scholarly journals Tinzaparin in Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Increased Risk ◽  
Therapeutic Doses

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Conclusion: Tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

scholarly journals Tinzaparin Safety in Patients With Cancer and Renal Impairment: A Systematic Review

2021 ◽  
Vol 27 ◽  
pp. 107602962097959
Author(s):  
I. A. Vathiotis ◽  
N. K. Syrigos ◽  
E. P. Dimakakos
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Special Populations ◽  
Low Molecular Weight ◽  
Patients With Cancer

Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin, prescribed either as a prophylactic or as a therapeutic regimen for venous thromboembolism in special populations, including cancer patients and patients with renal impairment. We identified prospective studies up to August 2020 reporting safety outcomes for cancer patients and patients with renal impairment on tinzaparin regimens. In patients with cancer major bleeding rates fluctuated between 0.8% and 7%. Patients on tinzaparin exhibited significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin did not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients with renal impairment on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 3.4% of cases; major bleeding rates were higher for cancer patients with renal impairment on therapeutic tinzaparin regimens (4.3 to 10%). Tinzaparin can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a safe choice for special populations at increased risk for thrombosis and bleeding.

Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

2018 ◽  
Vol 118 (01) ◽  
pp. 174-181 ◽  
Author(s):  
Noémie Kraaijpoel ◽  
Nick van Es ◽  
Suzanne Bleker ◽  
Marjolein Brekelmans ◽  
Elise Eerenberg ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Major Bleeding ◽  
Clinical Presentation ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Phase Iii ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractCancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47–1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35–1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.

scholarly journals Tinzaparin in Pregnancy, Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Molecular Weight ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Pregnant Women ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Dose Adjustment ◽  
Low Molecular Weight ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Background: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. Tinzaparin (Innohep®) is the low-molecular-weight heparin with the highest average molecular weight. The purpose of this study is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE, in pregnant women, cancer patients and individuals suffering from renal impairment. Methods: We identified clinical trials reporting safety outcomes for pregnant women, cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. We extracted predefined, clinically relevant outcomes of patients on tinzaparin.Results: For pregnant women on tinzaparin bleeding rates ranged from 9.7% to 10.3%; reported rates of major bleeding events, allergic reactions and thrombocytopenia were low. No maternal deaths or neonatal hemorrhages were recorded. Prophylactic administration of tinzaparin also showed promising results in pregnant women with recurrent unexpected pregnancy loss. In patients with cancer bleeding rates fluctuated between 0.8% and 27%; there was a trend showing that patients on tinzaparin exhibited fewer bleeding events than those on vitamin K antagonists. Bioaccumulation of tinzaparin was not correlated with age, body weight or creatinine clearance. Therapeutic administration of tinzaparin did not produce significant increase in the rates of clinically relevant or major bleeding events in patients with renal impairment. Periodic administration of tinzaparin did not result in bioaccumulation and tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance < 20 ml/min.Conclusions: Tinzaparin represents a thoroughly studied and safe choice for special populations that are at increased risk for both thrombosis and bleeding. Tinzaparin is safe for pregnant women. Current literature supports the use of tinzaparin without dose adjustment in patients with renal impairment and creatinine clearance < 20ml/min.

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with antiphospholipid syndrome: systematic review and meta-analysis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001678
Author(s):  
Nazariy Koval ◽  
Mariana Alves ◽  
Rui Plácido ◽  
Ana G Almeida ◽  
João Eurico Fonseca ◽  
...  
Keyword(s):  
Systematic Review ◽  
Antiphospholipid Syndrome ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Prevention Of Thromboembolic Events

