[GDF-15 and the risk of bleeding in patients with stable CAD receiving multicomponent antithrombotic therapy: the results of the prospective REGATA register].

AIM: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy. MATERIALS AND METHODS: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [IQR 9.0; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay. RESULTS: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA (p=0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p=0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p=0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p=0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p=0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation. CONCLUSION: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Validation of a Major and Clinically Relevant Nonmajor Bleeding Phenotyping Algorithm on Electronic Health Records.

PURPOSE: Bleeding is an important health outcome of interest in epidemiological studies. We aimed to develop and validate rule-based algorithms to identify (1) major bleeding and (2) all clinically relevant bleeding (CRB) (composite of major and all clinically relevant nonmajor bleeding) within real-world electronic healthcare data. METHODS: We took a random sample (n = 1630) of inpatient admissions to Singapore public healthcare institutions in 2019 and 2020, stratifying by hospital and year. We included patients of all age groups, sex, and ethnicities. Presence of major bleeding and CRB were ascertained by two annotators through chart review. A total of 630 and 1000 records were used for algorithm development and validation, respectively. We formulated two algorithms: sensitivity- and positive predictive value (PPV)-optimized algorithms. A combination of hemoglobin test patterns and diagnosis codes were used in the final algorithms. RESULTS: During validation, diagnosis codes alone yielded low sensitivities for major bleeding (0.16) and CRB (0.24), although specificities and PPV were high (>0.97). For major bleeding, the sensitivity-optimized algorithm had much higher sensitivity and negative predictive values (NPVs) (sensitivity = 0.94, NPV = 1.00), however false positive rates were also relatively high (specificity = 0.90, PPV = 0.34). PPV-optimized algorithm had improved specificity and PPV (specificity = 0.96, PPV = 0.52), with little reduction in sensitivity and NPV (sensitivity = 0.88, NPV = 0.99). For CRB events, our algorithms had lower sensitivities (0.50-0.56). CONCLUSIONS: The use of diagnosis codes alone misses many genuine major bleeding events. We have developed major bleeding algorithms with high sensitivities, which can ascertain events within populations of interest.

Clinical characteristics and prognostic importance of anticoagulant use in ischemic left ventricular aneurysm: a retrospective cohort study.

There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.

Trajectories of Frailty and Clinical Outcomes in Older Adults With Atrial Fibrillation: Insights From the Shizuoka Kokuho Database.

BACKGROUND: The increasing prevalence of frailty has gained considerable attention due to its profound influence on clinical outcomes. However, our understanding of the progression of frailty and long-term clinical outcomes in older individuals with atrial fibrillation remains scarce. METHODS: Using data from 2012 to 2018 from a comprehensive claims database incorporating primary and hospital care records in Shizuoka, Japan, we selected patients aged ≥65 years with atrial fibrillation who initiated oral anticoagulant therapy. The trajectory of frailty was plotted using Sankey plots, illustrating the annual changes in their frailty according to the electronic frailty index during a 3-year follow-up after oral anticoagulant initiation, along with the incidence of clinical adverse outcomes. For deceased patients, we assessed their frailty status in the year preceding their death. RESULTS: Of 6247 eligible patients (45.1% women; mean age, 79.3±8.0 years) at oral anticoagulant initiation, 7.7% were categorized as fit (electronic frailty index, 0-0.12), 30.1% as mildly frail (>0.12-0.24), 35.4% as moderately frail (>0.24-0.36), and 25.9% as severely frail (>0.36). Over the 3-year follow-up, 10.4% of initially fit patients transitioned to moderately frail or severely frail. Conversely, 12.5% of severely frail patients improved to fit or mildly frail. Death, stroke, and major bleeding occurred in 23.4%, 4.1%, and 2.2% of patients, respectively. Among the mortality cases, 74.8% (N=1183) and 3.5% (N=55) had experienced moderately or severely frail and either a stroke or major bleeding in the year preceding their death, respectively. CONCLUSIONS: In a contemporary era of atrial fibrillation management, a minor fraction of older patients on oral anticoagulants died following a stroke or major bleeding. However, their frailty demonstrated a dynamic trajectory, and a substantial proportion of death was observed after transitioning to a moderately or severely frail state.

