Aspirin Thromboprophylaxis in Joint Replacement Surgery

Introduction. Total knee replacement (TKR) and total hip replacement (THA) surgeries have historically been felt to carry a high risk of post-operative venous thromboembolism (VTE) events thereby warranting anticoagulant prophylaxis. This risk however was based on composite endpoints in which asymptomatic DVT on venography, as opposed to symptomatic VTE or VTE-related mortality, constituted the majority of the events. Furthermore, current day orthopedic practices have likely led to a reduction in risk of VTE, thought to be 3-5% in the absence of prophylaxis. While the American College of Chest Physicians (ACCP) guidelines recommend the use of an anticoagulant for prophylaxis for all patients undergoing TKR and THR over aspirin, American Academy of Orthopaedic Surgeons (AAOS) guidelines classify patients without a prior history of VTE, and those not meeting their high risk criteria (significant cardiovascular disease; BMI > 40; smoking + DM + BMI > 35; and recent cancer) as low-risk; aspirin (325 mg twice daily) is a recommended alternative for post-operative VTE prophylaxis in these patients. As a result, many orthopedic surgeons in the US use aspirin for patients without major risk factors for VTE other than the surgery itself, accounting for over 40% joint replacement surgery cases in the US. The risk of symptomatic VTE in this patient population outside of small and primarily retrospective studies remains unknown. We conducted a prospective cohort study of patients receiving aspirin thromboprophylaxis following TKR and THR surgery at a large orthopedic specialty hospital to assess the risk of clinically symptomatic VTE and bleeding events. This is a preliminary analysis of planned total accrual of 500 subjects (assuming 2% VTE event rate in aspirin-treated patients, as compared to 1% in anticoagulant-treated, with alpha and beta error levels of 5% and 50%, respectively, and accounting for attrition rate of at least 10%). Methods. All TKR and THR patients prescribed aspirin for VTE prophylaxis by the surgical team and not on any anticoagulant medications were eligible for the study. Study subjects were identified and consented post-operatively prior to their hospital discharge. Enrolled subjects were followed for symptomatic VTE and bleeding events during their hospitalization, and then contacted at 30 and 90 days postoperatively for a telephone survey. Symptomatic VTE and bleeding events were captured using a questionnaire and outside records obtained to confirm VTE or major bleeding events. Three-month risk of symptomatic VTE and major bleeding events associated with aspirin thromboprophylaxis were estimated. Results. A total of 300 patients, 199 TKR and 101 THR, have been enrolled in this ongoing study so far. Table 1 shows the baseline characteristics of the patients. A total of 6 symptomatic VTE (4 pulmonary emboli, 1 proximal deep vein thrombosis (DVT) and 1 isolated-distal DVT) occurred during the follow up period. (3-month post-op VTE event rate of 2%). 3 events were diagnosed during hospitalization, whereas the remaining 3 occurred following hospital discharge (within 7-10 days). Bruising was a common side effect affecting nearly 3% of the patients, but major bleeding events were rare, only 1 major upper gastrointestinal bleeding, giving a 3-month risk of 0.33%. There were no surgical bleeds reported. Conclusions. In this single-center prospective cohort study of TKR and THR patients considered to be at lower risk for VTE, the use of aspirin for thromboprophylaxis was associated with a 2% symptomatic VTE event rate over three months of follow up with minimal bleeding risk. This result, together with those of the EPCATII study from Canada showing that low-dose aspirin was as effective (~0.7% event rate) following 5 days of rivaroxaban following TKR and THR in lower risk patients, argues for a large randomized trial evaluating aspirin as monotherapy for VTE prophylaxis in such patients. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Concurrent Use of Chinese Herbal Medicine and Anticoagulants May Reduce Major Bleeding Events

10.21203/rs.3.rs-683341/v1 ◽

2021 ◽

Author(s):

Shuo-Min Hsu ◽

Hung-Jen Lin ◽

Yi-Wei Kao ◽

Te-Mao Li ◽

Ben-Chang Shia ◽

...

