Rates Of Major Bleeding Research Articles

Abstract 14237: Anticoagulation Strategies After Transcatheter Aortic Valve Implantation in Patients Without an Indication of Oral Anticoagulants, Network Meta Analysis of Randomized Controlled Trials

Introduction. Transcatheter aortic valve implantation (TAVI) is currently the mainstay treatment for aortic valve diseases, yet postoperative anticoagulation strategies after TAVI is still debatable. Thus, we aim to investigate the safety and efficacy of direct oral anticoagulants (DOACs) vs. single-antiplatelet therapy (SAPTs) vs. dual-antiplatelet therapy (DAPT) vs. Vitamin K antagonists (VKAs) in patients undergoing TAVI and without an indication of OACs. Methods: PubMed, Web of Science, Scopus, and Embase were systematically searched up to December 2022. A frequentist network meta-analysis has been conducted using a random-effects model calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: We included 9,087 patients from 11 studies. Compared to DOACs, DAPT, SAPT, and VKAs were associated with significantly lower odds for short-term all-cause mortality (OR: 0.62; 95% CI [0.46-0.86]), (OR: 0.42; 95% CI [0.29-0.60]), (OR:0.54; 95% CI [0.31, 0.94]), respectively. DAPT was also associated with higher short-term major bleeding risk (OR:2.66; 95% CI [1.46-3.86]). Furthermore, both DAPT and SAPT were associated with significantly higher long-term bleeding rates with (OR: 1.78; 95% CI, [1.15-2.41]) and (OR:2.32; 95% CI, [1.29-3.35]), respectively. However, VKAs were associated with lower long-term bleeding rates (OR: 0.61; 95% CI, [0.24-0.98]). No intervention showed a significant difference over DOACs in terms of long-term all-cause mortality, cardiovascular mortality, and stroke, except for DAPT which showed higher odds of long-term all-cause mortality (OR: 1.83; 95% CI, [1.29-2.37]). Conclusion: Despite the long-term higher rates of major bleeding, SAPT was effective in preventing both short and long-term all-cause mortality compared to DAPT, which has both short, long term major bleeding and higher long-term all-cause mortality. Further RCTs are still required to confirm SAPT superiority compared to other strategies.

Abstract 15587: Iimpact of Body Mass Index on Bleeding Events Patients Undergoing Percutaneous Coronary Intervention With or Without High Bleeding Risk

Introduction: High body mass index (BMI) values are associated with a lower risk of ischemic complications after percutaneous coronary intervention (PCI). Hypothesis : Higher BMI values may correlate with fewer bleeding after PCI in patients meeting or not the High Bleeding Risk (HBR) criteria of the Academic Research Consortium (ARC). Methods: All patients undergoing PCI between 2012 and 2019 at the Mount Sinai Hospital were included and stratified in 5 BMI categories according to World Health Organization definition. Patients where considered at HBR if they fulfilled ≥1 major or ≥2 minor ARC-HBR criteria. The primary outcome was major bleeding, the secondary outcome was post-discharge major bleeding at 1 year after PCI. Risks for these outcomes were obtained using a multivariable Cox regression model adjusted for the ARC-HBR criteria. Results: Among 16,229 patients, 20.2% had a BMI ≥18.5-25 (normal), 40.7% had a BMI ≥25-30, 24.4% had a BMI ≥30-35, 9.2% had a BMI ≥35-40, and 4.8% had a BMI ≥40 kg/m 2 . The proportion of patients meeting the ARC-HBR criteria progressively decreased from 48% in the normal BMI group to 41% in the highest BMI group. As compared to the normal BMI group (6.0%), the 1-year risk of major bleeding was significantly lower (p<0.05) in the groups with BMI ≥25-30 (4.1%, adj. HR 0.73, 95% CI 0.60-0.88), with BMI ≥30-35 (3.5%, Adj. HR 0.62, 95% CI 0.49-0.77), with BMI ≥35-40 (4.2%; Adj. HR 0.72, 95% CI 0.54-0.9), while it was similar in the group of BMI ≥40 (4.9%, Adj. HR 0.83, 95% CI 0.58-1.18) ( A ). These differences were driven by lower rates of in-hospital bleeding in patients with BMI ≥25-40 kg/m 2 . Among HBR patients, 1-year rates of major bleeding were consistently above 4% in each BMI category, but relatively lower for BMI ≥25-40 kg/m 2 ( B ). Conclusions: BMI values between 25 and 40 kg/m 2 were associated with an attenuated risk of major bleeding at 1-year in patients undergoing PCI and this association was consistent among HBR individuals.

