High Risk Of Bleeding Research Articles

Proton pump inhibitors and cardiovascular risk: a critical review.

Proton pump inhibitors (PPI) are widely used medications for gastrointestinal disorders. Recent research suggests a potential association between long-term PPI use and increased cardiovascular (CV) risk, creating a complex clinical dilemma. This review critically evaluates the current evidence for this association, considering the limitations of observational studies and the lack of definitive confirmation from randomized controlled trials.This review delves into the reported association between PPIs and adverse CV events, examining proposed mechanisms such as drug interactions, electrolyte imbalances induced by PPIs and their potential impact on cardiac and vascular function. Evidence suggests these mechanisms converge, with varying influence depending on patient populations.Clinicians require a risk-benefit analysis for each patient considering their CV risk profile. Alternative gastrointestinal therapies should be explored for high-bleeding risk patients. Medications with lower cytochrome-P450 interaction potential may be preferable among essential PPI users. Elucidating the specific mechanisms by which PPIs might influence CV health, assessing long-term vascular effects and investigating interactions with newer anticoagulant medications are crucial for future research.

Derivation and Validation of the PRECISE-HBR Score to Predict Bleeding After Percutaneous Coronary Intervention.

Accurate bleeding risk stratification after percutaneous coronary intervention (PCI) is important for treatment individualization. However, there is still an unmet need for a more precise and standardized identification of high bleeding risk patients. We derived and validated a novel bleeding risk score by augmenting the PRECISE-DAPT score with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria. The derivation cohort comprised 29,188 patients undergoing PCI, of whom 1136 (3.9%) had a Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding at 1 year, from four contemporary real-world registries and the XIENCE V USA trial. The PRECISE-DAPT score was refitted with a Fine-Gray model in the derivation cohort and extended with the ARC-HBR criteria. The primary outcome was BARC 3 or 5 bleeding within 1 year. Independent predictors of BARC 3 or 5 bleeding were selected at multivariable analysis (p<0.01). The discrimination of the score was internally assessed with apparent validation and cross-validation. The score was externally validated in 4578 patients from the MASTER DAPT trial and 5970 patients from the STOPDAPT-2 total cohort. The PRECISE-HBR score (age, estimated glomerular filtration rate, hemoglobin, white-blood-cell count, previous bleeding, oral anticoagulation, and ARC-HBR criteria) showed an area under the curve (AUC) for 1-year BARC 3 or 5 bleeding of 0.73 (95% CI, 0.71-0.74) at apparent validation, 0.72 (95% CI, 0.70-0.73) at cross-validation, 0.74 (95% CI, 0.68-0.80) in the MASTER DAPT, and 0.73 (95% CI, 0.66-0.79) in the STOPDAPT-2, with superior discrimination than the PRECISE-DAPT (cross-validation: Δ AUC, 0.01; p=0.02; MASTER DAPT: Δ AUC, 0.05; p=0.004; STOPDAPT-2: Δ AUC, 0.02; p=0.20) and other risk scores. In the derivation cohort, a cut-off of 23 points identified 11,414 patients (39.1%) with a 1-year BARC 3 or 5 bleeding risk ≥4%. An alternative version of the score, including acute myocardial infarction on admission instead of white-blood-cell count, showed similar predictive ability. The PRECISE-HBR score is a contemporary, simple 7-item risk score to predict bleeding after PCI, offering a moderate improvement in discrimination over multiple existing scores. Further evaluation is required to assess its impact on clinical practice.

Polygenic risk, aspirin and primary prevention of coronary artery disease.

Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease versus the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12,031 genotyped participants (5,974 aspirin, 6,057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin versus placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk (adjusted Hazard Ratio [aHR]=1.30 [1.06-1.61], P=0.01) but no significant CAD reduction (aHR=0.84 [0.64-1.09], P=0.19). However, among the highest quintile of polygenic risk (q5, top 20% of the GPSMult distribution), there was a 47% reduction in risk of CAD events with aspirin (aHR=0.53 [0.31-0.90], P=0.02) without increased bleeding risk (aHR=1.05 [0.60-1.82], P=0.88). Interaction between the GPSMult and aspirin was significant for CAD (q5 versus q1, P=0.02) but not bleeding (P=0.80). The balance between net benefit and harm on aspirin in the primary prevention setting shifts favourably in individuals with an elevated genetic predisposition.

