Risk Factors For Major Bleeding Research Articles

Incidence and risk factors for major bleeding events in atrial fibrillation patients on direct oral anticoagulant therapy: data from the National Patient-Centered Clinical Research Network

Abstract Background Direct oral anticoagulation (DOACs) prevent stroke in patients with atrial fibrillation (AF) and have a superior safety profile compared with vitamin K antagonists (VKA). Yet, better definition of incidence and risk factors for major bleeding associated with DOACs in clinical practice may be important given emerging stroke prevention technologies, both pharmacologic and nonpharmacologic. Purpose To describe the incidence of and risk factors for major bleeding in individuals with AF on DOAC therapy. Methods We reviewed electronic health record data for two patient cohorts with AF prescribed DOACs: (1) Duke University Health System (DUHS) (2010–2018) and (2) Sites within the Patient-Centered Clinical Research Network (PCORnet) (2015–2019) which had ≥6 years assimilated data from both inpatient and outpatient encounters (7 sites). In each cohort, we assessed the 5-year incidence of major bleeding events defined as hospitalization for intracranial hemorrhage, or hospitalization for gastro-intestinal bleeding or procedure to control bleeding accompanied by transfusion within ±7 days or death within 30 days. Multivariable Fine-Gray proportional hazards modeling in each cohort was performed to evaluate independent risk factors for major bleeding on DOAC therapy. Results The cohorts included 10,625 patients (DUHS) and 58,321 patients (PCORnet) with AF. Major bleeding events occurred within 5 years of diagnosis in 639 (7.9%) of DUHS patients and 2568 (6.6%) of PCORnet patients (Table 1). The DUHS model predicted time to first major bleeding event with a C-index of 0.756 (95% CI 0.737, 0.775) and the PCORNet model had a c-index of 0.745 (0.736, 0.755) (Table 2). Independent factors associated with major bleeding consistent across both models (p<0.001 in PCORnet for all unless noted) were higher CHA2DS2-VASc scores, lower eGFR, anemia (HR per 1-point increase in hemoglobin up to 12 g/dL 0.79 [0.76, 0.82]), prior major bleeding (HR 2.70 [2.22, 3.30]), cancer (HR 1.23 [1.12, 1.36]), recent cardiac surgery (HR 0.70 [0.51, 0.97]; p=0.030), alcohol use (HR 1.56 [1.29, 1.88]), aspirin use (HR 1.44 [1.32, 1.57]), and selective serotonin reuptake inhibitor use (HR 1.30 [1.19, 1.42]). Conclusions Across a large and geographically diverse contemporary population, risk of bleeding on DOAC for stroke prevention in AF remains a frequent and important clinical problem. There is an unmet need for stroke prevention therapies with improved safety profiles. We identified risk factors for major bleeding events on DOAC therapy, some of which are not represented in traditional risk scores, which may inform shared decision making for stroke prevention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer Pharmaceuticals

Performance of stent thrombosis and bleeding risk scores in out-of-hospital cardiac arrest due to acute coronary syndromes

BackgroundPatients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated. MethodsAll consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores. ResultsAmong 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05; P=0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88–0.98; P=0.010 and OR 0.61; 95% CI 0.41–0.89; P=0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18–3.73; P=0.011) were independent risk factors for major bleeding. ConclusionThe classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study

BackgroundThe coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear.MethodThe CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events.ResultsAmong 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6–14] vs 28 [19–43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001).ConclusionsIn the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Validation of thrombotic risk factors in 1381 patients with essential thrombocythaemia: A multicentre retrospective real-life study.

