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

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.

Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Drug Eluting Stent ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

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 ◽  
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.

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

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.

Major Bleeding with Ibrutinib: More Than Expected

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3229-3229 ◽  
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.

scholarly journals Efficacy and Safety of Direct Oral Factor Xa Inhibitors in Patients after Bariatric Surgery

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2439-2439 ◽  
Author(s):  
Margarita Kushnir ◽  
Radhika Gali ◽  
Mariam Alexander ◽  
Henny Heisler H. Billett
Keyword(s):  
Bariatric Surgery ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Significant Difference ◽  
Recurrent Vte ◽  
Post Bariatric Surgery

Background: Over 200,000 people underwent weight loss surgery in the United States in 2017. The absorption of numerous drugs has been shown to be altered in patients after bariatric procedures, as gastrointestinal absorptive surface, food volume, and gastric pH all affect bioavailability. Dosing of warfarin, which is commonly used for the treatment of venous thromboembolism (VTE), often needs to be adjusted, based on INR, after bariatric surgery. Since direct oral anticoagulants (DOACs), which are rapidly replacing warfarin as standard anticoagulant therapy, are not monitored, there is concern regarding their efficacy and safety in patients who have had bariatric surgery, particularly rivaroxaban, which is absorbed primarily in the stomach and must be taken with food at therapeutic doses. One study found that 9 out of 9 apixaban patients (but only 2 of 7 rivaroxaban patients) had levels that fell within the expected range after bariatric surgery. Effects of bariatric surgery on DOACs may be further complicated by baseline obesity and subsequent weight loss of the patients. The goal of our current study is to determine whether DOACs are safe and effective in preventing recurrent VTE in patients who have undergone bariatric surgery. Methods: Using our institutional database, we identified all adult patients (age ≥18 years) with a history of bariatric surgery (gastric banding, sleeve gastrectomy, and Roux-en-Y gastric bypass) who were started on anticoagulation with apixaban or rivaroxaban for VTE, between July 1, 2013 and June 30, 2018. We performed retrospective chart review to obtain information on patient demographics, BMI and type of bariatric surgery. We documented clinical outcomes of recurrent VTE and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or the end of study period, June 30, 2018. VTE events were confirmed by a review of imaging studies (compression ultrasonography, ventilation/perfusions scans, and CT scans). Bleeding events were included if they met criteria for clinically relevant non-major bleeding and/or major bleeding according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Safety outcomes included major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). We also compared VTE recurrence and bleeding rates between the post-bariatric surgery patients and patients with BMI >40 from our prior study. Chi- squared tests were used to assess statistical significance of the differences in recurrent VTE and bleeding rates between anticoagulant cohorts. Results: Data on 102 patients were collected: 42 patients on apixaban and 60 patients on rivaroxaban. Our population was predominantly female (82.4%) with a mean age of 48.5 years and a median BMI of 35.7 at initiation of anticoagulation. Gastric bypass was the most common bariatric procedure (51%), followed by sleeve gastrectomy (37.3%), and gastric banding (11.8%). There were no recurrent VTE events in the apixaban cohort with a median follow-up duration of 137 days. Among patients on rivaroxaban, with a median follow-up of 232 days, there was one recurrent VTE (1.7%) in a patient with a BMI of 54 at the time of event. When we compared VTE recurrence rates of our combined DOAC cohort (apixaban + rivaroxaban) between our general morbidly obese population, from a prior study at our institution, and post-bariatric surgery patients, there was no statistically significant difference (2.0% vs. 1.0%, respectively, p=0.5). In bariatric surgery patients, one CRNMB event was recorded in apixaban group (2.4%) while 4 major bleeding events occurred on rivaroxaban (6.7%), p=0.3. There was no significant difference in the rate of composite MB and CRNMB between the general obesity and bariatric surgery patients (8.0% vs. 4.9%, respectively, p=0.3). Conclusions: In a review of post-bariatric surgery patients on anticoagulation for VTE, we found low rates of recurrent VTE for patients on DOACs. Although we had a relatively small sample size, the incidence of VTE recurrence was not higher in this cohort than was found in our previously published study of general obesity population. Prospective studies are needed to further investigate the efficacy and safety of direct oral anticoagulants in patients after bariatric surgery. Table. Disclosures Kushnir: Janssen Pharmaceuticals: Research Funding. Billett:Janssen: Research Funding.