Transarterial embolization for anterior cranial fossa dural arteriovenous fistula based on multi-modal three-dimensional imaging

Background: Dural arteriovenous fistula (DAVF) in the anterior cranial fossa (ACF) is known to show a high risk of intracranial hemorrhage. Recently, multi-modal fusion imaging with computed tomography angiography, computed tomography venography, and three-dimensional (3D) rotation angiography have been used preoperatively to ensure anatomical safety. We report on endovascular treatment as a first-line approach for ACFDAVF based on the understanding of vascular anatomy obtained from multi-modal fusion imaging. Methods: All patients with ACF-DAVF treated endovascularly as a first-line approach were included in this study. Analyses took into account complications (particularly visual function), immediate angiographic outcomes, and follow-up findings in consecutive patients with ACF-DAVF treated with interventional treatment based on multi-modal fusion imaging. Results: Five patients with ACF-DAVF underwent six sessions of transarterial embolization (TAE) in our institution. The five male patients (mean age, 74.5 years; range, 60–84 years) were treated with liquid embolic agents (Onyx, four procedures; n-butyl 2-cyanoacrylate, two procedures). No difference was seen between preoperative image evaluation and image evaluation during the endovascular procedure, and in all cases, a microcatheter was navigated into a target artery assumed from preoperative multi-modal imaging, allowing treatment completion in a single procedure. In all cases, the shunt disappeared completely and visual function after procedure was maintained. At the last follow-up, all patients showed a modified Rankin scale score of 0 or 1 with no recurrences. Conclusion: Multi-modal fusion imaging facilitates a 3D understanding of the vascular anatomy, allowing TAE as the first-line treatment for ACF-DAVF.

An aspirin-free strategy for percutaneous coronary intervention in patients with diabetes: a pre-specified subgroup analysis of the STOPDAPT-3 trial.

Safety of aspirin-free strategy immediately after percutaneous coronary intervention (PCI) for cardiovascular events in patients with diabetes was unknown. We conducted the prespecified subgroup analysis on diabetes in the STOPDAPT-3 trial, which randomly compared prasugrel (3.75mg/day) monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The co-primary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) at 1 month. Of 5966 study patients, there were 2715 patients (45.5%) with diabetes. Patients with diabetes more often had chronic coronary syndrome, heart failure or cardiogenic shock, and comorbidities than those without. Patients with diabetes compared to those without had higher incidences of major bleeding and cardiovascular events. Regardless of diabetes, the effect of no-aspirin relative to DAPT was not different for the co-primary bleeding (diabetes: 5.05% versus 5.47%; HR, 0.92; 95%CI, 0.66-1.28 and non-diabetes: 3.99% versus 4.07%; HR, 0.98; 95%CI, 0.69-1.38; P for interaction=0.81) and cardiovascular (diabetes: 5.54% versus 5.15%; HR, 1.08; 95%CI, 0.78-1.49 and non-diabetes: 2.95% versus 2.47%; HR, 1.20; 95%CI, 0.79-1.82; P for interaction=0.70) endpoints. The incidences of subacute definite or probable stent thrombosis and any coronary revascularization were higher in the no-aspirin group than in the DAPT group regardless of diabetes. The effects of an aspirin-free prasugrel monotherapy (3.75mg/day) relative to DAPT for major bleeding and cardiovascular events were not different regardless of diabetes. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.

