A Meta-Analysis of Case Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding in Patients with Cancer

2020 ◽  
Vol 120 (04) ◽  
pp. 702-713 ◽  
Author(s):  
Alym Abdulla ◽  
Wendy M. Davis ◽  
Namali Ratnaweera ◽  
Elena Szefer ◽  
Brooke Ballantyne Scott ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Case Fatality Rate ◽  
Meta Analysis ◽  
Case Fatality ◽  
Fatality Rate ◽  
Patients With Cancer ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Abstract Background Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. Methods We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. Results Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1–27.8) and 1.9 (95% CI: 0.8–4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6–30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3–16.7) and 0.8 (95% CI: 0.3–2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5–21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. Conclusion In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.

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.

Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

2013 ◽  
Vol 110 (10) ◽  
pp. 834-843 ◽  
Author(s):  
Ana Alfonso ◽  
David Jiménez ◽  
Carmen Fernández Capitán ◽  
Paolo Prandoni ◽  
Philip S. Wells ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Case Fatality Rate ◽  
Real Life ◽  
Case Fatality ◽  
Fatality Rate ◽  
Duration Of Therapy ◽  
Fatal Bleeding ◽  
Recurrent Vte ◽  
Over Time

SummaryIn patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a ‘real life’ population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2–14.2) for recurrent VTE, and 19.7% (95% CI, 17.4–22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6–18.9), compared to 2.0% (95% CI, 0–4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5–23.1) during the first three months, compared to 18.2% (95% CI, 14.0–23.2) beyond this period. The CFR of recurrent VTE was higher in patients initially presenting with PE (18.5%; 95% CI, 15.3–22.1) than in those with DVT (6.3%; 95% CI, 4.5–8.6), and in patients with provoked VTE (16.3%; 95% CI, 13.6–19.4) than in those with unprovoked VTE (5.5%; 95% CI, 3.5–8.0). In conclusion, the CFR of recurrent VTE decreased over time during anticoagulation, while the CFR of major bleeding remained stable. The CFR of recurrent VTE was higher in patients initially presenting with PE and in those with provoked VTE.

Abstract 12901: Novel Oral Anticoagulants Are Associated With Decreased Recurrence of Venous Thromboembolism in Patients With Cancer: An Updated Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sunil Upadhaya ◽  
Seetharamprasad Madala ◽  
Sunil Badami
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Novel Oral Anticoagulants ◽  
P Value ◽  
Patients With Cancer ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Recurrent Vte

Introduction: Patients with cancer are at high risk for recurrent thromboembolic phenomenon. Use of novel oral anticoagulants (NOAC) for treatment of venous thromboembolism (VTE) in such patients is controversial. We conducted this updated meta-analysis to evaluate the pooled efficacy and safety of NOAC in patients with cancer. Methods: We did systematic search of PubMed and Cochrane library databases for randomized controlled trials comparing NOAC with low molecular weight heparin (LMWH) for VTE treatment in cancer patients till April 2020. The efficacy outcomes were recurrent VTE and all-cause mortality rates, and the primary safety outcome was incidence of major bleeding rate. Results: Four randomized controlled studies comparing NOAC with LMWH (1446 patients in NOAC group and 1448 patients in LMWH group) were included in our study. Use of NOAC lead to significant reduction in recurrent VTE rate (odds ratio (OR): 0.55 [0.36-0.84], I 2 = 45 %, p value = 0.006) (Figure 1). However, we did not find any significant difference in rate of major bleeding (OR: 1.30 [0.76-2.23], I 2 = 35%, p value = 0.34) (Figure 2) and all-cause mortality (OR: 1 [0.80 - 1.26], I 2 = 33%, p value = 0.98). Conclusions: This updated meta-analysis showed comparatively lower pooled recurrent VTE rate in patient being treated with NOAC, whereas similar rates of major bleeding and all-cause death. NOAC are more efficacious and has similar safety profile compared with LMWH.

scholarly journals Clinical Characteristics and Outcomes of COVID-19–Infected Cancer Patients: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Hua Zhang ◽  
Han Han ◽  
Tianhui He ◽  
Kristen E Labbe ◽  
Adrian V Hernandez ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Case Fatality Rate ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Case Fatality ◽  
The United States ◽  
Fatality Rate ◽  
Patients With Cancer ◽  
Increased Risk

