Long-term Bleeding Risk Research Articles

Anticoagulant therapy in venous thromboembolism and bleeding risk: focus on the use of predictive scores.

The standard treatment for venous thromboembolism (Vte) is anticoagulation. Drug selection and treatment duration will depend on the clinical presentation, the existence of provoking factors, bleeding risk, and the patient's preferences. Anticoagulation therapy is indicated for 3-6 months in all patients with acute Vte but may be extended, even indefinitely in some cases. The most severe side effect of anticoagulation is bleeding, with the highest risk occurring during the 1st months of therapy. Balancing the risk of bleeding and the risk of recurrence in patients with Vte remain a major issue. There are, currently, no simple and validated predictive scores to estimate the long-term bleeding risk in patients undergoing anticoagulant treatment and to safely select those patients with higher bleeding risk. In this review we will examine some of these scores, including the RIETE scores, the HAS-BLED SCORE, the VTE-BLEED score, the VTE- PREDICT and the ACCP guidelines and the timing for their application in the patient's population treated for Vte as well as the initial and long-term management and evaluation of thromboembolic disease.

STENOSIS: Long-term single versus dual antiplatelet therapy in patients with ischaemic stroke due to intracranial atherosclerotic disease – a randomised trial

RationaleIntracranial atherosclerotic disease (ICAD) is a pathological process that causes progressive stenosis and cerebral hypoperfusion, leading to stroke occurrence and recurrence around the world. The exact duration of dual antiplatelet...

L-shaped association of lipoprotein(a) on long-term bleeding risk in patients with coronary heart disease: insight from a multicenter cohort in Asia

Abstract Background Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD. Methods Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up. Results A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2-5 (p < 0.001), while the incidence of major bleeding seemed similar between two groups. Moreover, restricted cubic spline analysis suggested that there was a L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding. Conclusion There was the inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)’s role, as a novel marker for bleeding risk in order to better guide shared-decision making in clinical practice.Figure 1

Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia.

Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD. Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up. A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (p < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding. There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.

Freedom from atrial arrhythmia and other clinical outcomes at 5 years and beyond after catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

Catheter ablation of atrial fibrillation (AF) is now a mainstream procedure although long-term outcomes are uncertain. We performed a systematic review and meta-analysis of procedural outcomes at 5 years and beyond. We searched PubMed and Embase and after the screening, identified 73 studies (67159 patients) reporting freedom from atrial arrhythmia, all-cause death, stroke, and major bleeding at≥5 years after AF ablation. The pooled mean age was 59.7y, 71.5% male, 62.2% paroxysmal AF, and radiofrequency was used in 78.1% of studies. Pooled incidence of freedom from atrial arrhythmia at 5 years was 50.6% (95%CI 45.5-55.7%) after a single ablation and 69.7% [95%CI (confidence interval) 63.8-75.3%) after multiple procedures. The incidence was higher among patients with paroxysmal compared with non-paroxysmal AF after single (59.7%vs. 33.3%, p=0.002) and multiple (80.8%vs. 60.6%, p<0.001) ablations but was comparable between radiofrequency and cryoablation. Pooled incidences of other outcomes were 6.0% (95%CI 3.2-9.7%) for death, 2.4% (95%CI 1.4-3.7%) for stroke, and 1.2% (95%CI 0.8-2.0%) for major bleeding at 5 years. Beyond 5 years, freedom from arrhythmia recurrence remained largely stable (52.3% and 64.7% after single and multiple procedures at 10 years), while the risk of stroke and bleeding increased over time. Nearly 70% of patients having multiple ablations remained free from atrial arrhythmia at 5 years, with the incidence slightly decreasing beyond this period. Risk of death, stroke, and major bleeding at 5 years were low but increased over time, emphasizing the importance of long-term thromboembolism prevention and bleeding risk management.