Keyword(s):

Herbal Medicine ◽

Chinese Herbal Medicine ◽

Major Bleeding ◽

Lower Risk ◽

Panax Notoginseng ◽

Research Database ◽

Bleeding Events ◽

Chinese Herbal ◽

Concurrent Use ◽

Major Bleeding Events

Abstract Background: This retrospective cohort study investigated the risk of major bleeding events during the concurrent use of Chinese herbal medicine (CHM) and anticoagulants in clinical practice. Methods: A total of 4,470 patients receiving anticoagulant drugs were selected from Taiwan’s National Health Insurance Research Database (NHIRD). Half (n=2,235) were also using CHMs (CHM cohort); the other half were not (non-CHM cohort). Each cohort was matched 1:1 using the propensity score. Chi-square testing and the Student’s t-test were used to examine differences between two cohorts. Cox proportional hazard regression analysis assessed the risks for major bleeding events in each cohort, as well as bleeding risks associated with specific CHM formulas and herbs. Cumulative incidence curves for major bleeding events were calculated using Kaplan-Meier analysis. Results: Compared with the non-CHM cohort, the CHM cohort had a lower risk of overall bleeding events (p < 0.001) including hemorrhagic stroke (p = 0.008), gastrointestinal (GI) bleeding (p < 0.001), urogenital bleeding (p ≤ 0.001) and nasal/ear/eye bleeding (p = 0.004). Single herbs, such as Glycyrrhiza uralensis et Rhizoma, Panax notoginseng, Panax ginseng, Platycodon grandiflorum, Eucommia ulmoides Oliver and formulas, such as Shu Jing Huo Xue Tang, Shao Yao Gan Cao Tang and Ji Sheng Shen Qi Wan were associated with a lower risk of major bleeding events. Conclusions: Using CHMs with anticoagulants appeared to decrease the risk of major bleeding. Further investigations are needed to determine whether CHM can maintain the therapeutic efficacy of anticoagulants while simultaneously reducing potential side effects.Trial registration: Not applicable.

Download Full-text

Abstract 17152: Frequency and Management of Major Bleeding in Atrial Fibrillation Patients Treated With Warfarin and Non-vitamin K Oral Anticoagulants in Community Practice: Results From the ORBIT-AF II Registry

Circulation ◽

10.1161/circ.132.suppl_3.17152 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Benjamin A Steinberg ◽

DaJuanicia N Simon ◽

Laine Thomas ◽

Jack Ansell ◽

Gregg C Fonarow ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Recurrent Bleeding ◽

Bleeding Events ◽

Reversal Agents ◽

Major Bleeding Events

Background: Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice. Methods: We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days). Results: Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%. Conclusions: Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.

Download Full-text

P4742Evaluation of the HAS-BLED, ATRIA and ORBIT bleeding risk scores in newly diagnosed non-valvular atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehz745.1118 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Bergamaschi ◽

A Stefanizzi ◽

M Coriano ◽

P Paolisso ◽

I Magnani ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Independent Predictor ◽