Short duration of dual antiplatelet therapy following complex percutaneous coronary intervention: A systematic review and meta-analysis

Introduction and aimThe optimal composition and duration of antiplatelet therapy after complex percutaneous coronary intervention (PCI) remains unclear. We conducted a meta-analysis to compare 1–3 months of dual antiplatelet therapy (DAPT) followed by monotherapy vs. 12 months of DAPT. MethodMEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were queried for studies comparing 1–3 months of DAPT followed by monotherapy vs. 12 months of DAPT in the outcomes of complex PCI from inception through January 2023. Outcomes of interest included major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, target vessel revascularization, and stroke. ResultsCompared to 12 months, 1–3 months of dual antiplatelet therapy had a weak association with less major bleeding (OR 0.67; 95 % CI, 0.44–1.00; p = 0.05; I2 = 28 %). There were no significant differences between the shorter and longer antiplatelet therapy in terms of all-cause mortality (OR 0.83; 95 % CI, 0.59–1.16; p = 0.21; I2 = 17 %), cardiovascular mortality (OR 0.87; 95 % CI, 0.53–0.42; p = 0.50; I2 = 0), MI (OR 0.97; 95 % CI, 0.69–1.35; p = 0.82; I2 = 32 %), stent thrombosis (OR 1.17, 95 % CI, 0.77–1.76; p = 0.38; I2 = 0 %), target vessel revascularization (OR 1.05, 95 % CI, 0.58–1.89; p = 0.82; I2 = 64 %), or stroke (OR 1.10, 95 % CI, 0.55–2.17; p = 0.37; I2 = 7 %);. ConclusionAmong patients undergoing complex PCI, DAPT for 1–3 months may be associated with less major bleeding but similar rates of cardiovascular events (death, MI, stroke, stent thrombosis, and revascularization) compared to DAPT for 12 months.

Efficacy and safety of direct oral anticoagulants in splanchnic vein thrombosis: a pooled analysis of literature studies

BackgroundLimited evidence is available on management of splanchnic vein thrombosis (SVT). ObjectivesThis study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment. MethodsStudies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders. ResultsWe included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I2 = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I2 = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I2 = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I2 = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I2 = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality. ConclusionThe results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.

Atrial Fibrillation Patients with Immune Thrombocytopenia: A Review of Management Options and Bleeding Risks

Aim : The objective of this research is to review the bleeding risks in patients with atrial fibrillation (Afib) and immune thrombocytopenia (ITP) and explore various management strategies to formulate an optimal therapeutic approach that improves the prognosis of these patients. Methods: In this study, we devised our search approach by utilizing PubMed's Medical Subject Headings (MeSH) terms and incorporating pertinent keywords extracted from article titles and abstracts. To ensure a comprehensive scope, we integrated terms associated with immune thrombocytopenia purpura, such as “Immune Thrombocytopenia,” and similar expressions. Additionally, terms related to atrial fibrillation, including “atrial fibrillation,” were included to identify articles discussing atrial fibrillation in the context of immune thrombocytopenia. To adapt the initial search strategy for Embase, Web of Science, and Scopus databases, we employed a polyglot translator. All identified studies resulting from the search strategy were imported into EndNote, where duplicate articles were meticulously removed. The remaining studies were then transferred to Rayyan for further duplicate elimination and to initiate the screening process. The study incorporates full-text articles, submitted abstracts, and conference abstracts. Excluded from this analysis were studies falling into the following categories: (1) animal studies, (2) reviews or non-original articles, and (3) non-English articles. Results: A total of 1891 articles were retrieved from four databases, and after careful selection, 14 relevant full-text articles were analyzed. Among these, 12 studies investigated the efficacy of anticoagulants in managing cases of concurrent Afib and ITP as well as their bleeding risks. Comparing bleeding risk between groups was usually done through measuring by CHA 2DS 2 VASc or HAS BLED scoring systems and survival was also compared by using Kaplan-Meier curves A few of them also compared the efficacy and safety of warfarin against Non-Vitamin K Antagonists which has shown that Non-Vitamin K Antagonists have a lower event rate of major bleeding, lower hazard ration of systemic embolism and higher survival rate compared to warfarin The remaining two papers explored the efficacy and safety of surgical interventions, specifically left atrial appendage closure. Many studies reported that anticoagulant therapies were associated with reduced bleeding risk and have shown promising outcomes in managing patients with Afib and ITP. Additionally, percutaneous left atrial appendage closure has been reported to be a potentially safe management option for atrial fibrillation in patients with primary hemostatic disorders, including thrombocytopenia. Conclusion: In essence, this review focused on investigating the bleeding risk associated with atrial fibrillation (Afib) in patients with immune thrombocytopenia (ITP) and examining available management strategies. While the precise pathophysiological mechanisms linking atrial fibrillation and ITP remain incompletely understood, the review emphasized the intricate interplay between thromboembolic risk and bleeding complications in this specific patient group. The findings suggest that certain anticoagulation regimens and also left atrial appendage closure have shown promising safety and effectiveness in Afib patients with thrombocytopenia. Nevertheless, further research with larger sample sizes and diverse populations is needed to enhance our understanding of the Afib-ITP relationship. Such studies will yield more definitive conclusions and valuable insights into optimal anticoagulation approaches and alternative therapies for patients with both Afib and ITP.

