disparity in recommendations from international guidelines reflects this. This study aimed to document current patterns of antithrombotic prescribing after heart valve surgery in the UK. METHODS: All UK consultant cardiac surgeons were e-mailed a custom-designed survey. The use of oral anticoagulant (OAC) and/or antiplatelet drugs following bioprosthetic aortic valve replacement or mitral valve replacement, or mitral valve repair (MVrep), for patients in sinus rhythm, without additional indications for antithrombotic medication, was assessed. Additionally, we evaluated anticoagulant choice following MVrep in patients with atrial fibrillation. RESULTS: We identified 260 UK consultant cardiac surgeons from 36 units, of whom 103 (40%) responded, with 33 units (92%) having at least 1 respondent. The greatest consensus was for patients undergoing bioprosthetic aortic valve replacement, in which 76% of surgeons favour initial antiplatelet therapy and 53% prescribe lifelong treatment. Only 8% recommend initial OAC. After bioprosthetic mitral valve replacement, 48% of surgeons use an initial OAC strategy (versus 42% antiplatelet), with 66% subsequently prescribing lifelong antiplatelet therapy. After MVrep, recommendations were lifelong antiplatelet agent alone (34%) or following 3 months OAC (20%), no antithrombotic agent (20%), or 3 months OAC (16%). After MVrep for patients with established atrial fibrillation, surgeons recommend warfarin (38%), a direct oral anticoagulant (37%) or have no preference between the 2 (25%). CONCLUSIONS: There is considerable variation in the use of antithrombotic drugs after heart valve surgery in the UK and a lack of high-quality evidence to guide practice, underscoring the need for randomized studies.

Preoperative aspirin and anticoagulants do not affect partial nephrectomy bleeding.

INTRODUCTION: Studies have reached mixed conclusions on the role of antiplatelet and anticoagulant agents on postoperative complications of partial nephrectomies. This study examines whether preoperative anticoagulation use affected the risk of hemorrhagic complications after partial nephrectomy. MATERIALS AND METHODS: This is a retrospective chart review of all partial nephrectomies performed between 2017 and 2022 at a single institution. For each operation, preoperative data was gathered on whether the patient was on anticoagulation, the type and dose of anticoagulation, and how many days the anticoagulation was held preoperatively. Bivariate analyses for continuous measures were performed using Student's t-tests when there were two comparison groups and ANOVA models when there were more than two comparison groups and Chi-Square tests were used for categorical variables, with Fisher's Exact being used when expected cell counts were small. RESULTS: In this study, warfarin was held for an average of 5.43 days, clopidogrel was held for an average of 6.60 days, aspirin was held for an average of 7.65 days, and direct oral anticoagulants (DOACs) were held for an average of 4.00 days. There was no significant difference in hemoglobin (Hb) change, rate of intraoperative transfusion, postoperative transfusion, bleeding complication, pseudoaneurysm rate, or additional bleeding processes between patients on prior anticoagulation therapy and those not on therapy. There was no significant difference in intraoperative or postoperative outcomes based on history of aspirin use and continuation of aspirin through the surgery. While estimated blood loss appeared statistically significant initially, this difference was accounted for by the covariates of comorbidities, RENAL score, surgical approach, and type of renorrhaphy. Overall, there was no difference in complication rate based solely on aspirin use or continuation of aspirin through surgery. CONCLUSIONS: No difference in complication rate of partial nephrectomy was determined to be solely due to prior use of anticoagulation or aspirin use alone with appropriate cessation of anticoagulation preoperatively. Overall, patients on anticoagulation are not at a higher risk of intraoperative or postoperative bleeding complications when undergoing partial nephrectomy.