Predictors of bleeding from esophagus veins in patients with liver cirrhosis

Aim: to identify clinical and laboratory predictors of bleeding from the esophageal veins in patients with liver cirrhosis and evaluate their practical significance. Materials and methods. The study materials were the results of an examination of 50 patients treated in the gastroenterology department for liver cirrhosis and 160 patients in surgical departments hospitalized for bleeding from esophageal varices due to liver cirrhosis. All patients were subjected to a standard set of general clinical examinations, ultrasound examination of the abdominal organs, and videoesophagogastroduodenoscopy. Results. When comparing patients with cirrhosis of the liver with and without bleeding from the veins of the esophagus, a statistically significant difference was revealed between the groups in the gender and age composition, blood bilirubin level, and de Ritis coefficient. At the same time, no differences were found in the etiology and severity of liver cirrhosis, blood protein levels, the diameter of the portal and splenic veins, and the proportion of patients with ascites. Conclusions. The detection of a de Ritis coefficient equal to or exceeding 1.8 in a patient with liver cirrhosis can be considered a predictor of a high risk of bleeding from the esophageal veins (sensitivity of the parameter 60.87%, specificity 93.94%) and can be recommended for identifying those in need of priority measures primary prevention.

Polymer free biolimus coated stents to treat acute ST-elevation myocardial infarction in Asian patients.

Patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment-elevation myocardial infarction (STEMI) have a high thrombotic burden and often have a high bleeding risk (HBR). Asian patients have different patterns of thrombotic and bleeding risk from other populations which may be particularly relevant in the setting of PPCI for STEMI. To assess the safety and efficacy of the polymer free biolimus coated coronary stent (PF-BCS, BioFreedomTM, Biosensors International) in Asian STEMI patients. Patients with acute STEMI who received at least one PF-BCS were invited to participate after their index procedure. Follow-up was performed at 1, 4, and 12 months. The primary endpoint was the rate of target lesion failure (TLF) at 1 year. A performance goal was derived from the biolimus eluting stent arm of the COMFORTABLE AMI study which was the only prior dedicated study of biolimus eluting stents in patients with STEMI. A total of 914 patients with STEMI were enrolled. Mean patient age was 60 ± 13 years, diabetes was present in 23.2% and 43% were active smokers. According to the ARC definition, 12.4% of the patients were HBR. TLF rate was 2.54% [95% CI: 1.52-3.56], p-value for non-inferiority <0.0001, p-value for superiority = 0.0004). The rate of definite/probable stent thrombosis was 0.44% [95% CI: 0.16-1.16]. There was a trend toward more BARC 3 to 5 bleeding in ARC-HBR patients (3.69% vs 1.46%, HR = 2.74, [95% CI: 0.87-8.62], p = 0.07). In Asian patients undergoing PPCI for STEMI and treated with variable durations of DAPT, the use of a PF-BCS was associated with low rates of TLF and stent thrombosis (NCT03609346).

Preoperative Depression is Associated With a Higher Risk of Bleeding in Type a Aortic Dissection Repair: A Population Study of National Inpatient Sample From 2015-2020.

Depression is highly prevalent in patients with aortic diseases. While depression has been shown to predispose patients to adverse outcomes after surgery, its impact on postoperative outcomes in Stanford Type A Aortic Dissection (TAAD) has not been established. This study aimed to conduct a population-based examination of the effect of preoperative depression on in-hospital outcomes after TAAD using the National/Nationwide Inpatient Sample (NIS) database, the largest all-layer database in the US. Patients undergoing TAAD repair were identified in NIS from the last quarter of 2015-2020. Multivariable logistic regressions were used to compare in-hospital outcomes between patients with and without preoperative depression, adjusted for demographics, comorbidities, hospital characteristics, primary payer status, and transfer status. There were 321 (7.50%) patients with depression and 3961 (92.50%) non-depressive patients who underwent TAAD repair. Patients with and without depression had comparable in-hospital mortality (11.84% vs 15.37%, P = 0.35). However, Patients with depression had a higher risk of hemorrhage/hematoma (83.49% vs 76.6%, aOR 1.593, 95 CI 1.161-2.184, P < 0.01) and a higher rate of transfer out (40.81% vs 32.62%, aOR 1.396, 95 CI 1.077-1.81, P = 0.01). All other in-hospital complications, hospital length of stay (LOS), and total hospital charge were comparable between patients with and without depression. Preoperative depression is associated with a higher risk of bleeding after TAAD repair. This may be due to anti-depression treatment, such as Selective Serotonin Reuptake Inhibitors (SSRIs), that can disrupt platelet function and lead to abnormal bleeding. While depression is not associated with other major outcomes, preoperative depression screening, as well as hemostatic monitoring and appropriate blood management in patients with depression may be crucial in preventing bleeding complications in TAAD repair.