Comparison of Khorana Vs. Onkotev Predictive Score to Individualize Anticoagulant Prophylaxis in Ambulatory Patients with Cancer

Background: The current guidelines [ J Clin Oncol. 2020;38(5):496] recommend using the risk assessment model (RAM) Khorana score ≥2 [ Blood. 2008;111(10):4902-4907] for primary anticoagulant prophylaxis (PP) of venous thromboembolism (VTE) in patients treated for cancer in an outpatient setting. Recently, a novel RAM, the ONKOTEV score [ JAMA Network Open 2023;6(2):e230010] has been prospectively externally validated with good predictive performance. Like all other established RAMs, the Khorana Score and ONKOTEV models aim to assess the incidence of VTE accurately but do not integrate the expected benefits and potential harms of treatment to determine the clinical utility of the competing management alternatives. We set out to compare the clinical utility of the Khorana Score vs. the ONKOTEV predictive model to guide the PP of VTE in patients receiving anticancer treatment. Methods: We used the ONKOTEV validation dataset (n=425). The ONKOTEV score included the Khorana Score (dichotomized as Khorana score &amp;gt;2 vs. ≤ 2) and three readily available clinical information (also dichotomized): history of previous VTE, the presence of metastatic disease, and clinical or radiological assessment of vascular or lymphatic compression by tumor. After assessing the models' performance (discrimination, calibration), we applied a generalized decision curve analysis (gDCA) to integrate the effects of treatments with the models' predictive accuracy. This, in turn, allowed us to develop individualized recommendations for using PP for VTE in patients receiving anticancer treatment. We calculated net benefits (NB) to compare three management strategies: don't provide any treatment vs. administer prophylaxis to all patients receiving anticancer treatment for VTE vs. use the Khorana or ONKOTEV model to guide PP of VTE. According to gDCA, the best treatment is the one with the highest NB. We obtained data on treatment effects from the meta-analysis of published randomized trials comparing direct oral anticoagulants (DOAC) and low-molecular-weight heparins (LMWH) vs. placebo [ Annals of Palliative Medicine. 2020;9(5):2970]. We estimated that DOAC reduced the risk of VTE by 57% [relative risk reduction (RRR) =0.57 (95%CI: 0.13 to 0.79)] and LMWH by 48% [RRR=0.48 (95%CI: 0.42 to 0.66)]. We assessed the major bleeding rate on DOAC as 0.01 (95%CI: 0.006 to 0.04) and 0.02 (95%CI: 0.01 to 0.03) for LMWH. Results: Both RAMs had a satisfactory performance. Harell's C discrimination statistics was 0.71 for ONKOTEV and 0.66 for Khorana Score with good calibration properties (with intercept and the slope not statistically significantly different from 0 and 1, respectively). Fig 1A shows the results based on the default assumptions: if the patient values avoiding the morbidity of VTE 1.6 to 5 times more (0.2&amp;lt;RV&amp;lt;0.6) than the major bleeding, then offering DOAC to all patients receiving PP for VTE represents the most optimal management strategy. When the patients would rather avoid the consequences of the major bleeding by &amp;gt;2.5x more than the morbidity of VTE, using the ONKOTEV model to guide the administration of DOAC represents the best treatment strategy. If we assume that RRR ≤ 0.2, relying on the ONKOTEV model to guide the use of DOAC becomes the most optimal approach to PP of VTE in patients receiving anticancer treatment (Fig 1B). Conclusion: ONKOTEV model is superior to Khorana Score in guiding individualized PP for VTE in ambulatory patients with cancer. It is particularly helpful when the patient values avoiding major bleeding more than the morbidity of VTE. Our analysis provides new recommendations for PP of VTE receiving outpatient treatment for cancer, calling for updating the current guidelines for PP of VTE in this setting.

Intra-Cardiac versus Transesophageal Echocardiographic Guidance for Left Atrial Appendage Occlusion with a Watchman FLX Device.

This study aimed to compare the peri-procedural success and complication rate within a large registry of intra-cardiac echocardiography (ICE)- vs. transesophageal echocardiography (TEE)-guided left atrial appendage occlusion (LAAO) procedures with a Watchmann FLX device. Data from 772 LAAO procedures, performed at 26 Italian centers, were reviewed. Technical success was considered as the final implant of a Watchmann FLX device in LAA; the absence of pericardial tamponade, peri-procedural stroke and/or systemic embolism, major bleeding and device embolization during the procedure was defined as a procedural success. One-year stroke and major bleeding rates were evaluated as outcome. ICE-guided LAA occlusion was performed in 149 patients, while TEE was used in 623 patients. Baseline characteristics were similar between the ICE and TEE groups. The technical success was 100% in both groups. Procedural success was also extremely high (98.5%), and was comparable between ICE (98.7%) and TEE (98.5%). ICE was associated with a slightly longer procedural time (73 ± 31 vs. 61.9 ± 36 min, p = 0.042) and shorter hospital stay (5.3 ± 4 vs. 5.8 ± 6 days, p = 0.028) compared to the TEE group. At one year, stroke and major bleeding rates did not differ between the ICE and TEE groups. A Watchmann FLX device showed high technical and procedural success rate, and ICE guidance does not appear inferior to TEE.