When Every Minute Counts: REBOA Before Surgery Is Independently Associated With a 15-Minute Delay in Time to Definitive Hemorrhage Control.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a temporizing hemorrhage control intervention, but its inevitable effect on time to operating room (OR) has not been assessed. The aim of our study is to assess the impact of undergoing REBOA before surgery (RBS) on time to definitive hemorrhage control surgery. METHODS: In this retrospective analysis of 2017-2021 ACS-TQIP database, all adult (≥18 years) patients who underwent emergency hemorrhage control laparotomy (≤4 hours of admission) and received early blood products (≤4 hours) were included, and patients with severe head injury (Head-abbreviated injury score > 2) were excluded. Patients were stratified into those who did (RBS) vs those who did not undergo REBOA before surgery (No-RBS). Primary outcome was time to laparotomy. Secondary outcomes were complications and mortality. Multivariable linear and binary logistic regression analyses were performed to identify the independent associations between RBS and outcomes. RESULTS: A total of 32,683 patients who underwent emergency laparotomy were identified (RBS: 342; No-RBS: 32,341). The mean age was 39 (16) years, 78% were male, mean SBP was 107 (34) mmHg, and the median injury severity score was 21 [14-29]. The median time to emergency hemorrhage control surgery was 50 [32-85] minutes. Overall complication rate was 16% and mortality was 19%. On univariate analysis, RBS group had longer time to surgery (RBS 56 [41-89] vs No-RBS 50 [32-85] minutes, P < 0.001). On multivariable analysis, RBS was independently associated with a longer time to hemorrhage control surgery (ß + 14.5 [95%CI 7.8-21.3], P < 0.001), higher odds of complications (aOR = 1.72, 95%CI = 1.27-2.34, P < 0.001), and mortality (aOR = 3.42, 95%CI = 2.57-4.55, P < 0.001). CONCLUSION: REBOA is independently associated with longer time to OR for hemorrhaging trauma patients with an average delay of 15 minutes. Further research evaluating center-specific REBOA volume and utilization practices, and other pertinent system factors, may help improve both time to REBOA as well as time to definitive hemorrhage control across US trauma centers. LEVEL OF EVIDENCE: III. STUDY TYPE: Epidemiologic.

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear. METHODS AND RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]). CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting.

BACKGROUND: Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents. METHODS: The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model. RESULTS: This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %-5.60 %), and 0.90 % (95 % CI: 0.10 %-10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %-12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %-6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %-1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %-0.11 %). CONCLUSION: This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.

Temporal Changes in Long-Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era.

BACKGROUND: There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era. METHODS AND RESULTS: We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P<0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P=0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P=0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P=0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P=0.63). CONCLUSIONS: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Direct-Acting Oral Anticoagulants and Antiseizure Medications for Atrial Fibrillation and Epilepsy and Risk of Thromboembolic Events.

