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.

scholarly journals 478 Clinical outcomes of patients at very high stroke risk undergoing watchman implantation

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Michele Magnocavallo ◽  
Domenico Giovanni Della Rocca ◽  
Carlo Lavalle ◽  
Gianni Carola ◽  
Sa Mohanty ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Stroke Risk ◽  
Bleeding Event ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Related Complication ◽  
Watchman Device ◽  
Major Bleeding Events ◽  
Very High

Abstract Aims Left atrial appendage occlusion (LAAO) with the Watchman device is an effective alternative to oral anticoagulation in patients with non-valvular atrial fibrillation at high thromboembolic risk. We sought to evaluate the safety and effectiveness of LAAO for stroke and bleeding prevention in patients at very high stroke risk. Methods and results Data were extracted from a prospective database of 488 AF patients who underwent LAA closure with a Watchman device. Periprocedural complications, thromboembolic (TE), and bleeding event rates among patients with a CHA2DS2-VASc ≥ 5 were reported. Predicted annual rates of TE or major bleeding events were compared to the annualized observed risk of the population. Overall, 209 patients with a CHA2DS2-VASc ≥5 (CHA2DS2-VASc: 6.0 ± 1.0; HAS-BLED: 3.7 ± 1.1) were included in the study. The mean age was 78 ± 6 years and 52.2% (n = 109) were males. Watchman implantation was successful in all patients. Overall procedure-related complication rate was 3.3% (n = 7). Two major complications were observed (1.0%): one pericardial tamponade requiring surgery and one major bleeding event at 3 days post-procedure. The incidence of minor complications was 2.3% (n = 5). Specifically, two patients experienced a pericardial effusion that required drainage and three had a groin hematoma. During a mean follow-up duration of 12 ± 5 months (193 pt/years), six TE events (2.9%/annualized rate: 3.1%) were documented after a median of 6.3 months (IQR: 2.2–9.6). Based on the estimated annual TE risk according to the CHA2DS2-VASc score (8.5%), the % risk reduction after LAAO was 63.5%. Four major bleeding events [1.9% (median time to event: 2.1 months; IQR: 1.0–3.4)] and five minor bleeding events occurred (2.5%) during follow-up. Compared to the expected rate of bleeding events as assessed by the HAS-BLED of the population (8.03%), LAAO led to a 42% reduction of bleeding risk. Conclusions In a population at very high TE risk, LAAO with the Watchman device was a safe and effective approach, and led to a 63.5% of stroke risk.

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.

P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ishigami ◽  
Y Aono ◽  
S Ikeda ◽  
K Doi ◽  
Y An ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Platelet Count ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Bleeding Events ◽  
Major Bleeding Event ◽  
Entire Cohort ◽  
Severe Group ◽  
The Mean

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p<0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p<0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p<0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p<0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

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.

Abstract 12014: Modified HASBLED Bleeding Risk Score in Dialysis Patients With Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Michele Murphy ◽  
William Maddox ◽  
Stan Nahman ◽  
Matthew Diamond ◽  
Robert Sorrentino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Failure ◽  
Liver Function ◽  
Renal Disease ◽  
Risk Score ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Major Bleeding Events

Introduction: Hemodialysis patients (HD pts) with atrial fibrillation (AF) have increased risk of stroke. The HASBLED (Hypertension (HTN), Abnl Renal/Liver Function, Stroke, Bleeding Hx, Labile INR, Elderly, Drugs/Alcohol) risk score predicts bleeding in the general AF population. It is unknown whether the HASBLED score can be applied to HD pts who are at additional bleeding risk due to uremic platelet dysfunction and the regular use of heparin. Hypothesis: To address this question, we queried the United States Renal Data System (USRDS) for bleeding events in HD pts with AF, and correlated those events with a modified HASBLED (mHASBLED) score. Methods: All incident HD pts with AF from the USRDS for 2006-2010 were queried for major bleeding events and mHASBLED parameters using ICD-9 diagnosis codes and data from CMS form 2728. For mHASBLED, the HTN parameter was defined as "HTN as the cause of renal failure", and labile INR as > 16 INRs/yr, but all other parameters could be derived from the dataset. Logistic regression (LR) analysis was used to estimate the odds ratio (OR) for the mHASBLED score to predict major bleeding events. Results: 74,631 HD pts had AF, and 9.8% had a major bleeding event (GI bleeding and hemorrhagic stroke). By univariate analysis, those who bled were more likely to be elderly, have an underlying cause of renal disease due to HTN, prior bleeding event, hepatitis C, labile INR, and be on oral anticoagulants. By LR, variables with the greatest impact on bleeding were HTN as a cause of underlying renal disease, prior bleeding history, and labile INR (OR of 1.10, 2.20 and 2.24, respectively). The OR for bleeding events increased by 1.28 for each unit increase in mHASBLED. Older age, prior stroke, abnormal renal or liver function, and drug use had the least effect. Note that the lowest possible score in this cohort is 1, given that all patients had renal failure. Conclusions: In HD pts with AF, the mHASBLED predicts major bleeding events. The universal presence of renal disease, and the lack of specific clinical data from the USRDS may limit the clinical precision of a given score, however mHASBLED may remain a useful indicator of bleeding risk in this population.