Bivalirudin versus unfractionated heparin in patients with myocardial infarction undergoing percutaneous coronary intervention: A systematic review and meta-analysis of randomized controlled trials

BackgroundBivalirudin is an alternative accepted therapy to unfractionated heparin for patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). We aimed in this meta-analysis to compare bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. MethodsWe have screened PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (inception through January 8th, 2023) for randomized controlled trials (RCTs) evaluating bivalirudin versus unfractionated heparin in patients with MI undergoing PCI. The DerSimonian and Laird method was used for estimation of tau2 to calculate the risk ratio (RR) and 95 % confidence interval (CI). ResultsTen RCTs with a total of 40,069 participants were included in our analysis. Bivalirudin as compared with unfractionated heparin was associated with significant decrease in major bleeding (RR 0.64 [0.52 to 0.79]; p < 0.01; I2 = 69 %) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.01; I2 = 0 %). There was no significant difference between bivalirudin and unfractionated heparin groups in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.14]; p = 0.73; I2 = 52 %), all-cause mortality (RR 0.89 [0.77 to 1.04]; p = 0.15; I2 = 23 %), MI (RR 1.02 [0.87 to 1.19]; p = 0.80; I2 = 36 %), stent thrombosis (RR 1.12 [0.52 to 2.40]; p = 0.77; I2 = 82 %), or stroke (RR 0.97 [0.73 to 1.29]; p = 0.85; I2 = 0 %). ConclusionOur meta-analysis suggests that bivalirudin compared with unfractionated heparin in patients with MI undergoing PCI was associated with lower rates of major bleeding and cardiovascular mortality without a significant difference in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis.

Absorbable Clips Applied in Thoracoscopic Anatomical Lung Resection in Younger Children.

This study aims to evaluate the feasibility and safety of a 5-mm absorbable clips applied in thoracoscopic anatomical lung resection in younger children. Demographic data and intra- and postoperative parameters of the two groups (Abs-o-lock® group and Hem-o-lok® group) were reviewed. In the Abs-o-lock® group, 5-mm absorbable clips were used in thoracoscopic anatomical lung resection on all patients from January 2020 to March 2021. In the Hem-o-lok® group, 5-mm Hem-o-lok® clips were used from January to December 2019. The primary outcomes were the one-time success rate of ligation, major bleeding rate, intraoperative dislodgement rate and operative time, which were compared between the two groups. There were 224 patients involved in this study, of whom 103 were in the Abs-o-lock® group and 121 were in the Hem-o-lok® group. The one-time success rate of ligation was 96.5% in the Abs-o-lock® group and 98.9% in the Hem-o-lok® group (p < 0.05). No major bleeding occurred in either group. The intraoperative dislodgement rate did not significantly differ between the two groups (p = 1.0). The operative time consumed in the Abs-o-lock® group was much longer than that in the Hem-o-lok® group for subgroups of resection of extralobar sequestration (p < 0.05), lobectomy (p < 0.05) and segmentectomy (p < 0.05). Compared to Hem-o-lok® clips, it is feasible and safe to apply 5-mm absorbable clips for vessel sealing during thoracoscopic anatomical lung resection in younger children.

Coagulation-monitored, dose-adjusted catheter-directed thrombolysis or pharmaco-mechanical thrombus removal in deep vein thrombosis.

Background: Pharmaco-mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are therapeutic options for selected patients with acute deep vein thrombosis (DVT) to prevent post-thrombotic syndrome (PTS). Patients and methods: We aimed to describe the clinical characteristics and outcomes of 159 patients with symptomatic iliofemoral DVT undergoing PMT alone, CDT alone, or CDT followed by PMT (bail-out) in the Swiss Venous Stent Registry. The primary outcome was the incidence of peri-interventional major and minor bleeding complications (ISTH criteria). Secondary outcomes included the incidence of PTS and stent patency after 3 years. Results: Mean age was 49±20 years and 58% were women. DVT involved the iliac veins in 99% of patients, whereas 53% had an underlying iliac vein compression. PMT alone was used in 40 patients, CDT alone in 77, and 42 received initial CDT followed by bail-out PMT due to insufficient thrombus clearance. Single-session PMT was the preferred approach in patients with iliac vein compression, patent popliteal vein, and absence of IVC thrombus. Patients treated with PMT alone received a lower r-tPA dose (median 10 mg, IQR 10-10) vs. those treated with CDT (20 mg, IQR 10-30). The rate of peri-interventional major bleeding was 0%, 1%, and 2%, whereas that of minor bleeding was 0%, 1%, and 12%, respectively, all occurring during CDT. After 3 years, PTS occurred in 6%, 9%, and 7% of patients, respectively. The primary stent patency rate was 95%, 88%, and 83%, respectively. Conclusions: The use of PMT and CDT for iliofemoral DVT was overall safe and resulted in high long-term patency and treatment success. Given the less severe presentation of DVT, single-session PMT appeared to be characterized by numerically better primary patency and lower perioperative bleeding event rates than CDT.