Bleeding Risk ◽

Risk Scores ◽

Newly Diagnosed ◽

Bleeding Events ◽

Hemorrhagic Events ◽

Major Bleeding Events

Abstract Background Several risk scores have been proposed to assess the bleeding risk in patients with Atrial Fibrillation. Purpose To compare the efficacy of HAS-BLED, ATRIA and ORBIT scores to predict major bleedings in newly diagnosed non-valvular AF (NV-AF) treated with vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Methods We analyzed all consecutive patients with AF at our outpatient clinic from January to December 2017. Only those with new diagnosed NV-AF starting new anticoagulant therapy were enrolled. Major hemorrhagic events were defined according to the ISTH definition in non-surgical patients. Results Out of the 820 patients admitted with AF, 305 were newly diagnosed with NV-AF starting oral anticoagulation. Overall, 51.3% were male with a mean age of 72.6±13.7 years. Thirty-six patients (11.8%) started VKAs whereas 269 (88.2%) patients were treated with NOACs. The median follow-up time was 10.4±3.4 months. During follow-up, 123 (32.2%) bleeding events were recorded, 21 (17,1%) in the VKA group and 102 (82,9%) in the NOAC group. Eleven (2.9%) major bleeding events occurred: 5 (45.5%) in the VKA group and 6 (54.5%) in the NOAC group. Overall, patients with major hemorrhagic events showed a mean value of the scores significantly higher when compared to patients without such bleeding complications (HASBLED 3.4 vs 2.4 p=0.007; ATRIA 5.6 vs 2.4 p<0.001; ORBIT 3.6 vs 1.8 p<0,001). Conversely, when analyzing the VKA subgroup, only the ATRIA score was significantly higher in patients with major adverse events (7.4 vs 3.5 p<0.001; HAS-BLED: 4.4 vs 3.6 p=0.27; ORBIT 4.4 vs 2.9 p=0.13). An ATRIA score ≥4 identified patients at high risk of bleeding (29.4% vs. 0% events. respectively, p=0.04). In the NOAC group, patients with major bleeding events had higher mean values of ATRIA (4.0 vs 2.3 p=0.02) and ORBIT (2.8 vs 1.6 p=0,04) but not the HAS-BLED (2.5 vs 2.3 p=0.57) scores. Similarly, patients on NOACs with an ATRIA score ≥4 had higher rates of major bleedings (8.1% vs. 1.6% p=0,02). Comparing the single elements of the ATRIA score, only glomerular filtration rate <30 ml/min/1.73 mq was associated with major bleedings in the VKA group (p<0.001) whereas, in the NOAC group, anemia was strongly associated with bleeding events (p=0,02). In fact, multivariate analysis in the NOAC group showed that hemoglobin level at admission was an independent predictor for major bleeding events (OR 0.41, 95% CI 0.23–0.75, P=0.003). Conversely, in the VKA group, baseline creatinine level was an independent predictor for these events (OR 12.76, 95% CI 1.6–101.7, P=0.016). Conclusions The ATRIA score showed the best efficacy in predicting major bleeding events. Hemoglobin and creatinine levels at admission were independent predictors for major hemorrhagic events in the NOAC and in the VKA groups, respectively. The latter finding might be helpful in stratifying the hemorrhagic risk at the beginning of treatment.

Download Full-text

Primary Venous Thromboembolism Prophylaxis in Patients with Solid Tumors Receiving Chemotherapy: A Meta-Analysis

Blood ◽

10.1182/blood.v120.21.1157.1157 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1157-1157

Author(s):

Minh Phan ◽

Sonia John ◽

Ana Isabel Casanegra ◽

Alfonso Tafur

Keyword(s):

Venous Thromboembolism ◽

Solid Tumors ◽

Major Bleeding ◽

Meta Analysis ◽

Mortality Data ◽

Significant Heterogeneity ◽

Bleeding Events ◽

Vte Prophylaxis ◽

Major Bleeding Events ◽

Pharmacological Thromboprophylaxis

Abstract Abstract 1157 Background: Venous thromboembolism [VTE] is the second highest cause of mortality among patients with cancer. However, pharmacological thromboprophylaxis for patients with solid tumor is only recommended during hospitalization. Primary outpatient thromboprophylaxis is not a widely accepted practice. Objective: Determine safety and efficacy of outpatient primary VTE prophylaxis in patients with solid tumors. Data sources: A systematic review was conducted using MEDLINE and EMBASE up to June 2012. Key search words included venous thromboembolism, malignancy, anticoagulants, and chemotherapy. Studies were considered for our meta-analysis if they included outpatient primary pharmacological thromboprophylaxis in adult patients with active solid cancer. All the information was independently reviewed by 2 of the authors [MP, SJ] and a third reviewer resolved discrepancies. The measure of association was calculated with R (R: A Language and Environment for Statistical, R Development Core Team, www.R-project.org), R META package (Version 0.8–2, Author: Guido Schwarzer). The Q statistic was calculated and a formal test of homogeneity was conducted. Random-effects model was preferred in case of heterogeneity. Results: A total of 1371 abstracts were reviewed and 29 manuscripts were fully abstracted. Eight randomized controlled trials including 6706 patients were analyzed. There were less VTE events with outpatient prophylaxis: odds ratio [OR] of 0.53 (95% CI, 0.40–0.70). Six studies used low or ultra-low molecular weight heparin and two studies used warfarin. In the subgroup analysis of heparin based primary prophylaxis, there was a significant reduction in VTE events [OR 0.47, 95% CI, 0.34–0.64], no significant heterogeneity [FIG 1]. In addition, there was no difference in major bleeding events between groups [OR 1.48, 95% CI, 0.89–2.46]. Five studies reported mortality data; there was significant heterogeneity between studies. Conclusions: Heparin based outpatient VTE prophylaxis in patients with solid tumors reduced by half the risk of VTE with no significant differences in major bleeding events. The current publications do not allow a meaningful grouped analysis of survival data, improved patient selection is necessary in order to adequately target VTE prevention strategies. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Major Bleeding with Ibrutinib: More Than Expected