External validation of bleeding risk models for the prediction of long-term bleeding risk in patients with established cardiovascular disease

ObjectiveThe long-term predictive performance of existing bleeding risk models in patients with various manifestations of cardiovascular disease (CVD) is not well known. This study aims to assess and compare the performance of relevant existing bleeding risk models in estimating the long-term risk of major bleeding in a cohort of patients with established CVD. MethodsSeven existing bleeding risk models (PRECISE-DAPT, DAPT, Ducrocq et al, de Vries et al, S2TOP-BLEED, Intracranial B2LEED3S and HAS-BLED) were identified and externally validated in 7,249 patients with established CVD included in the Utrecht Cardiovascular Cohort–second manifestations of arterial disease study. Predictive performance was assessed in terms of discrimination and calibration, both at 10 years and the original prediction horizon of the models. Major bleeding was defined as Bleeding Academic Research Consortium type 3 or 5. ResultsAfter a median follow-up of 8.4 years (interquartile range 4.5-12.5), a total of 233 (3.2%) major bleeding events occurred. C-statistics for discrimination at 10 years ranged from 0.53 (95%CI 0.49-0.57) to 0.64 (95%CI 0.60-0.68). Calibration plots after recalibration to 10 years showed best agreement between predicted and observed bleeding risk for De Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. ConclusionsThe performance of existing bleeding risk models to predict long-term bleeding in patients with CVD varied. Discrimination and calibration were best for the models of de Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. Of these, recalibrated models requiring the least predictors may be preferred for use to personalize prevention with antithrombotic therapy.

Long-term stroke and major bleeding risk in patients with non-valvular atrial fibrillation: A comparative analysis between non-vitamin K antagonist oral anticoagulants and warfarin using a clinical data warehouse.

Non-vitamin K antagonist oral anticoagulants (NOACs) has been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation (AF) since 2014. Many studies based on claim data revealed that NOACs had comparable effect to warfarin in preventing ischemic stroke with fewer hemorrhagic side effects. We analyzed the difference in clinical outcomes according to the drugs in patients with AF based on the clinical data warehouse (CDW). We extracted data of patients with AF from our hospital's CDW and obtained clinical information including test results. All claim data of the patients were extracted from National Health Insurance Service, and dataset was constructed by combining it with CDW data. Separately, another dataset was constructed with patients who could obtain sufficient clinical information from the CDW. The patients were divided NOAC and warfarin groups. The occurrence of ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, and death were confirmed as clinical outcome. The factors influencing the risk of clinical outcomes were analyzed. The patients who were diagnosed AF between 2009 and 2020 were included in the dataset construction. In the combined dataset, 858 patients were treated with warfarin, 2,343 patients were treated with NOACs. After the diagnosis of AF, the incidence of ischemic stroke during follow-up was 199 (23.2%) in the warfarin group, 209 (8.9%) in the NOAC group. Intracranial hemorrhage occurred in 70 patients (8.2%) among the warfarin group, 61 (2.6%) of the NOAC group. Gastrointestinal bleeding occurred in 69 patients (8.0%) in the warfarin group, 78 patients (3.3%) in the NOAC group. NOAC's hazard ratio (HR) of ischemic stroke was 0.479 (95% CI 0.39-0.589, p < 0.0001), HR of intracranial hemorrhage was 0.453 (95% CI 0.31-0.664, p < 0.0001), and HR of gastrointestinal bleeding was 0.579 (95% CI 0.406-0.824, p = 0.0024). In the dataset constructed using only CDW, the NOAC group also had a lower risk of ischemic stroke and intracranial hemorrhage than warfarin group. In this CDW based study, NOACs are more effective and safer than warfarin in patients with AF even with long-term follow-up. NOACs should be used to prevent ischemic stroke in patients with AF.

Abstract 10844: Black Race and Risk of Bleeding Events in Patients With Durable Left Ventricular Assist Devices

Introduction: An analysis from the MOMENTUM 3 trial showed that black patients have an increased risk of bleeding compared to white patients. We sought to examine racial differences in the risk of long term bleeding (up to 3 years) in patients with cf-LVADs using the INTERMACS database. Hypothesis: Black race is associated with an increased risk of bleeding events after cf-LVAD. Methods: We included 11,457 patients from the INTERMACS registry, who were implanted with primary CF-LVAD between 2012-2017. Using a cox proportional hazards model, we assessed the relationship between race and bleeding events up to 3 years post LVAD implantation after adjusting for covariates*. Analysis was started at 3 months post implantation to focus on long-term bleeding risk rather than early, post-operative bleeding. These bleeding events were stratified for the two major types of bleeding, GI bleeding (GIB) and intracranial hemorrhage (ICH). Results: This study included 2884 black patients (25.8%) and 8505 non-black patients (74.2%). Black patients tended to be younger (52.2 vs 58.6 yr p&lt;0.001) with more women (30.9% vs 17.7% p&lt;0.001) when compared to non-black patients. There were 1442 black patients who had a bleeding event vs 3972 non-black patients (50.0% vs 46.7% p=0.007) over 3 years of follow up (Fig 1). After adjusting for age, sex, and other covariates*, we found that black patients were more likely to have any bleeding event post LVAD implantation compared to non-black patients (adj HR 1.19 p&lt;0.0001). When stratified by type of bleeding, the risk of ICH was similar between the two groups (10.8% vs 9.2%, adj HR 1.12, p 0.35), but the risk of GIB was higher among black vs non-black patients (30.9% vs 29.6%; adj HR 1.36, p&lt;0.0001). Conclusions: Black patients have a higher risk of long term bleeding and specifically GIB after LVAD implantation. Further studies are warranted to elucidate this relationship and potential clinical implications including anticoagulation strategies.