Antiplatelet De-Escalation Strategies in Patients Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy-the combination of aspirin and a P2Y12 inhibitor-remains the standard antiplatelet regimen recommended to prevent ischemic complications immediately after percutaneous coronary intervention. Nonetheless, recent advances in stent technologies, percutaneous coronary intervention techniques, adjunctive pharmacotherapy for secondary prevention, and the rising awareness of the prognostic impact of bleeding, which are inevitably associated with dual antiplatelet therapy, led to the investigation of alternative antiplatelet regimens related to fewer bleeding and a preserved ischemic protection. Thrombotic complications occur mostly in the first months after percutaneous coronary intervention, while the risk of bleeding remains stable over time; this observation laid the foundation of the concept of antiplatelet de-escalation, consisting of a more intense antiplatelet regimen early after percutaneous coronary intervention, followed by a less potent antiplatelet therapy thereafter. According to new definitions proposed by the Academic Research Consortium, de-escalation can be achieved by discontinuation of 1 antiplatelet agent, switching from a potent P2Y12 inhibitor to clopidogrel, or by reducing the dose of antiplatelet agents. This review discusses the rationale and the evidence supporting antiplatelet de-escalation, provides practical guidance to use these new regimens, and gives insights into future developments in the field.

The Role of Cilostazol, a Phosphodiesterase-3 Inhibitor, in the Development of Atherosclerosis and Vascular Biology: A Review with Meta-Analysis.

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading global cause of mortality. Addressing this vital and pervasive condition requires a multifaceted approach, in which antiplatelet intervention plays a pivotal role, together with antihypertensive, antidiabetic, and lipid-lowering therapies. Among the antiplatelet agents available currently, cilostazol, a phosphodiesterase-3 inhibitor, offers a spectrum of pharmacological effects. These encompass vasodilation, the impediment of platelet activation and aggregation, thrombosis inhibition, limb blood flow augmentation, lipid profile enhancement through triglyceride reduction and high-density lipoprotein cholesterol elevation, and the suppression of vascular smooth muscle cell proliferation. However, the role of cilostazol has not been clearly documented in many guidelines for ASCVD. We comprehensively reviewed the cardiovascular effects of cilostazol within randomized clinical trials that compared it to control or active agents and involved individuals with previous coronary artery disease or stroke, as well as those with no previous history of such conditions. Our approach demonstrated that the administration of cilostazol effectively reduced adverse cardiovascular events, although there was less evidence regarding its impact on myocardial infarction. Most studies have consistently reported its favorable effects in reducing intermittent claudication and enhancing ambulatory capacity in patients with peripheral arterial disease. Furthermore, cilostazol has shown promise in mitigating restenosis following coronary stent implantation in patients with acute coronary syndrome. While research from more diverse regions is still needed, our findings shed light on the broader implications of cilostazol in the context of atherosclerosis and vascular biology, particularly for individuals at high risk of ASCVD.

International Digestive Endoscopy Network consensus on the management of antithrombotic agents in patients undergoing gastrointestinal endoscopy.

Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19.

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR). Five recommendations had the LOE upgraded to A and 2 new recommendations on antithrombotic treatment for patients with COVID-19 were added. Furthermore, a section was added to answer questions about COVID-19 vaccination and vaccine-induced immune thrombotic thrombocytopenia (VITT), for which studies have provided some evidence. We only included recommendations with LOE A or B. Panelists agreed on 19 recommendations, 4 for nonhospitalized, 5 for noncritically ill hospitalized, 3 for critically ill hospitalized, and 2 for postdischarge patients, as well as 5 for vaccination and VITT. A strong recommendation (COR 1) was given for (a) use of prophylactic dose of low-molecular-weight heparin or unfractionated heparin in noncritically ill patients hospitalized for COVID-19, (b) for select patients in this group, use of therapeutic-dose low-molecular-weight heparin/unfractionated heparin in preference to prophylactic dose, and (c) for use of antiplatelet factor 4 enzyme immunoassays for diagnosing VITT. A strong recommendation was given against (COR 3) the addition of an antiplatelet agent in hospitalized, noncritically ill patients. These international guidelines provide recommendations for countries with diverse healthcare resources and COVID-19 vaccine availability.

Baseline Stroke Risk and Efficacy of Dual-Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial.