Thrombosis and haemorrhage are frequent in patients with essential thrombocythaemia (ET). The 2016 revised International Prognostic Score for Thrombosis in Essential Thrombocythaemia-thrombosis (r-IPSET-t) score stratifies patients into very-low- (VLR), low- (LR), intermediate- (IR) and high-risk (HR) groups. We validated the r-IPSET-t in the biggest population of patients with ET (n=1381) to date and found it to be a better fit than the earlier IPSET-t score. With an average follow-up of 87.7 months, there were 0.578 thrombotic events/person-year and 0.286 bleeding events/person-year after diagnosis. The 10-year thrombosis-free survival was 88% and 99% for the r-IPSET-t LR and VLR groups (p < 0.001). Cytoreduction was a thrombotic risk factor in younger patients (aged <60 years, hazard ratio 9.49, p=0.026; aged ≥60 years, hazard ratio 1.04, p=0.93). In multivariable Cox regression analysis, anti-aggregation after diagnosis was protective for thrombosis (hazard ratio 0.31, p=0.005) but a risk factor for major bleeding (hazard ratio 10.56, p=0.021). Of the IPSET-t HR and LR groups, 132/780 and 249/301 were re-classified as LR and VLR respectively (p < 0.001). The European LeukemiaNET (ELN) does not recommend aspirin for VLR patients but in this real-life analysis 83.1% of VLR patients received it. Our results validate the r-IPSET-t score as more predictive for thrombosis than the ELN-recommended IPSET-t and raise concerns about unnecessary cytoreductive and anti-aggregative therapy.

Bleeding and thrombotic complications in patients with severe COVID-19: A prospective observational study.

Bleeding and thrombotic complications in patients with severe COVID-19: A prospective observational study.

Clinical Performance of Oral Anticoagulants in Elderly with Atrial Fibrillation and Low Body Weight: Insight into Italian Cohort of PREFER-AF and PREFER-AF Prolongation Registries.

Background: Elderly patients are at high risk of both ischaemic and bleeding events, and the low body weight is considered a risk factor for major bleeding in atrial fibrillation (AF) patients on anticoagulation therapy. The aim of our study was to compare the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus well-controlled vitamin-K antagonists (VKA) therapy among AF patients aged >75 years and with a body weight <60 kg in a prospective registry setting. Methods: Data for this study were sourced from the Italian cohorts of PREFER in AF and PREFER in AF PROLONGATION registries. The occurrence of a composite of stroke, transient ischemic attack and systemic embolism (thromboembolic events) was the primary effectiveness endpoint. The occurrence of major bleeding was the primary safety endpoint. All-cause hospitalizations and all-cause death were the secondary endpoints. The net clinical benefit (NCB) was calculated in order to obtain an integrated assessment of the anti-thromboembolic and pro-haemorrhagic effects of NOACs vs. VKA. Results: Overall, 522 patients were included; 225 were on treatment with NOACs and 317 patients with VKA. The NOAC group more frequently featured a higher BMI and a higher prevalence of history of stroke/TIA and insulin-requiring diabetes; conversely, heart failure and chronic liver disease were less frequent in the NAOC group. In the unmatched study population, 18 patients (3.6% in the NOAC vs. 3.2% in the VKA group, p = 0.79) experienced thromboembolic events; 19 patients (1.78% in the NOAC vs. 4.73% in the VKA group, p = 0.06) experienced major bleeding events; and 68 patients were hospitalized during the follow-up (9.3% vs. 14.8%, p = 0.06). After balancing for potential confounders by using the 1:1 propensity score matching technique, 426 patients (213 on NOAC and 213 on VKA) were selected. We found no significant differences in terms of thromboembolic events (3.76% vs. 4.69%, p = 0.63), major bleeding events (n: 1.88% vs. 4.22%, p = 0.15) and hospitalizations (9.9% vs. 16.9%, p = 0.06) between NOAC vs. VKA matched population. Based on these incidences, we found a positive net clinical benefit (+1.6) of NOACs vs. VKAs. Conclusions: These real-world data suggest the safety and effectiveness of using NOACs in elderly patients with low body weight.

Risk Factors of Unfavorable Outcomes, Major Bleeding, and All-Cause Mortality in Patients with Venous Thromboembolism.