BackgroundDespite vitamin K antagonists (VKA) being the gold standard in the prevention of thromboembolic events in antiphospholipid syndrome (APS), non-vitamin K antagonists oral anticoagulants/direct oral anticoagulants (DOACs) have been used off-label.ObjectiveWe aimed to perform a systematic review comparing DOACs to VKA regarding prevention of thromboembolic events, occurrence of bleeding events and mortality in patients with APS.MethodsAn electronic database search was performed through MEDLINE, CENTRAL and Web of Science. After data extraction, we pooled the results using risk ratio (RR) and 95% CI. Heterogeneity was assessed using the I². The outcomes considered were all thromboembolic events as primary, and major bleeding, all bleeding events and mortality as secondary. Evidence confidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology.ResultsWe included 7 studies and a total of 835 patients for analyses. Thromboembolic events were significantly increased in DOACs arm, compared with VKA—RR 1.69, 95% CI 1.09 to 2.62, I²—24%, n=719, 6 studies. In studies using exclusively rivaroxaban, which was the most representative drug in all included studies, the thromboembolic risk was increased threefold (RR 3.36, 95% CI 1.53 to 7.37). The risks of major bleeding, all bleeding events and mortality were not significantly different from control arm. The grade of certainty of our results is very low.ConclusionsCurrent evidence suggests DOACs use, particularly rivaroxaban, among patients with APS, is less effective than VKA since it is associated with 69% increased risk of thromboembolic events.Trial registration numberCRD42020216178.

scholarly journals Bleeding Risk in a Cohort of Ambulatory Cancer Patients Receiving Outpatient Prophylactic Anticoagulation for Venous Thrombosis Prevention

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 709-709
Author(s):  
Andrew B Wilks ◽  
Daniel Douce ◽  
Steven Ades ◽  
Mary Cushman ◽  
Neil A. Zakai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Bleeding Risk ◽  
Bleeding Events ◽  
Major Bleed ◽  
Prophylactic Dose ◽  
Increased Risk ◽  
Prophylactic Anticoagulation

Background: Recent clinical trials have evaluated the safety and efficacy of direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) prophylaxis in cancer outpatients at high risk for thrombosis. Bleeding risk in these trials were approximately 2% over the first 6 months of therapy. For individual patients, the utility of prophylactic anticoagulation (AC) depends on an acceptable safety profile between bleeding and thrombosis. We investigated whether ambulatory cancer patients on contemporary cancer-directed therapies and prophylactic AC had an increased risk of major bleeds over the first 6 months of therapy. Methods: As part of a single-center prospective cohort study, we assessed consecutive ambulatory patients initiating cancer-directed treatment, risk-stratified these patients for VTE using the Khorana score and educated them about VTE. High risk patients (Khorana score ≥3) were offered prophylactic AC. Major bleeding events and minor bleeding events (based on ISTH standard definitions) were prospectively captured via billing code screening and confirmed by physician review of the medical record. Logistic regression was used to compare the odds of developing a major bleed within 6 months in those who received prophylactic AC compared to those that did not. Results: A total of 1,210 patients were enrolled from October 2015 - June 2018, of which, 640 were women (52.9%). The most common cancers were gastrointestinal 270 (22%), lung 213 (18%), and breast 198 (16%). There were 393 patients (32%) with a Khorana score of 0, 706 (58%) with a Khorana score of 1-2, and 111 (9%) with a score of ≥3. A total of 421 patients received any AC (LMWH or DOAC). Of these, 282 received a prophylactic dose anticoagulant and 139 were receiving a full dose anticoagulant prior to enrolling for other medical reasons. Prophylactic dose anticoagulants prescribed included apixaban in 107 (41%), rivaroxaban in 6 (2.3%), enoxaparin in 119 (45.7%), and other heparin products in 50 (19.2%). A total of 27 (2.33%) major bleeds and 22 (1.81%) minor bleeds occurred within the first 6 months of starting therapy. Of these bleeding events, 8 (2.8%) occurred in those on prophylactic AC, and 6 (4.3%) occurred in those on full dose AC. The odds ratio (OR) of developing a major bleed on any type of AC was 1.78 [CI 0.817-3.88]. The OR of major bleeding on prophylactic AC was 1.49 [CI 0.64-3.479]. The OR of major bleed was highest in lung cancer patients on prophylactic AC (OR 2.81, CI 1.27-6.25). Men, when compared to women, were more likely to bleed on prophylactic AC in the first six month (OR 0.2; CI 0.07-0.52). The OR for major bleed with each 1 year increase in age was 1.02 (CI 0.99, 1.06). The OR of bleeding with a high risk Khorana score (≥3) compared to a lower score was 1.04 (CI 0.73-1.50). Conclusion: During the first six months of therapy, prophylactic AC was associated with an increased risk of major bleeding events in patients on cancer-directed therapy. In this study, the rate of major bleeding was similar as compared to published clinical trials. Neither age nor higher Khorana score were associated with an increased risk of major bleeds in patients on prophylactic AC. The finding that men, when compared to women, and patients with lung cancer may have an increased risk of major bleeding while on prophylactic AC and cancer-directed chemotherapy suggests these groups may warrant both increased education and monitoring to ensure safety while on prophylactic AC. Disclosures No relevant conflicts of interest to declare.