Blood ◽

10.1182/blood.v128.22.3229.3229 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3229-3229 ◽

Cited By ~ 11

Author(s):

Paul R Kunk ◽

Joesph Mock ◽

Michael E. Devitt ◽

Surabhi Palkimas ◽

Jeremy Sen ◽

...

Keyword(s):

Adverse Events ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Event ◽

Lymphocytic Leukemia ◽

Significant Activity ◽

University Of Virginia ◽

Bleeding Events ◽

Major Bleeding Events

Abstract Introduction: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has significant activity in treating lymphoma. While approved for patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), its activity in other lymphomas and solid tumors is under investigation and its use is increasing dramatically. Overall it is well tolerated compared to chemotherapy, but bleeding has emerged as a common adverse event with rates as high as 50% and major bleeding around 3% (Jones, abstract #1990, 2014 ASH Annual Meeting). As the use of ibrutinib increases outside of a clinical trial setting, the rate of major bleeding is likely to rise. Methods: To better understand the risk of bleeding in ibrutinib treated patients, we reviewed all patients at the University of Virginia and satellite clinics who were treated with ibrutinib between January 2012 and May 2016. Patients were required to be treated for at least 1 month with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, ibrutinib indication and dose, length of treatment, concurrent medications, blood tests and bleeding events. All forms of anti-platelets and anticoagulants drugs, as well as medications interacting with cytochrome P450 3A4 (3A4), which metabolizes ibrutinib, were recorded. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators. Results: Eighty-nine patients were identified. Eighteen patients were excluded for insufficient follow up leaving 71 patients for analysis. Median age was 73 years old (44-92) with 74% male. The most common indications for treatment were CLL (65%) and MCL (27%). Most patients were treated with either 420mg (64%) or 560mg (21%). Median length of time on ibrutinib was 412 days, most with ongoing use at time of data collection. Seventy percent of patients were also treated with an anti-platelet medication, mostly aspirin for CAD with several patients on multiple anti-platelet medications. Seventeen percent were treated with an anti-coagulant, mostly apixaban for atrial fibrillation. Thirteen percent of patients (9/71) were treated with combined anti-platelet and anti-coagulant medications. Ten percent of patients were treated with a medication that has a moderate or strong interaction with 3A4. Bleeding of any grade occurred in 56% of patients, mostly bruising and epistaxis. Major bleeding, defined as grade 3 or higher, occurred in 18% of patients. Three patients developed major bleeding after an invasive procedure without ibrutinib being held. One patient died as a result of peri-procedural bleeding. Of the 9 patients treated with combined anti-platelet and anti-coagulant therapy, 78% suffered a major bleeding event. Of the ten patients on ibrutinib alone, without concurrent use of an anti-platelet, anti-coagulant or 3A4 drug interaction, no major bleeding events occurred. Conclusion: In this study examining real world use of ibrutinib, the rates of major bleeding are higher than previously reported. Most patients who suffered major bleeding were also treated with an anti-coagulant and/or anti-platelet medication. As the use of ibrutinib increases outside of clinical trials, a careful review of medications should be performed in addition to adherence to perioperative drug withholding guidelines. Patients requiring anti-coagulant and/or anti-platelet medications while on ibrutinib need careful consideration of the risks and benefits given the higher incidence of bleeding in this population. Table 1 Table 1. Disclosures Portell: AbbVie: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Acerta: Research Funding. Williams:Janssen and Pharmacyclics: Research Funding; University of Virginia: Employment.