Novel bleeding prediction model in atrial fibrillation patients on new oral anticoagulants

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319702
Author(s):  
Ofra Barnett-Griness ◽  
Nili Stein ◽  
Antonio Kotler ◽  
Walid Saliba ◽  
Naomi Gronich
Keyword(s):  
Atrial Fibrillation ◽  
Health Services ◽  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Bleeding Event ◽  
New Oral Anticoagulants ◽  
Selection Algorithm ◽  
Bleeding Events ◽  
Major Bleeding Events

ObjectiveClinical models such as the HAS-BLED (standing for Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage) were developed to predict risk of major bleeding on vitamin K antagonists/antiplatelet therapy. We aimed to develop a model that will improve the ability to predict major bleeding events in patients with non-valvular atrial fibrillation (AF) treated with new oral anticoagulants (NOACs).MethodsClalit Health Services is the largest of four integrated healthcare organisations in Israel, which insures 4.7 million patients (53% of the population). We identified in Clalit Health Services all patients with AF, new users of an NOAC (2013–2017), and followed them until first occurrence of a major bleeding event, death, switch to another oral anticoagulant, 30 days after discontinuation of NOAC or end of follow-up (31 December 2019). Importance of the candidate model variables was estimated by inclusion frequencies across forward selection algorithm applied to 50 bootstrap samples. Then, backward selection algorithm using the modified Bayesian Information Criterion for competing risks was applied to select predictors for the final model.Results47 623 patients with AF prescribed NOAC were studied. 28 055 patients with AF, initiators of apixaban (mean age 78.7, SD 9.0), were included in the first phase and had 662 major bleeding events. Nine variables were selected for inclusion in a final points-based risk-scoring system: male sex, anaemia, thrombocytopaenia (<99×103/µL), concurrent antiplatelet therapy, hypertension, prior major bleeding, risk factors for a fall, low cholesterol level and low estimated glomerular filtration rate, with apparent area-under-curve (AUC) of 0.6546. Applicability of the model was then shown for 14 118 and 5450 patients with AF, initiators of dabigatran and rivaroxaban, where the score achieved c indices of 0.62 and 0.61, respectively.ConclusionsWe present a novel and simple risk score for prediction of major bleeding in patients with non-valvular AF treated with NOACs. Validation in additional cohorts is warranted.

Randomized, Parallel Group, Multicenter, Multinational Study Evaluating Safety of DU-176b Compared with Warfarin in Subjects with Non-Valvular Atrial Fibrillation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 33-33 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Stuart J. Connolly ◽  
Satoshi Kunitada ◽  
James Jin ◽  
Indravadan Patel
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Phase Iii ◽  
Fixed Dose ◽  
Bleeding Events ◽  
Treatment Groups ◽  
Parallel Group ◽  
Elevated Liver Enzymes ◽  
Major Bleeding Events