Safety and Effectiveness of Apixaban Versus Warfarin in Japanese Patients with Nonvalvular Atrial Fibrillation Stratified by Renal Function: A Retrospective Cohort Study.

We previously conducted a retrospective cohort study using chart review of oral anticoagulant-naïve Japanese patients with nonvalvular atrial fibrillation (NVAF) that assessed the risk of major bleeding and stroke/systemic embolism (SE) events of apixaban versus warfarin. In this subgroup analysis, we compared the risk of major bleeding and stroke/SE events by stratifying patients into four subgroups matched 1:1 using propensity score matching (PSM) according to baseline creatinine clearance (CrCl; mL/min): ≥15 to <30, ≥30 to <50, ≥50 to <80, and ≥80. Of the 7074 patients in the apixaban group and 4998 in the warfarin group eligible for inclusion in the analysis, 4385 were included in each group after PSM. Incidence rates of major bleeding and stroke/SE events were generally lower with apixaban versus warfarin across the CrCl subgroups. When all patients with a CrCl change of <0 mL/min per year during the study period (apixaban, n=3871; warfarin, n=2635) were stratified into four subgroups based on the magnitude of CrCl decline (median CrCl change [mL/min] per year: -1.09, -3.48, -7.54, and -36.92 for apixaban, and -1.10, -3.65, -7.85, and -40.40 for warfarin), the incidence rates of major bleeding and stroke/SE events generally increased with an increasing CrCl decline per year in both groups. In Japanese patients with NVAF, the safety and effectiveness of apixaban and warfarin were consistent across different renal subgroups, including those with severe renal impairment. Our results highlight the importance of monitoring renal function variations over time in patients with NVAF. NCT03765242.

Evaluation of Lead-In Direct Oral Anticoagulant Prescribing Practices in Newly Diagnosed Venous Thromboembolism.

Various lead-in dosing strategies have been used in clinical practice for venous thromboembolism (VTE), and guidelines do not currently address if the full lead-in dosing duration is necessary after receiving parenteral anticoagulation. This study aims to identify whether full lead-in dosing duration surrounding parenteral anticoagulation affects thrombotic and bleeding outcomes. A single-center, retrospective cohort study was conducted of hospitalized patients diagnosed with VTE and treated with apixaban or rivaroxaban. Patients were grouped depending on duration of lead-in dosing, with the full lead-in dosing group considered as the appropriate duration of the direct oral anticoagulant. The primary outcome was the recurrence of VTE within the index admission to 6months. Secondary outcomes included major bleeding, clinically relevant minor bleeding, and mortality.Ninety-three patients were prescribed full lead-in dosing, while 99 patients received reduced lead-in dosing. The primary outcome of recurrent VTE was similar between the reduced lead-in group compared to the full lead-in group (3% vs 2%; P=1.0). Major bleeding within the index admission was significantly higher in the reduced lead-in group: 11 versus 2 (P=.02). There were no significant differences in other secondary outcomes. Full lead-in dosing compared to reduced lead-in dosing duration for VTE had similar rates of thrombotic and mortality events. The higher rate of major bleeding in the reduced lead-in dosing group likely reflects the prescribing practices in less stable patients. This study provides evidence to support reduced lead-in dosing duration in high-risk patients without compromising efficacy outcomes.

Comparative Safety and Effectiveness of Warfarin or Rivaroxaban Versus Apixaban in Patients With Advanced CKD and Atrial Fibrillation: Nationwide US Cohort Study

Head-to-head data comparing the effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are lacking. We compared the safety and effectiveness of warfarin or rivaroxaban versus apixaban in patients with AF and non-dialysis-dependent CKD stage 4/5. Propensity score-matched cohort study. 2 nationwide US claims databases, Medicare and Optum's deidentified Clinformatics Data Mart Database, were searched for the interval from January 1, 2013, through March 31, 2022, for patients with nonvalvular AF and CKD stage 4/5 who initiated warfarin versus apixaban (matched cohort, n=12,488) and rivaroxaban versus apixaban (matched cohort, n= 5,720). Warfarin, rivaroxaban, or apixaban. Primary outcomes included major bleeding and ischemic stroke. Secondary outcomes included all-cause mortality, major gastrointestinal bleeding, and intracranial bleeding. Cox regression was used to estimate HRs, and 1:1 propensity-score matching was used to adjust for 80 potential confounders. Compared with apixaban, warfarin initiation was associated with a higher rate of major bleeding (HR, 1.85; 95% CI, 1.59-2.15), including major gastrointestinal bleeding (1.86; 1.53-2.25) and intracranial bleeding (2.15; 1.42-3.25). Compared with apixaban, rivaroxaban was also associated with a higher rate of major bleeding (1.69; 1.33-2.15). All-cause mortality was similar for warfarin (1.08; 0.98-1.18) and rivaroxaban (0.94; 0.81-1.10) versus apixaban. Furthermore, no statistically significant differences for ischemic stroke were observed for warfarin (1.14; 0.83-1.57) or rivaroxaban (0.71; 0.40-1.24) versus apixaban, but the CIs were wide. Similar results were observed for warfarin versus apixaban in the positive control cohort of patients with CKD stage 3, consistent with randomized trial findings. Few ischemic stroke events, potential residual confounding. In patients with AF and advanced CKD, rivaroxaban and warfarin were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population. Different anticoagulants have been shown to reduce the risk of stroke in patients with atrial fibrillation, such as warfarin and direct oral anticoagulants like apixaban and rivaroxaban. Unfortunately, the large-scale randomized trials that compared direct anticoagulants versus warfarin excluded patients with advanced chronic kidney disease. Therefore, the comparative safety and effectiveness of warfarin, apixaban, and rivaroxaban are uncertain in this population. In this study, we used administrative claims data from the United States to answer this question. We found that warfarin and rivaroxaban were associated with increased risks of major bleeding compared with apixaban. There were few stroke events, with no major differences among the 3 drugs in the risk of stroke. In conclusion, this study suggests that apixaban has a better safety profile than warfarin and rivaroxaban.