PurposeThis study aimed to analyze the clinical outcomes of venous thromboembolism (VTE) patients and identify the risk factors for VTE-related unfavorable outcomes, major bleeding, and 30-day all-cause mortality.MethodsMaterials and From January 2016 to December 2020, 198 patients with confirmed VTE were enrolled. Potential risk factors for unfavorable outcomes, major bleeding, and all-cause mortality were analyzed.ResultsVTE-related unfavorable outcomes developed in 13.1%, while 30-day all-cause mortality was 8.6%. In the multivariate analysis, a pulse ≥110/min and respiratory rate ≥30/min were statistically significant predictors for VTE-related unfavorable outcomes. Diabetes was a significant risk factor for major bleeding. In addition, a history of malignancy, no anticoagulation treatment, and need for mechanical ventilation were significant predictors of all-cause mortality.ConclusionVTE-related mortality and morbidity rates remained high. In cases of tachycardia and tachypnea, early aggressive treatment is needed to prevent unfavorable outcomes. Patients with risk factors should be closely monitored.

Detection and management of bleeding in the setting of image-guided percutaneous needle biopsy.

Image-guided percutaneous needle biopsy (PNB) is an important and increasingly utilized method of minimally invasive tissue sampling for a broad variety of disease processes. While infrequent, major bleeding is a potential complication of PNB and can be life-threatening, especially when unrecognized. On the other hand, prompt recognition and treatment of major bleeding in this setting can prevent significant morbidity or mortality. It is therefore crucial for anyone performing PNB to be familiar with the diagnosis and management of bleeding complications. This article reviews the risk factors for major bleeding in the setting of PNB, the presentation and imaging findings of a spectrum of bleeding complications encountered during and following PNB, and the management of those findings based on experience at a single, high volume, biopsy center.

Ticagrelor or clopidogrel after acute coronary syndrome in the elderly: a propensity score matching analysis from 16 653 patients included in two large multinational registries

Abstract Background Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) has been suggested. Purpose We assessed the incidence of major bleeding (MB), reinfarction (REAMI), and all-cause death in elderly patients to evaluate the safety and efficacy of ticagrelor versus clopidogrel in a population at high risk of bleeding and ischemia treated with percutaneous coronary intervention (PCI). Methods RENAMI and BleeMACS, real-world registries of patients with ACS who underwent PCI and received dual antiplatelet therapy, were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor and propensity score matching (PSM) analysis performed. Statistical analysis considered two age groups (&amp;lt;75 versus ≥75 years). Endpoints were BARC 3–5 MB, REAMI and all-cause death at 1 year. Independent risk factors of MB were identified. Results The study included 16,653 patients (13,153 &amp;lt;75 and 3,500 ≥75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P&amp;lt;0.001). Using PSM, two treatment groups of 1,566 patients were included in the final analysis. Ticagrelor appeared to prevent REAMI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2–0.6; P&amp;lt;0.001) and all-cause death (HR, 0.60; 95% CI, 0.4–0.9; P=0.026) irrespective of age. In patients ≥75 years, ticagrelor increased the incidence of MB compared with clopidogrel (HR, 1.49; 95% CI, 0.70–3.0; P=0.257) without statistical significance; ticagrelor was found to significantly reduce all-cause death (HR, 0.32; 95% CI, 0.1–0.8; P=0.012) and REAMI (HR, 0.25; 95% CI, 0.1–1.1, P=0.072) without statistical significance. Multiple Cox regression revealed that age (HR, 1.03; 95% CI, 1.02–1.05; P&amp;lt;0.001) was an independent risk factor for bleeding, whereas hemoglobin level was inversely proportional to bleeding (HR, 0.80; 95% CI, 0.72–0.88; P&amp;lt;0.001). Conclusions Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients hospitalized for ACS and treated with PCI, significantly improving 1-year survival. Further studies on elderly patients are required. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Astra Zeneca

Non-vitamin K antagonist oral anticoagulants in adult congenital heart disease: a single-center study