Abstract Introduction : The primary objective of this phase II study was to assess the safety of different dose regimens of DU-176b, an oral direct factor Xa inhibitor, in patients with non-valvular atrial fibrillation (AF). Methods : This was a randomized, parallel group, multicenter, multinational, double-blind DU-176b and open-label warfarin safety study in patients with AF (CHADS2 index ≥ 2). Patients were randomly assigned to receive either one of four fixed dose regimens of DU-176b (30 mg qd, 30 mg bid, 60 mg qd or 60 mg bid) or warfarin dose-adjusted to a target international normalized ratio (INR) of 2.0–3.0. for 12 weeks. Investigators, sponsor and study subjects were blinded to DU-176b dose but not to the identity of DU-176b vs. warfarin. Investigators adjusted warfarin doses based on INR values obtained in local laboratories. The INR was determined weekly for 4 weeks and every two weeks thereafter. The primary outcomes were the occurrence of centrally adjudicated major and/or clinically relevant non-major bleeding event, and elevated liver enzymes and/or bilirubin. Secondary outcomes included major adverse cardiovascular events (MACE), a composite of stroke, systemic embolism, acute myocardial infarction, hospitalizations due to cardiovascular condition or cardiovascular death, as well as all other adverse events, including all bleeding events. Results : A total of 1,146 patients were randomized. There were no clinically relevant differences between treatment groups with respect to the demographic data and baseline characteristics. Mean age was 65±8.7 years, 63.3% of patients had a CHADS2 index of 2 and 64.40% were warfarin naïve. The DU-176b 60 mg bid treatment arm was prematurely terminated during the study based on a recommendation by the Independent Data Monitoring Committee (DMC). A total of 180 patients were randomized to this group at the time. The incidence of major and clinically relevant non-major bleeding events was significantly higher in both the DU-176b 60 mg bid and 30 mg bid groups than in those given warfarin. The incidence of major and clinically relevant non-major bleeding events in the DU-176b 30 mg qd and 60 mg qd groups was similar to that in warfarin-treated patients. The time in therapeutic range (TTR) for warfarin-experienced patients was 50.1% and for warfarin naïve patients was 41.8%. There were no significant differences in the number (%) of subjects with persistently elevated ALT, AST, or bilirubin values across the treatment groups. The incidence of stroke was similar across treatment groups (Table). DU-176b 30 mg qd N=235 DU-176b 60 mg qd N=234 DU-176b 30 mg bid N=244 DU-176b 60 mg bid N=180 Warfarin qd N=250 Bleeding, n (%) (95% CI) Major+CR non-major 7 (3.0) (1.2–6.0) 11 (4.7) (2.4–8.3) 19 (7.8) (4.8–11.9)a 19 (10.6) (6.5–16.0)b 8 (3.2) (1.4–6.2) Major 0 (0) (0–1.6) 1 (0.4) (0–2.4) 5 (2.0) (0.7–4.7) 6 (3.3) (1.2–7.1)a 1 (0.4) (0–2.2) All 13 (5.5) (3.0–9.3) 19 (8.1) (5.0–12.4) 32 (13.1) (9.1–18.0) 33 (18.3) (13.0–24.8)b 20 (8.0) (5.0–12.1) Stroke, n (%) (95% CI) 1 (0.4) (0–2.3) 1 (0.4) (0–2.4) 2 (0.8) (0.1–2.9) 2 (1.1) (0.1–4.0) 4 (1.6) (0.4–4.0) Conclusions : DU-176b 30 mg qd and 60 mg qd dose regimens had a safety profile similar to warfarin in patients with AF. Patients treated with the DU-176b 30 mg bid or 60 mg bid regimens had more bleeding events than occurred with warfarin. These results suggest that the DU-176b 30 mg qd or 60 mg qd regimens are safe and well tolerated. A Phase III trial is needed to determine whether DU-176b will provide a suitable replacement for warfarin in AF patients. CR, clinically relevant. aP&lt;0.05, bP=0.002 to warfarin.

scholarly journals 473 Propensity-matched comparison of left atrial appendage occlusion and direct oral anticoagulation for thromboembolic prevention in octogenarians

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Michele Magnocavallo ◽  
Domenico Giovanni Della Rocca ◽  
Carlo Lavalle ◽  
Cristina Chimenti ◽  
Gianni Carola ◽  
...  
Keyword(s):  
Risk Reduction ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Treatment Strategies ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Left Atrial Appendage Occlusion ◽  
Watchman Device ◽  
Major Bleeding Events