Contemporary Use of Drug-Coated Balloons for Coronary Angioplasty: A Comprehensive Review.

The interventional treatment of coronary artery disease (CAD) has undergone significant improvements thanks to technological innovations. Nowadays, percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is the standard of care for the treatment of CAD. Nevertheless, the non-negligible incidence of in-stent restenosis (ISR) and suboptimal results in various anatomical settings has led to the development of drug-coated balloons (DCBs). DCBs are catheter-based balloons whose surface is coated with an anti-proliferative drug (mainly Paclitaxel or Sirolimus) loaded onto the balloon surface with different technologies and dose concentrations. In the beginning, these devices were used for the treatment of ISR showing an excellent efficacy profile in the inhibition of intimal hyperplasia. Subsequently, several studies evaluated their use in other angiographical and clinical contexts such as de novo lesions, small vessel disease, diffuse coronary disease, bifurcation lesions, acute coronary syndromes, high-bleeding risk and diabetic patients. This comprehensive review aims to describe the main DCB platforms on the market, their fields of application with the main supporting studies and their future perspectives.

Efficacy and Safety of Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke: A Systematic Review and Meta-analysis

Introduction: Stroke remains a major cause of morbidity and mortality after cardiac surgery. One factor associated with stroke occurrence is postoperative AF (pAF), which predisposes to the formation of atrial thrombus. As most thrombi form in the left atrial appendage (LAA), there is significant interest in LAA as a potential therapeutic target. While guidelines recommend direct oral anticoagulants (DOACs) as the preferred therapy for stroke prevention in patients with AF and a CHA2DS2-VASc score of ≥2, they cannot be administered to all patients who are poor candidates for long-term oral anticoagulation because of the high risk of bleeding, drug compliance and drug tolerance. There are limited data on the efficacy and safety of LAA occlusion (LAAO) during cardiac surgery for stroke prevention. Methods: A comprehensive and relevant search of randomised controlled trials, cohort and case–control studies was conducted. Outcome measures for ischaemic stroke events, all-cause mortality and pAF were extracted and analysed using a random-effects model. Results: Twelve studies were included and 18,982 subjects were analysed. There were 231 ischaemic stroke events in 9,473 patients who received LAAO compared with 371 ischaemic stroke events in 9,509 patients who did not receive LAAO. Concomitant LAAO showed a significant difference in ischaemic event rate (risk ratio [RR] 0.65; [95% CI: 0.55–0.77]; p&lt;0.00001, I2=0%) and all-cause mortality (RR 0.74; 95% CI [0.57–0.97]; p=0.03; I2=68%). For pAF, there was no difference between the two groups (RR 1.08; 95% CI [0.95–1.22]; p=0.24; I2=72). Conclusion: Concomitant LAAO was more effective in preventing ischaemic stroke events and all-cause mortality, with an overall moderate certainty of evidence. However, pAF rates were similar between LAAO and non-LAAO groups.

Clots and bleeds: the outcomes of percutaneous coronary intervention in hemophilia patients with acute coronary syndrome.

Hemophilia is a disease characterized by a high risk of bleeding. With advances in treatment, life expectancy and aging-associated diseases such as coronary artery disease have increased. Our primary objective is to assess for major adverse outcomes, mortality, and length of hospital stay in individuals with hemophilia presenting for acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI). Our retrospective cohort study analyzed data from the Nationwide Inpatient Sample Database (NIS) for 2018 to investigate the outcomes of ACS management with PCI in adults with and without hemophilia. We used ICD-10 codes to exclude patients with significant comorbidities and identify those with ACS undergoing PCI. Propensity score matching and multivariable logistic regression were employed to account for over 20 baseline characteristics, mitigating confounding factors. The incidence of gastrointestinal bleeding (11.0% vs. 2.8%, p < 0.001), hemorrhagic stroke (10.0% vs. 1.4%, p < 0.001), and retroperitoneal hemorrhage (5.6% vs. 1.4%, p < 0.001) was significantly higher in individuals with hemophilia undergoing PCI compared to those without hemophilia. Additionally, venous thromboembolism (VTE) incidence was notably higher in the hemophilia cohort (6.6% vs. 2.4%, p = 0.027). The hemophilia cohort also experienced a higher mortality rate (7.1% vs. 3.3%, p = 0.037) and longer hospital stays. Patients with hemophilia undergoing PCI are at a significantly greater risk of adverse events, increased mortality, and longer hospital stays than the general population. To mitigate the risk of unfavorable outcomes, it is crucial to ensure adequate replenishment of coagulation factors and establish close collaboration between cardiologists and hematologists.