Catheter-directed thrombolysis versus thrombectomy for submassive and massive pulmonary embolism: A systematic review and meta-analysis

IntroductionControversy surrounds the optimal therapy for submassive and massive pulmonary embolism (PE). We conducted a systematic review and meta-analysis to compare the outcomes of catheter-directed thrombolysis (CDT) versus surgical and catheter-based thrombectomy in patients with submassive and massive PE. MethodsWe searched PubMed, EMBASE, Cochrane, and Google Scholar for studies comparing outcomes of CDT versus thrombectomy in submassive and massive PE. Studies were identified and data were extracted by two independent reviewers. A random effects model was used to calculate risk ratios (RRs) with 95 % confidence intervals (CIs). Outcomes included in-hospital mortality, procedural complications, hospital and intensive care unit (ICU) length of stay (LOS), 30-day readmissions, and right ventricle/left ventricle (RV/LV) ratio improvement. ResultsEight observational studies with 1403 patients were included, of whom 50.0 % received CDT. Compared to thrombectomy, CDT was associated with significantly lower in-hospital mortality (RR 0.62; 95 % CI 0.43–0.89; p = 0.01) and similar rates of major bleeding (p = 0.61), blood transfusion (p = 0.41), stroke (p = 0.41), and atrial fibrillation (p = 0.71). The hospital and ICU LOS, 30-day readmissions, and degree of RV/LV ratio improvement were similar between the two strategies (all p > 0.1). In subgroup analyses, in-hospital mortality was similar between CDT and catheter-based thrombectomy (p = 0.48) but lower with CDT compared with surgical thrombectomy (p = 0.01). ConclusionsIn patients with submassive and massive PE, CDT was associated with similar in-hospital mortality compared to catheter-based thrombectomy, but lower in-hospital mortality compared to surgical thrombectomy. Procedural complications, LOS, 30-day readmissions, and RV/LV ratio improvement were similar between CDT and any thrombectomy. Randomized controlled trials are indicated to confirm our findings.

Clinical Outcomes With a Fully Magnetically Levitated Left Ventricular Assist Device Among Women and Men

BackgroundLeft ventricular assist devices (LVADs) are underused among women with advanced heart failure, but reasons remain unclear. Outcomes in women compared with men with contemporary fully magnetically levitated LVADs remain uncertain. ObjectivesThe authors examined differences in characteristics, 2-year outcomes, and risk for key adverse events among women and men. MethodsIn 2,200 HeartMate3 (HM3) (Abbott Cardiovascular) LVAD recipients in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3), survival free of disabling stroke or reoperation to replace or remove a malfunctioning pump at 2 years was analyzed between women and men. Other outcomes included overall 2-year survival, adverse events, and functional measures. ResultsWomen comprised 20.4% (n = 448 of 2,200) of the study population and were younger, with nonischemic cardiomyopathy, and more often were Black persons compared with men. The primary endpoint (women 79.4% vs men 75.5% (adjusted [a]HR: 0.96 [95% CI: 0.75-1.24]; P = 0.66) or survival at 2 years (women 82.4% vs men 80.2%; aHR: 1.06 [95% CI: 0.81-1.40]; P = 0.66) was no different. Women had an increased rate of stroke (adjusted incidence rate ratio [aIRR]: 1.52 [95% CI: 1.09-2.11]; P = 0.012), major bleeding (aIRR: 1.28 [95% CI: 1.15-1.42]; P < 0.0001) and infection (aIRR 1.14 [95% CI: 1.03-1.55]; P = 0.01), but these differences were not seen among older (>65 years) patients. Both groups had similar gains in 6-minute walk distance and quality-of-life measurements. ConclusionsThere were no differences in the primary composite endpoint or overall survival in women compared with men at 2 years of support. Reasons underlying increase in hemocompatibility-related events and infection-related morbidity in younger women deserves further study. (MOMENTUM 3 IDE [HM3], NCT02224755; MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP], NCT02892955)

Cancer-associated splanchnic vein thrombosis: Clinical features upon diagnosis and short-term outcomes