Bleeding after percutaneous coronary intervention and selection of candidates for long-term dual antithrombotic treatment

Abstract Background The European Society of Cardiology recommends addition of a second antithrombotic drug (a P2Y12 inhibitor or rivaroxaban 2.5 mg twice daily) on top of aspirin in selected patients with chronic coronary syndrome (CCS) at high residual risk of ischemic events. However, this treatment increases bleeding risk, and identifying subsets of patients with the most favorable trade-off between ischemic and bleeding risk thus is essential. We hypothesized that patients undergoing percutaneous coronary intervention (PCI) who tolerate subsequent dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) without any bleeding complications selected themselves as candidates for prolonged dual antithrombotic therapy. Methods and results We included 30,531 patients with CCS treated with dual antiplatelet therapy after first-time PCI with a drug-eluting stent in Western Denmark (3.5 million inhabitants) from 1999 to 2018. Of these, 1,220 (4%) were hospitalized for bleeding within one year after PCI (bleeders) and 29,311 (96%) were not (non-bleeders). Patients were followed for maximum nine years (median follow-up 5.4 years). Bleeders had an increased nine-year risk of death (adjusted hazard ratio [aHR] 1.54, 95% CI 1.37–1.73) and hospitalization for bleeding (aHR 2.53, 95% CI 2.20–2.90). These associations were particularly strong for women. Looking at types of bleeding, the strongest predictors of death were gastrointestinal bleeding, cerebral bleeding, and anemia due to bleeding. Risks of myocardial infarction and ischemic stroke did not differ between bleeders and non-bleeders (Table). We then stratified non-bleeders according to their thromboembolic risk using the CHADS-P2A2RC score – a validated clinical risk prediction model developed to estimate thromboembolic risk in patients without atrial fibrillation. Non-bleeders with a high estimated thromboembolic risk (CHADS-P2A2RC score ≥4) had higher nine-year risks of myocardial infarction (hazard ratio [HR] 1.88, 95% CI 1.78–2.07), ischemic stroke (HR 3.02, 95% CI 2.66–3.43), hospitalization for bleeding (HR 1.98, 95% CI 1.81–2.16) and, in particular, death (HR 4.48, 95% CI 4.21–4.77) than non-bleeders with a low-to-moderate predicted risk (CHADS-P2A2RC score &amp;lt;4). Conclusions Patients with CCS experiencing a bleeding event during the first year after first-time PCI had a substantially higher long-term risk of death and recurrent bleeding, but not a higher risk of ischemic events. Therefore, bleeding events during the first year after PCI may guide the preclusion of selected patients from long-term dual antithrombotic therapy. Among non-bleeders, the risk of ischemic events rose proportionately more than the risk of bleeding when comparing high-risk with low-risk patients. This is an important finding for clinicians, for whom accurate identification of patients at highest risk of ischemic events is an essential step in treatment allocation. Funding Acknowledgement Type of funding sources: None.