Importance: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency of and the association between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing (EI) ASMs may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk. Objective: To assess the rates of thromboembolic and major bleeding events in adults with AF and epilepsy dispensed DOACs and EI ASMs vs DOACs with non-EI ASMs. Design, Setting, and Participants: This active-comparator, new-user cohort study included US health care data from the Clinformatics Data Mart database from October 2010 to September 2021 for a nationally representative population of adults with AF and epilepsy. Exposure: Evaluations included episodes of contiguous coadministration of DOACs for AF with EI ASMs (exposed) or non-EI ASMs (referent) for epilepsy. Main Outcomes and Measures: Thromboembolic events (primary outcome) and major bleeding events (secondary outcome) were identified based on a series of validated, diagnosis-based coding algorithms. Data-adaptive, high-dimensional propensity score matching was used to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (AHRs) were estimated using Cox proportional hazards regression models with robust variance estimators to account for clustering within matched pairs. Results: This study included 14 078 episodes (median age, 74 [IQR, 67-81]; 52.4% female) and 14 158 episodes (median age, 74 [IQR, 67-81]; 52.4% female) of incident DOAC and ASM use that met eligibility criteria for assessment of thromboembolic and major bleeding outcomes, respectively. Incidence was 88.5 per 1000 person-years for thromboembolic events and 68.3 per 1000 person-years for bleeding events. Compared with use of non-EI ASMs, use of EI ASMs with DOACs was not associated with a difference in risk of thromboembolic events (AHR, 1.10; 95% CI, 0.82-1.46) but was associated with a reduction in risk of major bleeding events (AHR, 0.63; 95% CI, 0.44-0.89). Conclusions and Relevance: In this cohort study, EI ASMs were not associated with alteration in DOAC efficacy. Further research is needed on the reduction in bleeding risk associated with EI ASMs, as this may suggest that pharmacokinetic interactions are associated with lowering DOAC levels without negating therapeutic effects.

Low Remnant Cholesterol and In-Hospital Bleeding Risk After Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concerning, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS: A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0-29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5-25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12-6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identified patients with the highest risk of bleeding events. CONCLUSIONS: Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

Post-procedural Anticoagulation With Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial.

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

BACKGROUND: Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. OBJECTIVE: To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. DESIGN: Population-based cohort study. SETTING: Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). PARTICIPANTS: 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. MEASUREMENTS: Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. RESULTS: Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). LIMITATION: Nonrandomized treatment selection. CONCLUSION: Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. PRIMARY FUNDING SOURCE: National Institutes of Health.

One-Month Dual Antiplatelet Therapy Reduces Major Bleeding Compared With Longer-Term Treatment Without Excess Stent Thrombosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Dual antiplatelet therapy (DAPT) remains the gold standard in patients who underwent percutaneous coronary intervention (PCI). This meta-analysis aims to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor after PCI with drug-eluting stents (DES). We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central Registry, and ClinicalTrials.gov databases and identified 5 randomized controlled trials with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary end point was major bleeding, and the co-primary end point was stent thrombosis. The secondary end point included all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events. Compared with >1-month DAPT, the 1-month DAPT was associated with a lower rate of major bleeding (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45 to 0.97, p = 0.03, I2 = 71%), whereas stent thrombosis had a similar rate in both study groups (OR 1.08, 95% CI 0.81 to 1.44, p = 0.60, I2 = 0.0%). The study groups had similar risks for all-cause mortality (OR 0.89, 95% CI 0.77 to 1.04, p = 0.14, I2 = 0.0%), cardiovascular death (OR 0.84, 95% CI 0.59 to 1.19, p = 0.32, I2 = 0.0%), myocardial infarction (OR 1.04, 95% CI 0.89 to 1.21, p = 0.62, I2 = 0.0%), and stroke (OR 0.82, 95% CI 0.64 to 1.05, p = 0.11, I2 = 6%). The risk of major adverse cardiovascular or cerebrovascular events was lower (OR 0.86, 95% CI 0.76 to 0.97, p = 0.02, I2 = 25%) in the 1-month DAPT compared with >1-month DAPT. In conclusion, in patients who underwent PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduced major bleeding with no risk of increased thrombotic risk compared with longer-term DAPT.

Direct Oral Anticoagulants and Concomitant Anti-seizure Medications: A Retrospective, Case-Control Study in a Real-World Setting.

PURPOSE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls. METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province. FINDINGS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group. IMPLICATIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

To treat or not to treat: a comparative effectiveness analysis of oral anticoagulant outcomes among U.S. nursing home residents with atrial fibrillation.