Abstract Aims A significant amount of atrial fibrillation patients does not receive appropriate anticoagulation, owing to contraindications and side effects. Octogenarians have higher competing comorbidities with a remarkable bleeding/thromboembolic (TE) risk. We aimed at analysing the clinical outcomes of LAAO compared with direct oral anticoagulation (DOAC) in octogenarians. Methods and results Data were extracted from two prospective databases including 488 LAAO and 825 DOAC patients. Patients aged 80 years or older accounted for 37.1% (n = 181) and 39.5% (n = 326). In order to attenuate the imbalance in covariates between the groups, a propensity score matching technique was used (covariates: age, sex, CHA2DS2-VASc, and HAS-BLED scores, follow-up duration; tolerance 0.02). This method resulted in matched populations with 108 octogenarian patients per group. The annual stroke/transient ischaemic attack (TIA) risk was estimated based on the CHA2DS2-VASc, and compared to the annualized observed risk, owing to calculate the % risk reduction associated with the two treatment strategies. A total of 216 octogenarians were included in the analysis (84 ± 3 years; CHA2DS2-VASc: 4.9 ± 1.4, HAS-BLED: 3.1 ± 0.9). A Watchman device was successfully deployed in all LAAO ≥ 80 patients; periprocedural adverse events were observed in 2.8% (n = 3) of LAAO patients. During a follow-up of 13 ± 4 months, 3 (2.8%) TE complications (1 stroke, 2 TIA) occurred in LAAO ≥ 80 pts and 4 (3.7%; 1 stroke, 3 TIA) in DOAC ≥ 80 pts (P = 0.99). The annualized risk of stroke/TIA was 2.5% in the first and 3.5% in the second group. Based on the estimated annual TE risk according to the CHA2DS2-VASc score, the % risk reduction after LAAO and DOAC was 54.5% and 36.4%, respectively. Major bleeding events were 3 [1 intracranial, 2 gastrointestinal (GI)] LAAO ≥ 80 pts, and 3 (2 intracranial, 1GI) in DOAC ≥ 80 pts (2.8% in both groups). Minor bleeding events were significantly higher in DOAC ≥ 80 pts [13.0% (n = 14) vs. 2.7% (n = 3); RR: 4.7, 95% CI: 1.4–15.7; P = 0.009]. Conclusions LAAO was safe and similar to DOAC at preventing ischaemic/major bleeding events in a matched population of patients aged ≥80 years. A significantly higher incidence of minor bleeding events was observed in the DOAC group.

Abstract 262: Aspirin vs. Warfarin Therapy Outcomes for Non-Valvular Atrial Fibrillation Patients with Moderate Stroke Risk

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
JaeJin An ◽  
Kristin P Jazdzewski ◽  
Paul T Le ◽  
Nazia Rashid ◽  
Daniel T Lang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Antithrombotic Therapy ◽  
Heart Association ◽  
Therapy Outcomes ◽  
Bleeding Events ◽  
Kaiser Permanente ◽  
Major Bleeding Events ◽  
Risk And Benefit

Background: The American College of Cardiology Foundation and American Heart Association guidelinerecommends aspirin 81-325 mg or warfarin use for Non-Valvular Atrial Fibrillation (NVAF) patients with one risk factor for stroke. This study evaluated outcomes associated with antithrombotic treatment among NVAF patients with CHADS 2 =1 in an integrated healthcare system. Methods: Patients age ≥18 years newly diagnosed with NVAF with a CHADS 2 score=1 at diagnosis were identified between 01/01/2006-12/31/2011 within Kaiser Permanente Southern California’s membership and followed until 12/31/2012. The rate of stroke or systemic embolism (SE) and major bleeding events per 100 person-years were evaluated for: 1) aspirin (ASA) only, 2) warfarin time in therapeutic range (TTR) ≥55%, 3) warfarin TTR <55%, and 4) no antithrombotic therapy. The 55% threshold was selected as the lower bound of reported means from previous studies. Results: Among 7,899patients with CHADS 2 =1, 336 stroke and 34 SE events were observed during the 22,542 person-years of follow-up. ASA only therapy was associated with 2.3 times higher risk of stroke/SE (Rate Ratio [RR] = 2.34 [95% CI: 1.61-3.39]) compared to warfarin TTR ≥55%. ASA only events were similar to warfarin TTR <55% but were 23% lower than no antithrombotic therapy. Major bleeding events were lower in ASA therapy compared to warfarin TTR ≥55% (RR = 1.50 [1.23-1.83]) or warfarin TTR <55% (RR= 4.09 [1.23-1.83]). The higher bleeding rates in no therapy compared to warfarin TTR ≥55% or ASA only needs to be further investigated. Conclusion: ASA therapy was associated with a higher rate of stroke/SE but with a lower rate of bleed compared to TTR ≥55% warfarin in NVAF patients with CHADS 2 =1. These results suggest that treatment decisions should be carefully made based on the risk and benefit assessment in patients whose CHADS 2 =1.

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