Long-term clinical outcomes in older patients with acute venous thromboembolism who have renal impairment

IntroductionRenal impairment (RI) may induce an inflammatory/procoagulant state as well as platelet dysfunction. Little is known on the prevalence of RI and long-term prognosis of older patients with venous thromboembolism (VTE) who have concomitant RI. MethodsIn a prospective multicenter cohort, we analyzed 912 patients aged ≥65 years with acute VTE. Using the CKD-EPI formula, we defined three categories of baseline renal function: estimated glomerular filtration rate ≥60 ml/min/1.73m2 (no RI), 30–59 ml/min/1.73m2 (moderate RI), and <30 ml/min/1.73m2 (severe RI). The outcomes were VTE recurrence, major bleeding, and overall mortality. We examined the association between renal function and clinical outcomes using competing risk regression models, adjusting for relevant confounders and periods of anticoagulation. ResultsWe followed 912 patients over a median duration of 29.6 months. Overall, 313 (34%) patients had moderate and 51 (6%) severe RI. One hundred and seven patients (12%) had VTE recurrence, 125 (14%) had major bleeding, and 186 (20%) died during follow-up. After adjustment, severe RI was associated with a 2-fold increased risk of major bleeding (sub-hazard ratio [SHR] 2.1, 95% CI 1.1–4.0) compared to no RI, but not with VTE recurrence (SHR 0.6, 95% CI 0.2–1.8) or overall mortality (hazard ratio 1.0, 95% CI 0.6–1.9). Moderate RI was not significantly associated with adverse clinical outcomes. ConclusionsRI was common among older patients with acute VTE. Severe RI was associated with a 2-fold increased long-term risk of major bleeding, without a risk increase in terms of VTE recurrence and overall mortality. Older patients with moderate RI did not carry worse prognosis.

Association of baseline hemoglobin A1c levels with bleeding in patients with non-ST-segment elevation acute coronary syndrome underwent percutaneous coronary intervention: insights of a multicenter cohort study from China.

OBJECTIVETo investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI).METHODSThis observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTSOf patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONSCompared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.

Comparative Outcomes After Percutaneous Coronary Intervention in Unconscious and Conscious Patients WithOut-of-Hospital Cardiac Arrest.

Up to 70% of out-of-hospital cardiac arrest (OHCA) patients have a relevant coronary stenosis which may need revascularization. The short- and long-term ischemic and bleeding risk of unconscious and conscious OHCA patients undergoing percutaneous coronary intervention (PCI) is largely unknown. This study sought to compare the occurrence of 1-year outcomes after PCI between OHCA patients, stratified on the basis of state of consciousness, with patients with acute coronary syndrome (ACS) not preceded by OHCA. The study assessed the unadjusted and adjusted risk of cardiovascular events in a prospective single-center cohort of 9,303 consecutive PCI patients. At 1 year, all-cause mortality was higher in unconscious (49.5%) but not in conscious OHCA (8.9%) patients than in ACS patients (8.0%), and both unconscious and conscious OHCA patients were more likely than ACS patients to experience definite stent thrombosis (4.4% and 3.5% vs 1.3%) and Bleeding Academic Research Consortium 3 or 5 bleeding (17.8% and 9.0% vs 5.1%). The higher hazards were largely determined by events occurring in the first 30days. After multivariable adjustment, only unconscious OHCA patients remained at increased risk of death (adjusted HR: 3.27; 95%CI: 2.65-4.05), definite stent thrombosis (adjusted HR: 2.40; 95%CI: 1.30-4.43), and Bleeding Academic Research Consortium 3 or 5 bleeding (adjusted HR: 2.51; 95%CI: 1.82-3.47) at 1 year. At 1 year after PCI, unconscious OHCA patients were at higher risk of death, definite stent thrombosis, and bleeding, while conscious OHCA patients had similar hazards compared with an all-comer ACS population without OHCA. Dedicated PCI strategies for OHCA patients taking into account their state of consciousness after resuscitation are warranted.

Increased long-term bleeding complications in females undergoing endovascular revascularization for peripheral arterial disease