BACKGROUND: High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy [DAPT]) for transient ischemic attack and minor ischemic stroke. METHODS: We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA2DS2-VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups. RESULTS: A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA2DS2-VASc score (P=0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 [95% CI, 1.44-2.35]; P<0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 [95% CI, 0.90-3.57]; P=0.10). The relative risk reduction with DAPT was similar across SPI-II strata (Pinteraction=0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum. CONCLUSIONS: Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00991029.

Impact of prior use of antiplatelets on COVID-19 susceptibility, progression, and severity: a population-based study.

INTRODUCTION AND OBJECTIVES: Hypercoagulability and thromboembolism are processes that arise from severe acute respiratory syndrome coronavirus 2 infection and are responsible for a high degree of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study sought to assess the effect of antiplatelet drugs on COVID-19 severity (risk of hospitalization and mortality), susceptibility to severe acute respiratory syndrome coronavirus 2 infection, and progression to severe COVID-19. METHODS: We conducted a population-based case-control study in a northwestern region of Spain in 2020. The study involved 3060 participants with a positive polymerase chain reaction test who were hospitalized, 26 757 participants with a positive polymerase chain reaction test who were not hospitalized, and 56 785 healthy controls. RESULTS: Triflusal seemed to be associated with a significant increase in risk of hospitalization (aOR, 1.97; 95%CI, 1.27-3.04) and susceptibility to infection (OR, 1.45; 95%CI, 1.07-1.96). It also appeared to lead to a nonsignificant increase in the risk of mortality (OR, 2.23; 95%CI, 0.89-5.55) and/or progression to more severe disease stages (OR, 1.42; 95%CI, 0.8-2.51). Aspirin seemed to be associated with a statistically significant decrease in susceptibility to severe acute respiratory syndrome coronavirus 2 infection (OR, 0.92; 95%CI, 0.86-0.98). CONCLUSIONS: Triflusal use appears to increase the risk of susceptibility to COVID-19 infection and an even higher risk of hospitalization, whereas the other antiplatelets could be associated with a reduction in the risk of the various outcomes or have no effect on risk. These findings could support reconsideration of triflusal prescription in COVID-19 pandemic situations.

Effects of antiplatelet therapy on menstrual blood loss in reproductive-aged women: a systematic review.

Background: The effects of antiplatelet therapy on menstrual bleeding have not been well characterized. Objectives: To systematically review the effects of antiplatelet therapy on menstrual bleeding. Methods: A literature search was performed for studies of reproductive-aged women who received antiplatelet therapy. Characteristics of menstrual bleeding both before and after initiation of antiplatelet therapy and from comparison groups were collected. Two reviewers independently assessed the risk of bias in individual studies. Results: Thirteen studies with a total of 611 women who received antiplatelet therapy were included. Types of antiplatelet drugs used were aspirin (n = 8), aspirin and/or clopidogrel (n = 2), prasugrel (n = 1), and not specified (n = 2). Risk of bias was assessed at moderate (n = 1), serious (n = 8), critical (n = 2), and no information (n = 2). Three studies reported changes in menstrual blood loss volume. One of these showed no increase during antiplatelet therapy; the other 2 studies suggested that aspirin may increase menstrual blood loss volume. In 3 studies that assessed the duration of menstrual bleeding, up to 13% of women reported an increased duration of menstruation. In 5 studies that reported the intensity of menstrual flow, 13% to 38% of women experienced an increase in the intensity of flow. Five studies reported the prevalence of heavy menstrual bleeding in women who received antiplatelet therapy, with estimates ranging from 7% to 38%. Conclusion: There is lack of high-quality data on the effects of antiplatelet therapy on menstrual bleeding. Aspirin may increase menstrual blood loss, at least in a minority of women, whereas the effects of P2Y12 inhibitors are unknown.

Dual-Pathway Inhibition with Rivaroxaban and Low-Dose Aspirin Does Not Alter Immune Cell Responsiveness and Distribution in Patients with Coronary Artery Disease.