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

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2528-2528 ◽  
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.

scholarly journals Efficacy and Safety of Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3675-3675
Author(s):  
Renata Almeida Sa ◽  
Fatimah Al-Ani ◽  
Alejandro Lazo-Langner ◽  
Martha L Louzada
Keyword(s):  
Body Weight ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Minor Bleeding ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Major Bleeding Events

Background: Obesity is a well-known risk factor for venous thromboembolism (VTE), however, obese patients are under-represented in clinical trials (1;2). Four direct oral anticoagulants (DOACs) have been approved for the treatment of acute VTE (3-6), including the direct Factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the direct thrombin inhibitor, dabigatran. Given the lack of data in this population, it is unclear if DOACs can be used safely. Objectives: To evaluate the efficacy and safety of DOACs for the treatment of VTE in obese patients. Methods: We conducted a retrospective, single-centre cohort study in London (Canada) to compare the efficacy and safety of DOACs for the treatment of acute VTE in obese patients. We screened electronic and hard copy charts of adult patients referred to our thrombosis clinic for treatment of an objectively confirmed acute VTE between January 2012 and December 2017. Patients treated with DOACs or Warfarin were selected and followed from diagnosis of the index event until cessation of anticoagulation or up to 1 year. Our study population was analyzed by BMI (BMI ≥ 30 kg/m2versus &lt; 30 kg/m2) and body weight (≥120 kg vs. &lt;120 kg). Patients were excluded if they were on anticoagulation therapy for conditions other than VTE (e.g; atrial fibrillation), cancer-associated thrombosis, or missing data. The primary outcome measure was VTE recurrence during the anticoagulation treatment period and was defined according to the ISTH criteria (7). Our secondary outcome was the occurrence of bleeding events A bleeding event is defined as: a) Major Bleeding: bleed resulting in a hemoglobin drop of &gt; 20 g/L, clinically overt and requiring more than 2 units of packed red blood cells, a hemorrhage requiring permanent cessation of anticoagulation and any retroperitoneal or intracranial hemorrhage; b) Minor Bleeding: bleed with no or little clinical significance, associated with no cost and does not require medical evaluation; and c) clinically significant non-major bleeding: does not fulfill criteria for major or minor bleeding but requires patients to be seek medical attention and/or minor procedures (8). Groups were compared using Chi-square or Fisher's exact test for categorical variables, as appropriate. The significance level was set at 0.05. Risk ratios (RR) and 95% confidence intervals (95% CI) for VTE recurrence and bleeding among DOAC groups and patients treated with Warfarin were analyzed by logistic regression. All statistical analyses were conducted using IBM SPSS Statistics version 25 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.). Results: Of 1143 potentially eligible patients, 777 fulfilled our inclusion criteria: 278 (35.8%) obese patients treated with DOACs, 266 (34.2%) non-obese patients on DOACS and 233 (30%) obese patients on Warfarin. Of the patients on DOACs, 80% (n= 436) were on rivaroxaban, while the remaining 20% were either on apixaban or edoxaban (n= 108). Among patients on DOACs VTE recurrence was observed in 2.1% (N=6) of patients with BMI ≥ 30 kg/m2 and 2.8% (N=2) of patients with 120 kg or more, with no differences in the risk of VTE recurrence (Table 1). The proportion of major bleeding events for patients on DOACs was 1.1% (N=3) for patients with BMI ≥ 30 kg/m2 and 1.4% (N=1) for patients with 120kg or more. There were no significant differences with respect to major and total bleeding risk (Table1). When comparing obese patients on DOACs vs Warfarin we did not find differences in the risk of VTE recurrence among patients with a BMI ≥ 30 kg/m2 [RR 2.59 95% IC (0.51-12.96), p= 0. 247] or body weight ≥120 kg [RR 4.33 95% IC (0.21-89.43), p= 0. 337] (Table 2). Among obese patients those treated with DOACs had a similar proportion and risk of total bleeding and major bleeding events compared to those on warfarin (Table 2). Conclusions: Our retrospective study suggests that DOACs at standard doses appear to have similar efficacy and safety in obese patients as defined herein. However, since most of our patients were treated with rivaroxaban, information on other agents is inconclusive. Information on patients with extreme body weight was limited. Disclosures Louzada: Bayer: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