ObjectiveFemales with peripheral arterial disease (PAD) treated with endovascular interventions have increased limb-based procedural complications compared with males. Little is known regarding long-term bleeding risk in these patients who often require long-term antiplatelet or anticoagulation therapy. We hypothesize that females have a higher incidence of bleeding events compared with males in the year after endovascular intervention for PAD. MethodsAdults (aged ≥65 years) who underwent endovascular revascularization for PAD between 2008 and 2015 in Medicare claims data were identified. Patients were allocated by prescribed postprocedural antithrombotic therapy, including (1) antiplatelet therapy, (2) anticoagulation therapy, (3) dual antiplatelet and anticoagulation therapy, and (4) no prescription antithrombotic therapy. Bleeding events were classified as gastrointestinal, intracranial, hematoma, airway, or other. Crude and covariate-standardized 30-, 90-, and 365-day cumulative incidence of bleeding events, overall and by sex, were estimated using Aalen-Johansen estimators accounting for death as a competing risk. Sex differences were identified using Gray’s test. ResultsOf 31,593 eligible patients, 54% were females. Females were older (77.9 years vs 75.5 years) and tended to use antiplatelet therapy more often at 30, 90, and 365 days after the intervention. Clopidogrel was the most prescribed antiplatelet, and 32% of patients continued its use at 365 days. Anticoagulants were prescribed to 26.0% of patients at the time of the procedure, and only 8.8% continued anticoagulation at 365 days. Thirty-one percent of patients were diagnosed with a bleeding event within 1 year after the intervention. The cumulative incidence of any bleeding event during the postintervention period was higher in females compared with males with a risk difference of 3% between the sex cohorts (P < .01). Specifically, females had a higher incidence of gastrointestinal bleeding and hematoma (P < .01), but a lower incidence of airway-related bleeding at each time point as compared with males (P < .01). ConclusionsSex disparities in bleeding complications after endovascular intervention for PAD persist in the long term. Females are more likely to be readmitted with a bleeding complication up to 1 year after the procedure. Antithrombotic therapy disproportionately increases the risk of bleeding in females. Further research is necessary to understand the mechanisms responsible for abnormal coagulopathy in females after endovascular therapy.

Long-term Risk of Bleeding and Ischemic Events After Ischemic Stroke or Transient Ischemic Attack in Young Adults.

Guidelines recommend antithrombotic medication as secondary prevention for patients with ischemic stroke or transient ischemic attack (TIA) at young age based on results from trials in older patients. We investigated the long-term risk of bleeding and ischemic events in young patients after ischemic stroke or TIA. We included 30-day survivors of first-ever ischemic stroke or TIA aged 18-50 years from the Follow-Up of TIA and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) study, a prospective cohort study of stroke at young age. We obtained information on recurrent ischemia based on structured data collection from 1995 until 2014 as part of the FUTURE study follow-up, complemented with information on any bleeding and ischemic events by retrospective chart review from baseline until last medical consultation or June 2020. Primary outcome was any bleeding; secondary outcome any ischemic event during follow-up. Both were stratified for sex, age, etiology, and use of antithrombotic medication at discharge. Bleeding and ischemic events were classified according to location and bleeding events also by severity. We included 544 patients (56.1% women, median age of 42.2; interquartile range [IQR] 36.5-46.7 years) with a median follow-up of 9.6 (IQR 2.5-14.3) years. Ten-year cumulative risk of any bleeding event was 21.8% (95% CI 17.4-26.0) and 33.9% (95% CI 28.3-37.5) of any ischemic event. Risk of bleeding was higher in women with a cumulative risk of 28.2% (95% CI 21.6-34.3) vs 13.7% (95% CI 8.2-18.9) in men (p < 0.01), mainly because of gynecologic bleeds. Female sex (p < 0.001) and age between 40 and 49 years (p = 0.04) were independent predictors of bleeding. Young patients after ischemic stroke or TIA have a substantial long-term risk of both bleeding (especially women) and ischemic events. Future studies should investigate the effects of long-term antithrombotics in young patients, taking into account the risk of bleeding complications.

Effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and β-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.

Short-term, medium-term, and long-term risks of nonvariceal upper gastrointestinal bleeding after dengue virus infection.

Dengue patients have an increased risk of acute gastrointestinal (GI) bleeding. However, whether dengue virus (DENV) infection can cause an increased long-term risk of GI bleeding remains unknown, especially among elderly individuals who commonly take antithrombotic drugs. A retrospective population-based cohort study was conducted by analyzing the National Health Insurance Research Databases. Laboratory-confirmed dengue patients from 2002 to 2012 and four matched nondengue controls were identified. Multivariate Cox proportional hazard regression was used to evaluate the acute (<30 days), medium-term (31–365 days), and long-term (>365 days) risks of nonvariceal upper GI bleeding after DENV infection. Stratified analyses by age group (≤50, 51–64, ≥65 years old) were also performed. In total, 13267 confirmed dengue patients and 53068 nondengue matched controls were included. After adjusting for sex, age, area of residence, comorbidities, and medications, dengue patients had a significantly increased risk of nonvariceal upper GI bleeding within 30 days of disease onset (adjusted HR 55.40; 95% CI: 32.17–95.42). However, DENV infection was not associated with increased medium-term and long-term risks of upper GI bleeding overall or in each age group. Even dengue patients who developed acute GI bleeding did not have increased medium-term (adjusted HR; 0.55, 95% CI 0.05–6.18) and long-term risks of upper GI bleeding (adjusted HR; 1.78, 95% CI 0.89–3.55). DENV infection was associated with a significantly increased risk of nonvariceal upper GI bleeding within 30 days but not thereafter. Recovered dengue patients with acute GI bleeding can resume antithrombotic treatments to minimize the risk of thrombosis.