scholarly journals Low- Molecular Weight Heparins (LMWH) Versus Vitamin K Antagonists (VKAs) in the Treatment and Secondary Prevention of Cancer-Associated Venous Thromboembolism (VTE): A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1180-1180 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Lukman Tijani ◽  
Thein H. Oo
Keyword(s):  
Systematic Review ◽  
Secondary Prevention ◽  
Cancer Patients ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Recurrent Vte ◽  
Prevention Of Cancer

Abstract Introduction: Cancer-associated thrombosis accounts for about 20% of all cases of VTE. VTE increases not only mortality but also morbidity in cancer patients. LMWH is currently recommended over VKAs by major consensus guidelines and it is primarily based on a single, large RCT (CLOT trial) and some smaller studies. However, recently published CATCH trial, which enrolled 900 cancer patients with acute VTE, did not detect a statistically significant reduction in recurrent VTE between tinzaparin and warfarin groups. Hereby, we conducted a systematic review and meta-analysis of RCTs to determine the efficacy and safety of LMWH versus VKA in the treatment and secondary prevention of cancer-associated VTE. Methods: MEDLINE and EMBASE databases were searched through June 30, 2016. All potential studies and their references were evaluated for any additional relevant studies. The RCTs which compare LMWH vs VKA in the treatment of VTE were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied. Results: A total of 2196 cancer patients with acute VTE from 6 RCTs and a subgroup of another 2 RCTs were eligible for analysis. Enoxaparin, dalteparin, tinzaparin and nadroparin were used on LMWH group and warfarin or acenocoumarol were used on VKA group. The treatment duration was from 3 to 6 months. The VTE incidence was 77 (6.832%) in LMWH group vs 128 (11.973%) in VKA group with a RR of 0.572 (95% CI: 0.436 to 0.750, P < 0.001). The absolute RD in VTE was -0.051 (95% CI: -0.076 to -0.027, P < 0.001). Major bleeding (MB) events were reported in 49 (4.757%) patients in LMWH group vs 45 (4.473%) in VKA group according to the analysis of 6 RCTs. The pooled relative risk for MB was statistically non-significant at 1.049 (95% CI: 0.705 to 1.562, P = 0.812). Composite clinically relevant non-major (CRNM) and minor bleeding events were noted in 143 (13.883%) patients in LMWH group and in 163 (16.203%) in VKA group according to the analysis of 6 RCTs. The RR for composite CRNM and minor bleeding was statistically significant at 0.773 (95% CI: 0.630 to 0.948, P 0.014), favoring LMWHs over VKAs. Conclusions: Our meta-analysis confirms that LMWHs significantly decrease recurrent VTE events compared to VKAs without increasing MB in patients with cancer-associated VTE. LMWH therapy appears to have less CRNM and minor bleeding events compared to VKAs. Figure Figure. Disclosures Oo: Daiichi Sankyo: Research Funding.

scholarly journals Enoxaparin 20 mg for thromboprophylaxis in severe renal impairment

2018 ◽  
Vol 47 (1) ◽  
pp. 225-234 ◽  
Author(s):  
Lamis R. Karaoui ◽  
Samah Tawil ◽  
Pascale Salameh ◽  
Nibal Chamoun
Keyword(s):  
Renal Failure ◽  
Creatinine Clearance ◽  
Clearance Rate ◽  
Severe Renal Impairment ◽  
Multivariable Analysis ◽  
Venous Thromboembolic Event ◽  
Bleeding Events ◽  
Creatinine Clearance Rate ◽  
Risk Of Bleeding ◽  
Increased Risk