Long-term Outcome of Patients with Atrial Fibrillation and High Risk of Stroke treated with Oral Anticoagulation or Left Atrial Appendage-Occlusion - A Cardinality Matched Analysis.

Atrial fibrillation (AF) poses a significant risk of stroke. Left atrial appendage occlusion (LAAO) is an alternative for patients with contraindications to oral anticoagulation (OAC) or with high risk of bleeding. This study aims to compare the outcomes of LAAO versus conventional stroke prevention in high-risk AF-patients. This secondary analysis incorporates data from the prospective Swiss-AF and Beat-AF cohorts, and the Zurich LAAO Registry. Cardinality matching was performed to create two comparable cohorts: conventional treatment (92% OAC) and LAAO. The primary endpoint was a composite of stroke, cardiovascular (CV) death, and clinically relevant bleeding. Kaplan-Meier method with competing risk analysis was used. Each group included 468 patients (age 76.4 [70.5, 82.0] years, 33% female). The LAAO group exhibited higher baseline bleeding risk (HAS BLED 2.0 [1.0 to 3.0] versus 3.0 [3.0 to 4.0]; p&lt;0.001). Median follow-up time: 6.0 [4.7 to 7.0] years in conventional treatment group and 4.0 [1.5 to 6.1] in LAAO group. No significant difference in the primary composite endpoint (HR 0.87, 95% CI: 0.72 to 1.06, p=0.18), stroke risk (HR 1.14, 95% CI: 0.66 to 1.97, p=0.64), or CV mortality (HR 1.08, 95% CI: 0.82 to 1.42, p=0.60) was observed between groups. LAAO correlated with a significantly lower risk of clinically relevant bleeding (HR 0.61, 95% CI: 0.47 to 0.80, p&lt;0.001). In this cardinality matched analysis with long-term follow-up, LAAO showed similar stroke and CV death rates but lower clinically relevant bleeding risk compared to conventional therapy in high-risk AF-patients.

A Systematic Review of Safety and Efficacy of Factor XI/XIa Inhibitors in Patients With ESKD on Hemodialysis

IntroductionFactor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing a role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD). MethodsWe systematically searched Embase, MEDLINE, and ClinicalTrials.gov for randomized controlled trials evaluating FXI/XIa inhibitors in patients with ESKD on HD, without restricting inclusion to specific comparators or indications. Interventional treatment arms were pooled, and study results were synthesized by fitting random-effects models, calculating odds ratios (OR) and 95% confidence intervals (CI). ResultsFive phase II studies encompassing 1,270 participants were identified, investigating gruticibart, IONIS-FXIRx, osocimab, or fesomersen in the general HD population and using placebo as a comparator. Four studies were fully published and included in the meta-analysis. Use of FXI/XIa inhibitors was associated with an OR of 0.80 (95% CI, 0.47-1.35) for clinically relevant bleeding, 0.51 (95% CI, 0.21-1.28) for major bleeding, and 0.90 (95% CI, 0.49-1.68) for clinically relevant non-major bleeding. The ORs for thromboembolic events and all-cause mortality were 0.66 (95% CI, 0.28-1.56) and 0.46 (95% CI, 0.15-1.40), respectively. ConclusionCurrently available evidence does not indicate a significantly increased bleeding risk of FXI/XIa inhibitors in patients with ESKD on HD compared to placebo. Their efficacy and their association with all-cause mortality need to be investigated in sufficiently powered, randomized controlled phase III trials.

Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model

Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. VT is initiated by the accumulation of platelets and neutrophils at sites of endothelial cell activation. A role for platelet αIIbβ3 in VT is not established, a task complicated by the increased bleeding risk caused by partial agonists such as tirofiban. Here, we show that m-tirofiban, a modified version of tirofiban, does not agonize αIIbβ3 based on lack of neoepitope expression and the cryo-EM structure of m-tirofiban/full-length αIIbβ3 complex. m-tirofiban abolishes agonist-induced platelet aggregation while preserving clot retraction ex vivo and, unlike tirofiban, it suppresses venous thrombogenesis in a mouse model without increasing bleeding. These findings establish a key role for αIIbβ3 in VT initiation and suggest that m-tirofiban and compounds with a similar structurally-defined mechanism of action merit consideration as potential thromboprophylaxis agents in patients at high risk for VT and hemorrhage.

Safety of edoxaban for delayed bleeding in gastrointestinal endoscopic procedures with a high risk of bleeding.

There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding. This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations. Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays. The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.

One-month DAPT after biodegradable-polymer everolimus-eluting stent implantation in women at high-bleeding risk: Insights from the POEM trial.

We conducted a prespecified subanalysis of the POEM trial to assess the association between sex and clinical outcomes following a short 1-month dual-antiplatelet-therapy (DAPT) period after percutaneous coronary intervention (PCI) with bioresorbable polymer everolimus-eluting stent (BP-EES) among patients at high bleeding risk (HBR). Shortening the DAPT period after PCI is an effective bleeding avoidance strategy with contemporary drug-eluting stents. Whether sex affects the risk of adverse events following PCI is still debated. Patients at HBR undergoing PCI with BP-EES were enrolled and treated with 1-month DAPT. If anticoagulation was needed, study participants received an oral anticoagulant (OAC) in addition to a P2Y12 inhibitor for 1 month, followed by OAC only thereafter. The primary endpoint was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12 months. We report sex-based outcomes of patients included in the POEM study. We enrolled 129 (29.1%) women and 314 (70.9%) men. Women were older, with lower hemoglobin levels, and worse renal function. Accordingly, they had a trend for a greater number of HBR criteria fulfilled and a higher PARIS bleeding score. However, they were not at a significantly higher risk for the primary endpoint (men vs. women: 5.17% vs. 3.94%; HR 1.30; 95% CI: 0.48-3.54, p = 0.61), or any of the hemorrhagic and ischemic secondary endpoints. This prespecified subanalysis of the POEM trial suggests that 1-month DAPT following PCI with BP-EES may be a safe and effective therapeutic strategy for women at HBR.

Transfer RNAs are Linked to Ischemic Stroke and Major Bleeding in Patients with End-Stage Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at very high risk for thromboembolism and bleeding. This study aimed to identify small noncoding RNAs (sncRNAs), specifically microRNAs and transfer-RNA (tRNA)-derived fragments (tRFs), as potential novel biomarkers for predicting thromboembolism and bleeding in this high-risk population. In this sncRNA discovery research, we leveraged the VIVALDI cohort, consisting of 625 ESKD patients on hemodialysis, to conduct two nested case-control studies, each comprising 18 participants. The primary outcomes were ischemic stroke in the first study and major bleeding in the second. Plasma samples were processed using the miND pipeline for RNA-seq analysis to investigate differential expression of microRNAs and tRNA/tRFs between cases and their respective matched controls, with results stringently adjusted for the false discovery rate (FDR). No significant differential expression of microRNAs for either ischemic stroke or major bleeding outcomes was observed in the two nested case-control studies. However, we identified four tRNAs significantly differentially expressed in ischemic stroke cases and seven in major bleeding cases, compared with controls (FDR < 0.1). Coverage plots indicated that specific tRNA fragments (tRFs), rather than full-length tRNAs, were detected, however. Alternative mapping approaches revealed challenges and technical limitations that precluded in-depth differential expression analyses on these specific tRFs. Yet, they also underscored the potential of tRNAs and tRFs as markers for thromboembolism and bleeding. While microRNAs did not show significant differential expression, our study identifies specific tRNAs/tRFs as potential novel biomarkers for ischemic stroke and major bleeding in ESKD patients.

Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants.

The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. Among the 62 eligible patients, 53 (85%) were male (median age, 76years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P<0.01) and continuation of antiplatelet therapy (P=0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. Continuous warfarin therapy is preferred. DOAC withdrawal 1day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.

Comparison of Ultrathin- Versus Thin-Strut Stents in Patients With High Bleeding Risk PCI: Results From the COMPARE 60/80 HBR Trial: An Open-Label, Randomized, Controlled Trial.

No randomized data exist on ultrathin-strut stents in patients at high bleeding risk (HBR) undergoing an abbreviated dual antiplatelet therapy after coronary stenting. The aim of this study was to compare the safety and effectiveness of the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent with the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent in patients at HBR with abbreviated dual antiplatelet therapy after stenting. In the investigator-initiated, randomized, open-label COMPARE 60/80 HBR trial (Comparison of the Supraflex Cruz 60 Micron Stent Strut Versus the Ultimaster Tansei 80 Micron Stent Strut in HBR Percutaneous Coronary Intervention Population), 741 patients at HBR according to the Academic Research Consortium HBR criteria were randomized to receive either the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent or thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. Dual antiplatelet therapy was recommended according to the applicable guidelines and trial data for patients at HBR. The primary outcome was net adverse clinical events, the composite of cardiovascular death, myocardial infarction, target vessel revascularization, stroke, and major bleeding, and was powered for noninferiority with an absolute margin of 4.0% at 1-sided 2.5% alpha. Between September 2020 and August 2022, 371 patients were randomized to the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent and 370 patients to the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent at 11 sites in the Netherlands. At 1 year, the primary outcome was observed in 56 (15.4%) patients in the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent group and 61 (17.1%) in the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent group (risk difference, -1.65%; upper boundary of the 1-sided 95% CI, 3.74; P=0.02 for noninferiority at a 0.025 significance level and P=0.55 for 2-sided superiority at a 0.05 significance level). Among patients at HBR with abbreviated dual antiplatelet therapy post-stenting, the use of an ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent was noninferior compared with the use of a thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04500912.

Dual antiplatelet therapy duration and stent type in patients with high bleeding risk: A systematic review and network meta-analysis

BackgroundIt is uncertain whether the efficacy and safety of dual antiplatelet therapy (DAPT) in patients with high bleeding risk (HBR) vary according to DAPT duration and stent type (e.g., durable polymer drug-eluting stents (DP-DESs), biodegradable polymer DESs (BP-DESs), or polymer-free drug-coated stents (PF-DCSs)). We aimed to study the stent type and DAPT duration appropriate for patients with HBR. MethodsPubMed and EMBASE were searched until October 2023. Randomized controlled trials (RCTs) involving patients with HBR that compared standard DAPT (6-12 months) with DP- or BP-DES versus short DAPT (≤3 months) with DP- or BP-DES or PF-DCS or bare-metal stent (BMS) were identified. The primary efficacy outcome was major adverse cardiovascular events (MACEs), defined as cardiovascular death, myocardial infarction (MI), and stroke. The primary safety outcome was major bleeding. Secondary outcomes included MI and stent thrombosis (ST). We performed a network meta-analysis using a random effects model. ResultsThirteen RCTs with a total of 19,418 patients with HBR were included. Compared to standard DAPT with DP-DES, short DAPT with BMS was associated with a higher risk of MACE and MI. For major bleeding, short DAPT strategies were associated with a lower risk than standard DAPT strategies (e.g. short DAPT with DP-DES versus standard DAPT with DP-DES; HR[95% CI]: 0.48[0.28-0.82]). Interestingly, the use of BP-DES was associated with a higher risk of ST than DP-DES (e.g. standard DAPT with BP-DES versus short DAPT with DP-DES; HR[95% CI]: 2.65[1.03-6.79]). ConclusionsIn patients with HBR who underwent percutaneous coronary intervention, a short DAPT strategy with DP-DES should be used since it offers the best combination of efficacy and safety.