Long-Term Risk of Major Bleeding after Discontinuing Anticoagulation for Unprovoked Venous Thromboembolism: A Systematic Review and Meta-analysis.

The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE. We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked or weakly provoked VTE who had completed (IMAGE_)3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies. Of 1,123 records identified by the search, 20 studies (17 RCTs) and 8,740 patients were included in the analysis. During 13,011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n = 41) and fatal bleeding (n = 7) per 100 person-years was 0.35 (95% confidence interval [CI]: 0.20-0.54) and 0.09 (95% CI: 0.05-0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI: 0.4-2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI: 10.6-31.1%). The risk of major bleeding once anticoagulants are discontinued in patients with a first unprovoked VTE is not zero. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.

Association between platelet reactivity and long-term bleeding complications following percutaneous coronary intervention in patients with and without diabetes

Abstract Background The association between diabetes mellitus (DM) and bleeding complications following percutaneous coronary intervention (PCI) is controversial. We hypothesized that on-treatment platelet reactivity may have a role in the bleeding risk stratification of such patients. Purpose To investigate the role of low platelet reactivity (LPR) in the long-term bleeding risk stratification among patients with and without diabetes undergoing PCI. Methods In this observational, retrospective single-center study, 472 patients undergoing PCI for stable coronary artery disease were included. All patients were treated with dual antiplatelet therapy with aspirin and clopidogrel. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay and LPR was defined by values of platelet reactivity unit (PRU) ≤178. Primary endpoint was the occurrence of all bleeding events at 5 years stratified by DM status and LPR. Results Out of the study population included, 30.5% had DM (N=144). LPR was numerically less frequent in patients with DM compared to those without (29.2% vs 37.6%; p=0.077). Overall, 11.9% of patients experienced a bleeding complication at 5-year follow-up; 44.6% of events were classified as major bleedings. The incidence of bleeding events per 1000 patients-year was 34.5 (95% CI 22.3–53.5) in DM and 24.2 (95% CI 17.3–33.8) in no DM (p=0.24). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without DM and LPR (log-rank p=0.004), with those having both conditions being at the highest risk of events (Figure). LPR had a similar value for stratifying the risk of bleeding in patients with and without diabetes (p value for interaction between diabetes and LPR status=0.45). Conclusions Approximately 1 out of 3 patients undergoing PCI for stable coronary artery disease on clopidogrel has LPR. The assessment of LPR provides a significant incremental value for the prediction of bleeding events irrespective from DM status. While the presence of DM per se does not increase the risk of bleeding complications, the coexistence of DM and LPR identifies the subgroup at the highest risk of events who could benefit from a short-term and less intensive antiplatelet regimen. Funding Acknowledgement Type of funding sources: None.

Long-term risk of upper gastrointestinal bleeding after Helicobacter pylori eradication: a population-based cohort study.

The long-term effects of H. pylori eradication in preventing upper GI bleeding (UGIB) remains unknown. To determine the long-term risks of UGIB after H. pylori eradication METHODS: We included all patients who had received clarithromycin-containing triple therapy for the treatment of H. pyliori infection between 2003 and 2012, without subsequent need for re-treatment. We included a propensity score (PS)-matched endoscopy cohort of H. pylori-negative patients as controls. The primary endpoint was the risk of subsequent UGIB. A multivariable Cox model was used to compute the hazard ratio (HR) of UGIB. We included 62738 H. pylori-eradicated and 62738 PS-matched H. pylori-negative patients, with a median follow-up of 8.1years (IQR 5.5-10.6). The incidence of UGIB was 20.8 (95% CI 19.5-22.1) and 13.6 (95% CI 12.7-14.7) per 10000 person-years in H. pylori-eradicated and H. pylori-negative patients, respectively. Compared to controls, H. pylori-eradicated patients had a significantly higher risk of UGIB (HR: 1.65, 95% CI 1.49-1.83). The risk of UGIB in H. pylori-eradicated patients increased after the first 2 years of follow up (HR: 2.18, 95% CI 1.91-2.49). Age-stratified analysis showed that patients >45years had higher UGIB risk, even after eradication. Despite H. pylori eradication, the long-term risk of UGIB was still higher than in H. pylori-negative control subjects. The protective effects of eradication therapy in preventing UGIB appeared to be limited to younger patients, and to within the first 2 years after eradication.