Objective This study was performed to evaluate the efficacy of daily subcutaneous enoxaparin 20 mg in patients with renal failure. Methods This retrospective cohort study included nonsurgical patients aged ≥18 years with a creatinine clearance rate of <30 mL/minute who were prescribed enoxaparin 20 mg subcutaneously (SC) daily for ≥3 days. The main outcome measures were the occurrence of a venous thromboembolic event (VTE) and bleeding events. Results One hundred sixty patients were identified. VTE occurred in 9 patients (5.6%), and bleeding events occurred in 37 (23.1%). Multivariable analysis showed that an age of >75 years was significantly associated with an increased risk of bleeding, while a creatinine clearance rate of 15 to 29 mL/minute was significantly associated with a lower risk of bleeding. Conclusion In patients with renal failure, enoxaparin 20 mg SC daily resulted in a 5.6% incidence of VTE, which is similar to the previously published acceptable incidence of VTE in patients with normal renal function receiving enoxaparin 40 mg SC daily. The incidence of major bleeding events was 10%, which is lower than that previously published in the literature.

scholarly journals A Systematic Review and a Meta-Analysis Comparing Prophylactic and Therapeutic Low Molecular Weight Heparins for Mortality Reduction in 32,688 COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Riccardo Giossi ◽  
Danilo Menichelli ◽  
Arianna Pani ◽  
Elena Tratta ◽  
Alessandra Romandini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Molecular Weight ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Low Molecular Weight ◽  
Full Dose ◽  
Prophylactic Dose ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Therapeutic Doses

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality.Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS).Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14–3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, −3.87, 5.83 days).Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding.Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

2019 ◽  
Vol 45 (08) ◽  
pp. 851-858 ◽  
Author(s):  
David Spirk ◽  
Tim Sebastian ◽  
Martin Banyai ◽  
Jürg H. Beer ◽  
Lucia Mazzolai ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Similar Rate ◽  
Increased Risk

AbstractRenal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41–3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57–2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41–2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14–0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17–2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

Prediction of major and clinically relevant bleeding in patients with VTE treated with edoxaban or vitamin K antagonists

2017 ◽  
Vol 117 (04) ◽  
pp. 784-793 ◽  
Author(s):  
Gary Raskob ◽  
Harry Büller ◽  
Michael Grosso ◽  
George Zhang ◽  
Shannon Winters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Bleeding ◽  
Risk Model ◽  
Vitamin K Antagonists ◽  
Significant Risk ◽  
Study Drug ◽  
Duration Of Treatment ◽  
Bleeding Events ◽  
C Statistic ◽  
Increased Risk

SummaryBetter understanding of risk factors for major bleeding events during anticoagulant treatment for venous thromboembolism (VTE) may help physicians when deciding on intensity and duration of treatment. The primary aim of this study was to identify risk factors for major and clinically relevant bleeding in patients receiving the oral factor Xa inhibitor edoxaban or warfarin for the treatment of acute VTE. We analysed data from 8240 patients who received ≥1 dose of study drug in the Hokusai-VTE study. Bleeding risk factors were evaluated in 4118 patients who received edoxaban and significant variables were combined in a prediction model. We used the C-statistic to estimate model discrimination and bootstrap techniques for internal validation. Major bleeding occurred in 56/4118 (1.4 %) patients given edoxaban and in 66/4122 (1.6 %) patients given warfarin. Clinically relevant bleeding occurred in 349 (8.5 %) and 423 (10.3 %), respectively. Significant risk factors for major bleeding during edoxaban treatment were female sex, concomitant antiplatelet therapy, haemoglobin ≤10 g/dl, history of arterial hypertension, and systolic blood pressure >160 mmHg. The discrimination of the model was high (C-statistic: 0.71) for major bleeding, lower for clinically relevant bleeding (C-statistic: 0.62) and when the model was applied to patients receiving warfarin (C-statistic 0.60). In conclusion, we identified five main predictors of major bleeding in patients receiving edoxaban for the treatment of acute VTE. A risk model based on these factors predicted an increased risk of bleeding with good discrimination.Supplementary Material to this article is available online at www.thrombosis-online.com.

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