Download Full-text

Case Fatality Rate of Recurrent Venous Thromboembolism and Major Bleeding Events Among Patients Treated for Cancer-Associated Venous Thromboembolism: A Systematic Review

Blood ◽

10.1182/blood-2018-99-110271 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2528-2528 ◽

Cited By ~ 2

Author(s):

Alym Abdulla ◽

Wendy Davis ◽

Namali Ratnaweera ◽

Brooke Scott ◽

Agnes Yuet Ying Lee

Keyword(s):

Major Bleeding ◽

Research Funding ◽

Case Fatality Rate ◽

Case Fatality ◽

Controlled Trials ◽

Bleeding Events ◽

Patients With Cancer ◽

Recurrent Vte ◽

Major Bleeding Events

Abstract Background Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. Despite therapeutic anticoagulation, the risks of recurrent VTE and major bleeding are approximately 10% and 5%, respectively, during the first 6 months of treatment. Overall mortality ranges from 25% to 40%, depending on the study population. Knowing the case fatality rates of these outcomes is also important for weighing the relative risks and benefits of anticoagulation in patients with cancer-associated VTE but these rates have not been reported previously. Objective To determine the incidence of recurrent VTE and major bleeding events and to calculate the case fatality rates of these outcomes in patients undergoing anticoagulation for cancer-associated VTE. Methods An electronic search of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials from January 1980 to May 2018 was performed. English language publications (observational studies and randomized controlled trials [RCTs]) that reported on patients with active cancer and VTE who received anticoagulation with low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC) for at least 3 months were retrieved for review. In addition, a hand search of references of review articles was done to complement the electronic literature search. Studies that provided information on recurrent VTE, major bleeding events, mortality, and causes of death were included in analyses. Retrospective studies and prospective cohorts with fewer than 50 patients were excluded. Two reviewers independently screened for study eligibility and extracted data onto standardized forms. Study outcomes were recurrent VTE, major bleeding and death. Pooled proportions with 95% confidence intervals (CI) were calculated according to anticoagulant treatment and study design. Results The search identified 7327 studies of which 29 studies (15 prospective cohort studies and 14 randomized controlled trials) were included. Data from 8000 cancer patients followed for a total of 4786 patient-years (range 3 to 36 months) were summarized. The rate of recurrent VTE and fatal recurrent VTE were 15.7% (95% CI, 14.4% to 17.1%) and 2.5% (95% CI, 2.0% to 3.0%) per patient-year of follow-up, respectively, with a case fatality rate of 15.8% (95% CI, 12.7% to 18.8%). A sub-analysis revealed case fatality rates for recurrent VTE to be 16.3% (95% CI, 12.2% to 20.4%) for LMWH, 20.4% (95% CI, 14.0% to 26.8%) for VKA, and 10.8% (95% CI, 3.2% to 18.3%) for DOAC therapies. The rate of major bleeding and fatal major bleeding events were 6.4% (95% CI, 5.5% to 7.3%) and 1.2% (95% CI, 0.8% to 1.6%) per patient-year of follow-up, respectively, with a case fatality rate of 12.3% (95% CI, 8.7% to 15.9%). A sub-analysis revealed case fatality rates for major bleeding events to be 14.9% (95% CI, 9.6% to 20.2%), 27.9% (95% CI, 14.5% to 41.3%), and 1.9% (95% CI, 0% to 5.5%) for LMWH, VKA, and DOAC therapies, respectively. Among RCTs, case fatality for recurrent VTE was 17.3% (95% CI, 13.5% to 21.2%) and for major bleeding was 10.8% (95% CI, 3.2% to 18.3%). Among prospective cohort studies, respective case fatality rates were 12.8% (95% CI, 8.0% to 17.5%) and 15.3% (95% CI, 8.6% to 22.0%). Studies were heterogeneous in the duration of follow up and their reporting of the causes of death and definition of fatal PE. Conclusion The incidences of recurrent VTE and major bleed events are high in patients with cancer-associated VTE on anticoagulant therapy. Case fatality from recurrent thrombosis is higher than the case fatality from major bleeding. Differences among various anticoagulants likely reflect patient selection bias and heterogeneity of studies. Disclosures Lee: BMS: Research Funding; Bayer: Consultancy, Honoraria; LEO Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Servier: Honoraria.