IntroductionThe incidence of splanchnic vein thrombosis (SVT) in cancer patients has increased in recent years and its real clinical significance and management can be challenging. This study aimed to describe the clinical presentation and short-term outcomes of patients with cancer-associated SVT. Material and methodsThis was a retrospective observational study of consecutive patients with cancer-associated SVT diagnosed during the period 2015–2020. The primary objective was to describe the clinical presentation of SVT. Patients were clinically classified into two groups based on the presence of symptoms on SVT diagnosis. The main outcomes were overall and SVT-related mortality, major and non-major bleeding rates, and the thrombosis recurrence rate in the first 30 days of follow-up. ResultsThis study enrolled 203 patients. Intra-abdominal tumors (76 %) and metastatic disease (68 %) predominated. A total of 79 (39 %) patients without symptoms were diagnosed with SVT during a scheduled radiological test and were classified as “asymptomatic”, while 124 (61 %) patients presented some potential SVT symptoms and were considered as “symptomatic”. Although the 30-day outcomes showed no significant differences between the two groups, mortality in the asymptomatic group was slightly lower compared to the symptomatic group (3 % vs. 10 %, p = 0.085). ConclusionsAlmost 40 % of cases of cancer-associated SVT are asymptomatic. There were no significant differences in short-term outcomes between the symptomatic and asymptomatic patients. More studies are required to better define long-term management and outcomes in these patients.

Antiplatelet Treatment Patterns and Outcomes for Secondary Stroke Prevention in the United Kingdom.

Stroke is a leading cause of death and disability worldwide. Antiplatelet therapies are recommended to reduce the risk of recurrent stroke in patients with ischemic stroke/transient ischemic attack (IS/TIA). This study evaluated outpatient antiplatelet treatment patterns and outcomes for secondary stroke prevention (SSP) among UK adults without atrial fibrillation who were hospitalized for IS/TIA. This retrospective observational study utilized data from the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics data (01/01/2011-30/06/2019). Treatment patterns included type and duration of treatments. Treatment outcomes included IS, myocardial infarction, major bleeding, and cardiovascular-related and all-cause mortality. Descriptive statistics were reported. Of 9270 patients, 13.9% (1292) might not receive antithrombotic therapy within 90days of hospital discharge. Of 7978 patients who received antiplatelet therapies, most used clopidogrel (74.8%) or aspirin (16.7%) single antiplatelet therapy and clopidogrel + aspirin dual antiplatelet therapy (DAPT, 5.9%). At 1-year post-hospitalization, 36.9, 43.3, and 35.1% of those receiving these treatments discontinued them, respectively, and of the patients initiating DAPT, 62.3% switched to single antiplatelet therapy. At 1-year post-discharge, the incidence rate (per 100 person-years) of IS, myocardial infarction, major bleeding, cardiovascular-related mortality, and all-cause mortality among the treated were 6.5, 0.7, 4.1, 5.0, and 7.3, respectively, and among the untreated were 14.9, 0.7, 8.6, 28.1, and 39.8, respectively. In the United Kingdom, 13.9% of patients hospitalized for stroke might not have any antiplatelet treatment to prevent secondary stroke; among the treated, clopidogrel, aspirin, and DAPT were commonly used. These study findings suggest that improved anti-thrombotic therapies for long-term SSP treatment are needed, which may lead to higher treatment and persistence rates and, therefore, improved outcomes in this population.

Plasma Fibrinogen Change as a Predictor of Major Bleeding During Catheter-Directed Thrombolysis

Our primary objective was to determine the relationship between plasma fibrinogen levels (PFLs) and major bleeding complications during catheter-directed thrombolysis, including final, nadir, and change over time. Furthermore, we sought to evaluate additional predictors of bleeding outcomes, including duration of lysis and total dose of tissue plasminogen activator received. In this multicenter retrospective cohort study, we reviewed all patients undergoing catheter-directed thrombolysis between January 2016 and August 2021. Patients undergoing thrombolysis for management of peripheral arterial or venous thromboses, as well as for submassive pulmonary embolism, were included. We examined the relationships between PFLs during catheter-directed lysis and the incidence of major bleeding-that is significant hemorrhage requiring transfusion, intracranial hemorrhage, or hemorrhage requiring adjunctive procedures. We also examined the duration of lysis and total lytic agent dose received to assess for association with major bleeding. A total of 438 patients underwent catheter-directed lysis from January 1, 2016 through August 21, 2021, with a major bleeding rate of 16%. Patients who experienced major bleeding were more likely to be older (P=0.022), experience in-stent thrombosis (P=0.041), or have thrombosis in a lower extremity vessel (P=0.011). There was no association between the incidence of major bleeding and a nadir PFL of <150mg/dL (P=0.194). Those who experienced major bleeding complications had a significantly greater decrease in PFL from baseline to nadir. This was true for both absolute (P=0.029) and relative (P=0.034) PFL decrease. Only percent decrease remained a significant predictor when adjusting for age, thrombosis type, and thrombosis location (P=0.041). The PFL changes that were the best predictors of major bleeding complications were an absolute decrease of 146mg/dL, or a relative decrease of 47%, giving a sensitivity and specificity of 71% and 48%, respectively. If neither were true, the negative predictive value for major bleeding was 89% regardless of absolute PFL. In this large, multicenter cohort, there does not appear to be an association between absolute PFL and major bleeding during catheter-directed lysis. Specifically, the typical absolute threshold of < 150mg/dL was not an independent predictor of major bleeding. There was an association between percent-change in plasma fibrinogen and major bleeding, which aligns with the underlying physiologic mechanism of fibrinogen degradation coagulopathy. Applying a so-called "50-150 Rule" to catheter-directed lysis may decrease bleeding complications. That is, continued lysis should be re-evaluated if PFL drops by≥150mg/dL or by≥50% from baseline regardless of absolute PFL.