Abstract Introduction Adults with congenital heart disease (ACHD) are at an increased risk for thromboembolic events and atrial arrhythmias are common in this population. Non-vitamin K anatagonist oral anticoagulants (NOACs) prescription is increasing, however data on efficacy and safety in ACHD is unclear, particularly in patients (P) with complex CHD. The aim of the study was to review the use of NOACs in various types of ACHD and assess its safety and efficacy. Methods Evaluation of consecutive ACHD P started on NOAC therapy from 2014 to 2020. P were followed-up for bleeding or thromboembolic events and mortality. CHA2DS2-VASc and HASBLED scores were calculated and risk factors for bleeding were identified. Results 93 ACHD P were included, mean age 52±15 years, 58% female, 44% with complex CHD (3.2% with Fontan circulation), with diagnosis of: 22.2% atrial septal defect, 20% tetralogy of Fallot, 11.1% transposition of the great arteries, 10% Ebstein's anomaly, 8.9% ventricular septal defect, 7.8% pulmonary stenosis, 5.6% ductus arteriosus, 4.4% AV septal defect, 3.4% univentricular heart, 3.4% coarctation of aorta, 2.2% supra-aortic stenosis and 1% with Uhl disease. Most P were anticoagulated with rivaroxaban (43%), followed by edoxaban (24%), apixaban (20%), and dabigatran (13%). The indications for anticoagulation were: atrial arrhythmias (81%), pulmonary embolism (PE) (6.3%), atrial thrombi (4.3%), thromboprophylaxis in Fontan circulation (3.2%), deep vein thrombosis (3.2%) and stroke (2%). 66% of P had a CHA2DS2-VASc score ≥2 and 82% HASBLED score ≤2. In a mean follow-up of 41±21 months (400.4 patient-years), there were embolic events in 2P (1 splenic infarction and 1 PE) albeit both were in the context of oral anticoagulation interruption. The cardiovascular mortality was 2% and allcause mortality 5%, however with no relation to thrombosis or bleeding events. 6 P (6.5%) suffered a minor and 3 P (3.2%) suffered a major bleeding, a median time of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. P with bleeding events showed no significant difference regarding age (55±16 vs 52±15 years, p=0.587), gender (13% female vs 5.1% male, p=0.295) or CHD type (p=0.582). 8.6% of P required dose reduction, mostly for bleeding (3.2%) or renal impairment (2.2%). Renal disease was a strong risk factor for major bleeding (HR 14.6 [95% CI 1.23–73.6], p=0.033 and multivariate analysis showed that an increased HASBLED score was an independent predictor of minor (adjusted HR 3.44 [95% CI 1.13–10.52], p=0.030) and major (adjusted HR 5.29 [95% CI 1.14–24.45], p=0.033) bleeding complications. Conclusion Anticoagulation with NOACs is a safe and effective option for selected ACHD P, although bleeding complications were not negligible, particularly in P with renal disease. Larger scale research studies are required, especially regarding complex CHD such as P with Fontan circulation. Funding Acknowledgement Type of funding sources: None.

Risk factors of recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism: from the COMMAND VTE Registry