INTRODUCTION: Cardiovascular diseases (CVD) are the leading cause of death globally. Inflammation is an important driver of CVD where tissue damage may lead to the formation of deadly thrombi. Therefore, antithrombotic drugs, such as platelet inhibitors, are crucial for secondary risk prevention in coronary artery disease (CAD) and peripheral artery disease (PAD). For severe forms of the disease, dual-pathway inhibition (DPI) where low-dose aspirin is combined with rivaroxaban has shown improved efficacy in reducing cardiovascular mortality. METHODS: Given this greater improvement in mortality, and the importance of inflammation in driving atherosclerosis, the potential for off-target inflammation-lowering effects of these drugs was evaluated by looking at the change in immune cell distribution and responsiveness to ex vivo lipopolysaccharide (LPS) stimulation after 3 months of DPI in patients with CAD. RESULTS: We observed no changes in whole blood or peripheral blood mononuclear cell (PBMC) immune cell responsiveness to LPS after 3 months of DPI. Additionally, we did not observe any changes in the distribution of total white blood cells, monocytes, neutrophils, lymphocytes, or platelets during the study course. Signs of systemic inflammation were studied using Olink proteomics in 33 patients with PAD after 3 months of DPI. No changes were observed in any of the inflammatory proteins measured after the treatment period, suggesting that the state of chronic inflammation was not altered in these subjects. CONCLUSION: Three months of DPI does not result in any meaningful change in immune cell responsiveness and distribution in patients with CAD or PAD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05210725.

Cilostazol versus Aspirin or Clopidogrel for Reducing Post-Stroke Aspiration Pneumonia: A Nationwide Retrospective Cohort Study.

INTRODUCTION: The association between the use of cilostazol as a post-stroke antiplatelet medication and a reduction in post-stroke pneumonia has been suggested. However, whether cilostazol has a greater preventive effect against post-stroke aspiration pneumonia (AP) than other antiplatelet medications remains unclear. Thus, this study aimed to evaluate whether cilostazol has a greater preventive effect against post-stroke AP than aspirin or clopidogrel. METHODS: Through the Japanese Diagnosis Procedure Combination database, we identified patients who were hospitalized for ischemic stroke between April 2012 and September 2019. We performed 1:1 propensity score matching between patients who received cilostazol alone at discharge and those who received aspirin or clopidogrel alone at discharge. The primary outcome was the 90-day readmission for post-stroke AP. The occurrence of recurrent ischemic stroke within 90 days was also evaluated. RESULTS: Among the 305,543 eligible patients with ischemic stroke, 65,141 (21%), 104,157 (34%), and 136,245 (45%) received cilostazol, aspirin, and clopidogrel, respectively. Propensity score matching generated 65,125 pairs. The cilostazol group had a higher proportion of 90-day post-stroke readmissions with AP than the aspirin or clopidogrel groups (1.5% vs. 1.2%, p < 0.001). The proportion of patients with recurrent ischemic stroke within 90 days was also higher in the cilostazol group (2.4% vs. 2.2%, p = 0.017). CONCLUSION: The present study suggests that cilostazol may not have a greater effect on preventing post-stroke AP within 90 days than other antiplatelet medications. Nevertheless, further randomized controlled trials with longer follow-up periods are warranted.

Migraña poscierre percutáneo de defectos septales auriculares

La migraña es una enfermedad que se ha visto asociada a defectos septales auriculares y a su cierre percutáneo, estipulándose en la literatura que sería una rara complicación, pero la evidencia al respecto es escasa. Se realizó una revisión narrativa sobre definiciones, epidemiología, fisiopatología y tratamiento de la migraña y de la entidad migraña poscierre percutáneo de defectos del septum auricular, incluyendo trabajos observacionales (retrospectivos, prospectivos), estudios randomizados, reportes de casos, artículos de revisión y metaanálisis existentes en PubMed y Cochrane, para aportar al conocimiento de esta entidad.

Migraine is a disease that has been associated with atrial septal defects and its percutaneous closure, stipulating in the literature that it would be a rare complication, but evidence is scarce. A narrative review was conducted on definitions, epidemiology, pathophysiology and treatment of migraine and the migraine entity after percutaneous closure of atrial septum defects, including observational studies (retrospective, prospective), randomized studies, case reports, review articles and meta-analyses existing in PubMed and Cochrane, to contribute to the knowledge of this entity.