scholarly journals Efficacy and Safety of Bivalirudin Versus Heparin Anticoagulation Therapy for Extracorporeal Membrane Oxygenation: Meta-Analysis

2021 ◽  
Author(s):  
Jie Gu ◽  
Hongjie Yu ◽  
Dang Lin
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Hospital Mortality ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Minor Bleeding ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Heparin Induced Thrombocytopenia ◽  
Membrane Oxygenation ◽  
Major Bleeding Events

Abstract Background We aimed to compare the efficacy and safety of bivalirudin versus heparin as the anticoagulant in patients undergoing Extracorporeal Membrane Oxygenation (ECMO). Methods We conducted a search in PubMed, Embase and the Cochrane Library for all the studies in which bivalirudin was compared to heparin as the anticoagulant for ECMO. Efficacy outcomes were defined as the time to reach therapeutic levels, time within therapeutic range (TTR), thrombotic events, circuit thrombosis, circuit exchanges. Safety outcomes were reported as Heparin-Induced Thrombocytopenia (HIT), major bleeding events, minor bleeding events. Other outcomes included hospital length of stay (LOS), ICU LOS, mortality, 30-day mortality and in-hospital mortality. Results Ten studies were included, involving 1091 patients (Bivalirudin was administered in 405 patients while 686 patients were treated with heparin). A significant reduction in thrombotic events [OR 0.51, 95%CI 0.36,0.73, p=0.0002, I2=0%], major bleeding events [OR 0.31, 95%CI 0.10,0.92, p=0.04, I2=75%] and in-hospital mortality [OR 0.63, 95%CI 0.44,0.89, p=0.009, I2=0%] treated with bivalirudin were found compared with heparin. There were no significant differences between groups regarding the time to reach therapeutic levels[MD 3.53, 95%CI -4.02,11.09, p=0.36, I2=49%], TTR[MD 8.64, 95%CI -1.72,18.65, p=0.10, I2=77%], circuit exchanges[OR 0.92, 95%CI 0.27,3.12, p=0.90, I2=38%], Heparin-Induced Thrombocytopenia (HIT)[OR 0.25, 95%CI 0.02,2.52, p=0.24, I2=0%], minor bleeding events[OR 0.93, 95%CI 0.38,2.29, p=0.87, I2=0%], hospital LOS[MD -2.93, 95%CI -9.01,3.15, p=0.34, I2=45%], ICU LOS[MD -4.22, 95%CI -10.07,1.62, p=0.16, I2=0%], mortality[OR 1.84, 95%CI 0.58,5.85, p=0.30, I2=60%] and 30-day mortality[OR 0.75, 95%CI 0.38,1.48, p=0.41, I2=0%]. The benefit of bivalirudin over heparin was not significant for patients undergoing ECMO for major bleeding events while ruling out the Rivosecchi’s study (OR 0.44, 95%CI 0.71-1.14). Subgroup analysis by patient’s type revealed that studies in children generated lower rate of thrombotic events and major bleeding events compared with adults. Conclusion Our meta-analysis suggests that bivalirudin use as the anticoagulant for ECMO are associated with lower thrombotic events, major bleeding events and in-hospital mortality. Meanwhile, the differences are more pronounced in children than adults. However, the results should be interpreted with caution and further larger, randomized trials are needed to confirm the results.

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

2019 ◽  
Vol 119 (09) ◽  
pp. 1498-1507 ◽  
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.

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

2017 ◽  
Vol 20 (1) ◽  
pp. 365 ◽  
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.

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