Abstract Background/Introduction Patients with venous thromboembolism (VTE), including pulmonary embolism (PE), have a long-term risk of recurrence, and anticoagulation therapy is recommended for the prevention of recurrence. The latest 2019 European Society of Cardiology (ESC) guideline classified the risks of recurrence into low- (&amp;lt;3%/year), intermediate- (3–8%/year), and high- (&amp;gt;8%/year) risk, and recommended the extended anticoagulation therapy of indefinite duration for high-risk patients as well as intermediate-risk patients. However, extended anticoagulation therapy of indefinite duration for all of intermediate-risk patients have been a matter of active debate. Thus, additional risk assessment of recurrence in intermediate-risk patients might be clinically relevant in defining the optimal duration of anticoagulation therapy. Furthermore, bleeding risk during anticoagulation therapy should also be taken into consideration for optimal duration of anticoagulation therapy. However, there are limited data assessing the risk of recurrence as well as bleeding in patients with intermediate-risk for recurrence based on the classification in the latest 2019 ESC guideline. Purpose The current study aimed to identify the risk factors of recurrence as well as major bleeding in patients with intermediate-risk for recurrence, using a large observational database of VTE patients in Japan. Methods The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. Results In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97–14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56–7.50), while the independent risk factors for major bleeding were age ≥75 years (HR 2.04, 95% CI 1.36–3.07), men (HR 1.52, 95% CI 1.02–2.27), history of major bleeding (HR 3.48, 95% CI 1.82–6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04–6.37). Conclusions Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Research Institute for Production Development, Mitsubishi Tanabe Pharma Corporation

Catheter-directed thrombolysis for deep vein thrombosis: 2021 update.

Catheter-directed thrombolysis (CDT) has been utilized as an adjunct to anticoagulant therapy in selected patients with deep vein thrombosis (DVT) for approximately 30 years. CDT used to be limited to patients with DVT causing acute limb threat and those exhibiting failure of initial anticoagulation, but has expanded over time. Randomized trials evaluating the first-line use of CDT for proximal DVT have demonstrated that CDT does not produce a major reduction in the occurrence of post-thrombotic syndrome (PTS) and that it is poorly suited for elderly patients and those with limited thrombus extent or major risk factors for bleeding. However, CDT does offer selected patients with acute iliofemoral DVT improvement in reducing early DVT symptoms, in achieving reduction in PTS severity, and in producing an improvement in health-related quality of life (QOL). Clinical practice guidelines from medical and surgical societies are now largely aligned with the randomized trial results. This review offers the reader an update on the results of recently completed clinical trials, and additional guidance on appropriate selection of patients with DVT for catheter-directed thrombolytic therapy.

Complications after native kidney biopsy: definitive data.

To assess the risk of complications associated with native kidney biopsies. This review will highlight recent advances on the risk factors for major bleeding and risk management in patients with native kidney biopsy. Recent studies provided new important data regarding the individualization of the risk of bleeding after kidney biopsy. A new bleeding risk score was proposed as a risk stratification tool, useful for shared decision making and procedure choice. The risk of complications is low (<1%) in most patients but varies widely. Risk factors include Charlson index, frailty index, female gender, dyslipidemia, anemia, thrombocytopenia, cancer, abnormal kidney function, glomerular disease, autoimmune disease, vasculitis, hematologic disease, and thrombotic microangiopathy. A new bleeding score can help physicians and patients to assess the risk of bleeding enabling informed consent, and decide to perform it or not, and to prefer transjugular vs percutaneous route.

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Incidence of and Risk Factors for Major Hemorrhage in Patients Treated with Ibrutinib: Results from an Integrated Analysis

Incidence of and Risk Factors for Major Hemorrhage in Patients Treated with Ibrutinib: Results from an Integrated Analysis

Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial.

BackgroundThere is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation.Methods and ResultsFrom the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus‐Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m2 were associated with an increased risk of major bleeding. In contrast, 3‐month aspirin therapy with continued ticagrelor (versus 12‐month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3‐month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39–0.90; P interaction=0.74).ConclusionsLow body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk.RegistrationURL: https://www.clinicaltrials.gov/. Unique Identifier: NCT02494895.

Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT).

Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008-11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3-5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. Unique identifier NCT00811772; http://www.clinicaltrial.gov.

Early postoperative bleeding after isolated coronary bypasses: Changes over a period of 20 years-An observational study.