A enxaqueca é uma doença que tem sido associada a defeitos do septo atrial e seu fechamento percutâneo, estipulando na literatura que seria uma complicação rara, mas as evidências são escassas. Foi realizada uma revisão narrativa sobre definições, epidemiologia, fisiopatologia e tratamento da enxaqueca e da entidade migranosa após fechamento percutâneo de defeitos do septo atrial, incluindo estudos observacionais (retrospectivos, prospectivos), estudos randomizados, relatos de caso, artigos de revisão e metanálises existentes no PubMed e Cochrane, para contribuir com o conhecimento dessa entidade.

Patients with metabolic dysfunction-associated steatotic liver disease have preserved in vitro responses to antiplatelet drugs.

Background: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at a risk of developing cardiovascular disease. Antiplatelet therapy not only prevents cardiovascular disease in these patients, but may also lower the risk of progression into advanced stages of fibrosis. However, patients with MASLD-associated cirrhosis often have complex changes in the hemostatic system and have been excluded from randomized trials. Objectives: The aim of this study was to assess the potency of antiplatelet drugs in these patients with MASLD-associated cirrhosis. Methods: We included patients with MASLD-associated cirrhosis (n = 19), patients with type 2 diabetes (DM2) and steatosis (n = 22), patients with steatosis only (n = 15), and healthy controls (n = 20). We measured basal platelet aggregation and activation using light transmission aggregometry and flow cytometry. We subsequently measured platelet aggregation and activation after in vitro addition of aspirin, cangrelor, and ticagrelor and compared the antiplatelet response in patients and healthy controls. Results: Rates of aspirin resistance as measured by light transmission aggregometry were similar between patients with MASLD-associated cirrhosis and healthy controls (21% vs 16%), but were significantly higher in patients with DM2 and steatosis (50% [P = .02] vs controls) and patients with steatosis only (53% [P = .05] vs controls). In patients with DM2 and steatosis, but not with MASLD-associated cirrhosis, the potency of cangrelor was significantly lower than that in healthy controls (P = .028). Conclusion: The in vitro potency of aspirin, cangrelor, and ticagrelor in samples of patients with MASLD-associated cirrhosis is similar to that of healthy controls. In contrast, the potency of commonly used antiplatelet drugs may be altered in patients with DM2 and steatosis and in patients with steatosis only.

Antithrombotic therapy in patients after transcatheter aortic valve implantation: a network meta-analysis.

AIMS: The optimal antithrombotic therapy to balance the risk of thrombosis and bleeding in patients who undergo transcatheter aortic valve implantation (TAVI) is unknown. This systematic review/network meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of different oral anticoagulant and antiplatelet regimens in patients post-TAVI. METHODS AND RESULTS: MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to April 2023. Co-primary outcomes were all-cause death and major bleeding. We conducted Bayesian network meta-analyses to compare all interventions simultaneously. For each outcome, we generated odds ratios (ORs) with 95% credible intervals using a random-effects model with informative priors, and ranked interventions based on mean surface under the cumulative ranking curve. We included 11 RCTs (n = 6415), including one unpublished RCT. Three trials enrolled patients with an indication for an oral anticoagulant (OAC). Overall risk of bias was low or with some concerns. Median age was 81 years. Median follow-up was 6 months. The Combination of OAC plus single antiplatelet therapy (SAPT) increased the risk of all-cause death compared with dual antiplatelet therapy (DAPT) (OR 1.78, 95% credible interval 1.15-2.77). No other comparisons for all-cause death were significantly different. For major bleeding, SAPT reduced the risk compared with DAPT, direct-acting OAC, and OAC + SAPT (OR 0.20-0.40), and DAPT reduced the risk compared with OAC + SAPT. SAPT and DAPT ranked best for all-cause death, while SAPT ranked best for major bleeding. CONCLUSION: In post-TAVI patients, SAPT may provide the optimal balance of reducing thrombotic events while minimizing the risk of bleeding.