A Decision Model to Estimate Risk Thresholds for Guiding Duration of Anticaogulation in Unprovoked Venous Thromboembolism

▪Background: For patients with a first unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulant therapy (AT) is a crucial clinical dilemma which has yet to be resolved . Choosing short-term (3-6 months) or indefinite AT, requires balancing the long-term risk of recurrent VTE when AT is discontinued, with the long-term risk of major bleeding (MB) from extended AT. Current guidelines suggest considering indefinite AT in all unprovoked VTE patients with non-high bleeding risk. This however, is a weak-evidence recommendation based on limited data, and no precise risk thresholds have been established to help guide treatment duration in this patient population. From an economic perspective, we aimed to identify thresholds of the risk of MB and recurrent VTE for which indefinite AT, as compared to stopping AT after initial short-term treatment, may be warranted.Methods: We constructed a Markov decision model of patients with a first unprovoked VTE who had completed at least 3-6 months of initial AT. The model adopted a lifetime horizon and a publicly-funded healthcare system perspective. Using a cycle length of one year, the model tracked recurrent VTE (DVT and/or PE), MB, and death from any cause [Figure 1]. For the base case, we considered patients aged 57 years, having a life expectancy of 30 years, annual risk of MB on Vitamin K Antagonists of 1.5%, annual recurrent VTE risk of 5% per year off therapy, case-fatality-rate (CFR) for MB of 11.3%, and CFR for recurrent VTE of 3.6%. We expressed our results as Incremental Net Benefit (INB) which incorporates costs, life-expectancy, quality-adjusted life-years (QALYs), and a willingness to pay (WTP) value. INB is the incremental benefit, expressed in monetary terms ($), of offering a patient treatment (indefinite AT) rather than the comparator (stopping AT). An INB > 0 favours the treatment, whereas an INB < 0 favours the comparator.Results: For the base case analysis with assuming a decision-maker's WTP threshold of $50,000/QALY, indefinite AT was not justified (i.e. INB < 0) when the annual risk of recurrent VTE off therapy was less than 7.1% [Figure 2], or when the annual risk of MB exceeded 2.4% [Figure 3]. Furthermore, in a two-way sensitivity analysis [Figure 4], as the MB risk increased, so did the recurrent VTE risk threshold for which indefinite AT would be warranted. As illustrated through three hypothetical situations outlined in Figure 4; for a patient with an annual MB risk of 3.5% [scenario A], a recurrence risk of >15% would be required for indefinite AT to be favorable (i.e. INB > 0). Similarly, using a base case annual MB risk of 1.5% [scenario B], from an economic standpoint, the decision to offer indefinite AT would not be preferred for a patient in whom the risk of recurrence is 3%, but may be supported for a patient in whom the risk of recurrence is 10%. Lastly, for a patient with an annual recurrent VTE risk of < 1% [scenario C], continuing AT indefinitely would never be justified, irrespective of the risk of MB.Conclusions/Implications: To the best of our knowledge, this is the first decision analysis of a hypothetical cohort of unprovoked VTE patients that identifies risk thresholds of MB and recurrent VTE to guide treatment duration. From an economic viewpoint, our analysis demonstrates that choosing indefinite AT in such patients may not be justified at the proposed risk thresholds. Furthermore, long-term follow up demonstrates that VTE recurs in less than 50% of such patients after stopping AT;thus, considering indefinite AT in all unprovoked VTE patients is an inefficient use of resources, and exposes a large proportion of patients to the unnecessary risks, burdens and costs of lifelong AT. Establishing risk thresholds, as achieved through our decision model, allows individualized treatment and helps guide patient-centered decision making. If validated and further optimized (as planned prior to the ASH), findings from our study could change clinical practice. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.