The objectives were to analyze the evolution of the postoperative bleeding after coronary artery bypass grafting and to determine which factors impacted on this evolution. This is a single-center retrospective study including 4590 patients undergoing coronary bypass surgery between 1995 and 2017. The study period was divided into 3 same-sized periods. We analyzed the evolution of the bleeding according to: the chest volume bleeding over the first 24hours, the severity and the rate of transfusion during the hospital stay. Intrahospital outcomes were compared between "minor" and "major" bleedings. The risk factors of major bleeding were analyzed by multiple logistic regression. The chest volume decreased particularly during the first years of the study period. Major bleedings decreased over the periods (7.3%, 4.9% and 3.8% respectively, P<0.0001), as did the rate of transfusion (26.4%, 23.5% and 19.6% respectively, P<0.0001). Major bleedings were correlated with hospital mortality (8.2% versus 1.1%, P<0.0001). The risk factors of major bleeding were the period 1 (1995 to 2003), a renal failure, a resternotomy, the EuroSCORE, the hematocrit prior to cardiopulmonary bypass and the duration of cardiopulmonary bypass. Postoperative bleeding decreased mainly in the 1990s. Progressive changes in bleeding prevention and blood recovery, surgical techniques, haemoglobin threshold for transfusion decision and practitioners' experience have contributed to these results and must be continued to optimize the postoperative outcomes.

Impact of anemia on clinical outcomes of patients with atrial fibrillation: The COOL‐AF registry

BackgroundTo determine whether anemia is an independent risk factor for ischemic stroke and major bleeding in patients with non‐valvular atrial fibrillation (NVAF).HypothesisAnemia in patients with NVAF increase risk of clinical complications related to atrial fibrillation.MethodsWe conducted a prospective multicenter registry of patients with NVAF in Thailand. Demographic data, medical history, comorbid conditions, laboratory data, and medications were collected and recorded, and patients were followed‐up every 6 months. The outcome measurements were ischemic stroke or transient ischemic attack (TIA), major bleeding, heart failure (HF), and death. All events were adjudicated by the study team. We analyzed whether anemia is a risk factor for clinical outcomes with and without adjusting for confounders.ResultsThere were a total of 1562 patients. The average age of subjects was 68.3 ± 11.5 years, and 57.7% were male. The mean hemoglobin level was 13.2 ± 1.8 g/dL. Anemia was demonstrated in 518 (33.16%) patients. The average follow‐up duration was 25.8 ± 10.5 months. The rate of ischemic stroke/TIA, major bleeding, HF, and death was 2.9%, 4.9%, 1.8%, 8.6%, and 9.2%, respectively. Anemia significantly increased the risk of these outcomes with a hazard ratio of 2.2, 3.2, 2.9, 1.9, and 2.8, respectively. Oral anticoagulants (OAC) was prescribed in 74.8%; warfarin accounts for 89.9% of OAC. After adjusting for potential confounders, anemia remained a significant predictor of major bleeding, heart failure, and death, but not for ischemic stroke/TIA.ConclusionAnemia was found to be an independent risk factor for major bleeding, heart failure, and death in patients with NVAF.

High incidence of major bleeding with off-label use of edoxaban.

In clinical practice, edoxaban is sometimes prescribed for off-label use based on the hypothesis that it is as safe and effective as warfarin. However, there is limited safety information on off-label use due to lack of clinical trial. We aimed to analyze the tolerability of off-label use of edoxaban and to identify patient characteristics associated with major bleeding as adverse effects. Patients under edoxaban treatment between January 2017 and December 2017 were enrolled in this retrospective cohort study. The incidence of major bleeding with off-label use compared with on-label use was analyzed using by log-rank test. Univariate and multivariate regression analysis were undertaken to detect independent variables with significant odds ratio that associated with major bleeding. After the exclusion criteria were applied, the patients were divided into two groups: off-label group (n = 30) and on-label group (n = 161). Incidence of major bleeding was found to be higher in the off-label group (13.3%) than in the on-label group (3.7%) (p<0.05). Multivariate adjustment showed that the off-label use or portal vein thrombosis and patients with history of major bleeding has significantly higher incidence of major bleeding. We demonstrated that off-label use of edoxaban may be a significant risk factor for major bleeding.