BACKGROUND: Nursing home residents with atrial fibrillation are at high risk for ischemic stroke, but most are not treated with anticoagulants. This study compared the effectiveness and safety between oral anticoagulant (OAC) users and non-users. METHODS: We conducted a new-user retrospective cohort study by using Minimum Data Set 3.0 assessments linked with Medicare claims. The participants were Medicare fee-for-service beneficiaries with atrial fibrillation residing in US nursing homes between 2011 and 2016, aged ≥ 65 years. The primary outcomes were occurrence of an ischemic stroke or systemic embolism (effectiveness), occurrence of intracranial or extracranial bleeding (safety) and net clinical outcome (effectiveness or safety outcomes). Secondary outcomes included total mortality and a net clinical and mortality outcome. Cox proportional hazards and Fine and Grey models estimated multivariable adjusted hazard ratios (aHRs) and sub-distribution hazard ratios (sHRs). RESULTS: Outcome rates were low (effectiveness: OAC: 0.86; non-users: 1.73; safety: OAC: 2.26; non-users: 1.75 (per 100 person-years)). OAC use was associated with a lower rate of the effectiveness outcome (sHR: 0.69; 95% Confidence Interval (CI): 0.61-0.77), higher rates of the safety (sHR: 1.70; 95% CI: 1.58-1.84) and net clinical outcomes (sHR: 1.20; 95% CI: 1.13-1.28) lower rate of all-cause mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61), and lower rate of the net clinical and mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61). Warfarin users, but not DOAC users, had a higher rate of the net clinical outcome versus OAC non-users. CONCLUSIONS: Our results support the benefits of treatment with OACs to prevent ischemic strokes and increase longevity, while highlighting the need to weigh apparent benefits against elevated risk for bleeding. Results were consistent with net favorability of DOACs versus warfarin.

Incidence of acute Deep Vein Thrombosis in pediatric and adolescent orthopedic trauma hospitalized patients and effect of rivaroxaban treatment.

OBJECTIVE: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT. METHODS: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months. RESULTS: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000). CONCLUSIONS: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Predictive Value of HAS-BLED and HEMORR2HAGES Bleeding Risk Scores After Percutaneous Coronary Intervention.

BACKGROUND: Various scoring systems have been developed to assess the risk of bleeding in medical settings. HAS-BLED and HEMORR2HAGES risk scores are commonly used to estimate bleeding risk in patients receiving anticoagulation for atrial fibrillation, but data on their predictive value in patients undergoing percutaneous coronary intervention (PCI) are limited. METHODS: This study evaluated and compared the predictive abilities of the HAS-BLED and HEMORR2HAGES bleeding risk scores in all-comer patients undergoing PCI. The PARIS score, specifically designed for patients undergoing PCI, was used as a comparator. The scores were calculated at baseline and compared with the occurrence of events during a 2-year clinical follow-up period. Between 2015 and 2017, all consecutive patients undergoing PCI we re prospectively enrolled and divided into risk tertiles based on bleeding risk scores. The primary end points were hierarchical major bleeding events, defined by Bleeding Academic Research Consortium types 3 through 5, and patient-oriented composite end points according to Bleeding Academic Research Consortium classification, which were assessed during the 2-year follow-up period. RESULTS: A total of 1,080 patients completed the follow-up period. Two years after index, 189 patients (17.5%) had experienced any bleeding, with 48 events (4.4%) classified as Bleeding Academic Research Consortium types 3 to 5. All bleeding risk scores showed statistically significant predictive ability for bleeding events. The HEMORR2HAGES score (C statistic, 0.73) was more effective than the HAS-BLED score (C statistic, 0.66; P = .07) and the PARIS score (C statistic, 0.66; P = .06) in predicting risk of major bleeding. Patients in high-risk bleeding groups also experienced a higher incidence of patient-oriented composite end points. CONCLUSIONS: The HEMORR2HAGES, HAS-BLED, and PARIS risk scores exhibited good predictive abilities for bleeding events following PCI. Patients at high risk of bleeding also demonstrated increased ischemic risk and higher mortality during the 2-year follow-up period.