Midterm follow-up after computed tomography angiography planned left atrial appendage closure.

While studies have shown the advantages of computed tomography angiography (CTA) over transesophageal echocardiography (TEE) in left atrial appendage closure (LAAC) preprocedural planning for WATCHMAN™legacy and FLX devices, there has been no reported long-term data for this approach. We sought to evaluate long-term outcomes using CTA-based preprocedural planning for LAAC using the WATCHMAN™ device. A prospective analysis of 231 consecutive patients who underwent LAAC in a single, large academic hospital in the United States was conducted over a 5-year period. CTA-guided preprocedural planning was performed in all. Procedural success, adverse events, length of procedure, number of devices used, and length of stay were evaluated. Rates of death, cerebral embolism, systemic embolism, and major and minor bleeding were recorded. Adjusted predicted stroke and major bleeding rates were derived from CHA2DS2-Vasc and HAS-BLED scores, respectively. From January 26, 2017, to November 23, 2021, 231 patients underwent LAAC with CTA preprocedural planning by two operating physicians. The mean age of patients was 76.5 ± 8.4. 59.7% of patients were male. Mean CHA2DS2VASc and HAS-BLED scores were 4.5 ± 1.4 and 3.9 ± 0.9, respectively. All procedures were performed with intracardiac echo (100%). The procedural success rate was 99.1%. The CTA sizing strategy accurately predicted the implant size in 93.5% of patients. Mean number of devices used was 1.10 ± 0.3. Peri-procedural complication rate was 2.2%. 6 patients were lost to follow-up. Mean follow-up was 608.94 days with a total of 377.04 patient years. Median follow-up period of 368 days (interquartile range: 209-1067 days). There were 51 deaths from all causes (13.52 per 100 patient-years), 10 cases of cerebral embolism (2.65 per 100 patient-years), 2 cases of systemic embolism (0.53 per 100 patient-years), 17 cases of major bleeding (4.50 per 100 patient-years), and 31 cases of minor bleeding (8.2 per 100 patient-years). All-cause mortality at 1, 2, and 3 years was 12.7%, 20.9%, and 29.2%, respectively. CV event rates at 1, 2, and 3 years were 2.1%, 6.6%, and 10.5%, respectively. CTA-basedpreprocedural planning is accurate in predicting device size for LAAC and associated with excellent clinical outcomes at 5 years.

Association of sex with major bleeding risks in sub-Saharian anticoagulated patients with mechanical heart valves: A cohort study from the Khartoum Emergency Salam Centre.

BackgroundRheumatic heart disease (RHD) with mechanical heart valve (MHV) replacement is common in Africa. However, MHV requires lifelong anticoagulation that could have a particular impact in women in reproductive age. MethodsWe report data of a prospective observational cohort study conducted between August 2018 and September 2019 in MHV patients in the Salam Centre for Cardiac Surgery built in Khartoum by Emergency, an Italian Non-Governmental Organization, to evaluate bleeding risk, its associated determinants, and the impact of lifelong anticoagulation in fertile women. ResultsWe studied 3647 patients (median age 25.1 years; 53.9% female). During follow-up [median time 1.1 (0.1–1.2) years], we recorded 85 major bleedings (rate 2.16 × 100 pt-years), Major bleedings occurred more frequently among women (64/85 cases, 75.3%; rate 3.0 × 100 pt-years), compared to men (21/85 cases, 24.7%; rate 1.16 × 100 pt-years) (RR 2.6; 95% CI 1.6–4.5; p = 0.0001). Multivariate analysis was performed to identify variables associated with major bleeding, and female sex was the only risk factor significantly associated, whereas aspirin treatment and higher INR target showed a non-significant trend for higher bleeding risk. Thirty-two/85 (37.6%) of major bleedings were metrorrhagias. When we calculate the incidence of major bleedings after the exclusion of gynecological events, no sex differences in the bleeding risk were found (HR 1.3, 95% CI 0.8–2.3; p = 0.3). ConclusionsBleeding risk of young MHV patients on oral anticoagulant therapy is higher among women, mainly due to metrorrhagia. Women in the reproductive life are at high risk for gynecological bleeding when treated with anticoagulants.