Download Full-text

Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry

Thrombosis and Haemostasis ◽

10.1055/s-0039-1692425 ◽

2019 ◽

Vol 119 (09) ◽

pp. 1498-1507 ◽

Cited By ~ 8

Author(s):

Kitae Kim ◽

Yugo Yamashita ◽

Takeshi Morimoto ◽

Takeshi Kitai ◽

Takafumi Yamane ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Acute Phase ◽

Major Bleeding ◽

Anticoagulation Therapy ◽

Bleeding Events ◽

Increased Risk ◽

Major Bleeding Events ◽

Active Cancer

Background There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients. Patients and Methods The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153). Results During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23–4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51–3.59), anemia (HR, 1.75, 95% CI, 1.27–2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27–3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22–2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model. Conclusion Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

Download Full-text

Cilostazol for Chinese Patients with Aspirin Intolerance after Coronary Drug-Eluting Stent Implantation

Thrombosis and Haemostasis ◽

10.1055/s-0040-1709520 ◽

2020 ◽

Vol 120 (05) ◽

pp. 857-865

Author(s):

Chunfeng Dai ◽

Zhangwei Chen ◽

Jiayu Fu ◽

Juying Qian ◽

Junbo Ge

Keyword(s):

Major Bleeding ◽

Large Scale ◽

Chinese Patients ◽

Drug Eluting Stent ◽

Efficacy And Safety ◽

Bleeding Events ◽

Drug Eluting ◽

Aspirin Intolerance ◽

Major Bleeding Events

Abstract Background Cilostazol-based dual antiplatelet therapy (DAPT) is widely used in patients with aspirin intolerance after coronary drug-eluting stent (DES) implantation in China. However, this empirical strategy is not recommended or even mentioned in Chinese or international guidelines due to a lack of evidence from large-scale studies. We aimed to explore the efficacy and safety of cilostazol-based DAPT in this special population. Methods In this cohort study, patients were grouped according to the DAPT strategy that they received after coronary DES implantation. The primary efficacy endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs). Angiographic follow-up and major bleeding events were also recorded. Results A total of 918 patients receiving cilostazol-based DAPT due to aspirin intolerance were enrolled, matched with 918 patients receiving aspirin-based DAPT. After 15-month prospective follow-up, the cilostazol group had lower risk of MACCE (5.1% vs. 7.6%, propensity score adjusted hazard ratio = 0.671 [95% confidence interval 0.462–0.974], p = 0.036) compared with the aspirin group. Lower rate of coronary lesion progression was also found through follow-up angiography in the cilostazol group (17.4% vs. 23.6%, p = 0.022), especially in nontarget lesions (12.1% vs. 17.6%, p = 0.019). The two groups had the same risk of major bleeding events (0.8% vs. 0.4%, p = 0.364). Conclusion In the current study, cilostazol is a good substitute for aspirin in patients who have aspirin intolerance but need DAPT after coronary DES implantation in China. However, large-scale randomized controlled trials were still required to further confirm its efficacy and safety.

Download Full-text

Assessment of Predicted Rate and Associated Factors of Dabigatran-induced Bleeding Events in Malaysian Patients with Non-Valvular Atrial Fibrillation

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3tp9q ◽

2017 ◽

Vol 20 (1) ◽

pp. 365 ◽

Cited By ~ 1

Author(s):

Semira Abdi Beshir ◽

Lok Bin Yap ◽

Szyuin Sim ◽

Kok Han Chee ◽

Yoke Lin Lo

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Congestive Heart Failure ◽

Major Bleeding ◽

Bleeding Event ◽

Minor Bleeding ◽

Bleeding Events ◽

Laboratory Test Results ◽

Major Bleeding Events

Purpose: To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy. Methods: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated. Results: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events. Conclusions: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Download Full-text