Abstract Background Previous studies have indicated coronavirus disease 2019 (COVID-19) patients with cancer have a high fatality rate. Methods We conducted a systematic review of studies that reported fatalities in COVID-19 patients with cancer. A comprehensive meta-analysis that assessed the overall case fatality rate and associated risk factors was performed. Using individual patient data, univariate and multivariable logistic regression analyses were used to estimate odds ratios (OR) for each variable with outcomes. Results We included 15 studies with 3019 patients, of which 1628 were men; 41.0% were from the United Kingdom and Europe, followed by the United States and Canada (35.7%), and Asia (China, 23.3%). The overall case fatality rate of COVID-19 patients with cancer measured 22.4% (95% confidence interval [CI] = 17.3% to 28.0%). Univariate analysis revealed age (OR = 3.57, 95% CI = 1.80 to 7.06), male sex (OR = 2.10, 95% CI = 1.07 to 4.13), and comorbidity (OR = 2.00, 95% CI = 1.04 to 3.85) were associated with increased risk of severe events (defined as the individuals being admitted to the intensive care unit, or requiring invasive ventilation, or death). In multivariable analysis, only age greater than 65 years (OR = 3.16, 95% CI = 1.45 to 6.88) and being male (OR = 2.29, 95% CI = 1.07 to 4.87) were associated with increased risk of severe events. Conclusions Our analysis demonstrated that COVID-19 patients with cancer have a higher fatality rate compared with that of COVID-19 patients without cancer. Age and sex appear to be risk factors associated with a poorer prognosis.

scholarly journals Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
Doaa Attia ◽  
Xuefei Jia ◽  
Mailey L Wilks ◽  
Barbara Tripp ◽  
Christopher D'Andrea ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Cleveland Clinic ◽  
Treatment Groups ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte ◽  
Cancer Associated Thrombosis

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P>0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

Long-term risk of major bleeding after discontinuing anticoagulation for unprovoked venous thromboembolism: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Faizan Khan ◽  
Alvi Rahman ◽  
Tobias Tritschler ◽  
Marc Carrier ◽  
Clive Kearon ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Case Fatality ◽  
Incidence Rates ◽  
Bleeding Events ◽  
Randomized Controlled ◽  
Fatal Bleeding

Background: The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Objectives: To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE who had completed ≥3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies. Results: Of 1123 records identified by the search, 20 studies (17 RCTs) and 8740 patients were included in the analysis. During 13 011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n=41) and fatal bleeding (n=7) per 100 person-years was 0.35 (95% confidence interval [CI], 0.20-0.54) and 0.09 (95% CI, 0.05-0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI, 0.4%-2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI, 10.6%-31.1%). Conclusions: Patients with a first unprovoked VTE have a non-trivial risk of major bleeding once anticoagulants are discontinued. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.

scholarly journals Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis

Blood ◽  
2020 ◽  
Vol 136 (12) ◽  
pp. 1433-1441 ◽  
Author(s):  
Frits I. Mulder ◽  
Floris T. M. Bosch ◽  
Annie M. Young ◽  
Andrea Marshall ◽  
Robert D. McBane ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Patients With Cancer ◽  
Recurrent Vte

Abstract Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.

Bleeding and Thromboembolic Events after Termination of Therapy with Idraparinux for Prevention of Recurrent Venous Thromboembolism-Observation after the van Gogh Trials.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1877-1877
Author(s):  
Job Harenberg ◽  
Ingrid Joerg ◽  
Antje Hagedorn ◽  
Christina Giese
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Half Life ◽  
Postoperative Bleeding ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Factor V Leiden Mutation ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Abstract The long acting polymethylated antithrombotic compound Idraparinux has been investigated in the vanGogh trials for prevention of recurrent venous thromboembolism (VTE) using once weekly subcutaneous injections for 3–6 months (vanGogh PE and DVT trial) and for additional 6 months (vanGogh Extension trial). After termination of the studies Idraparinux was eliminated with a half live of 60 days or longer (Harenberg et al, submitted). We followed-up the patients (n=23) at our center for bleeding events, recurrent VTE and other severe events over 15 months. During the study period 2 major bleeding complications occurred in patients randomized to warfarin (days 70 and 186). During follow-up, 2 patients initially randomized to Idraparinux suffered from major bleeding events (days 65 and 140 during follow-up). Bleeding was related to an additional therapy of warfarin or low-molecular-weight heparin. At that time, the long elimination half life time of Idraparinux was unknown. One patient required continuation of anticoagulation due to homocygous factor V Leiden mutation and received warfarin starting one week after termination of idraparinux. At day 65 he was hospitalized because of a major intramuscular bleeding. One patient underwent total hip replacement at day 140 of follow-up receiving nadroparin for prophylaxis of VTE and developed a major postoperative bleeding with reoperation and transfusion. The concentrations of Idraparinux were 0,16μg/ml in each patient. Thereafter the long elimination time of Idraparinux was taken into consideration. In 1 of the patients warfarin was started at a 0.1μg/ml Idrparinux and titrated slowly into an INR range of 1.6 to 2.0 until Idrapaninux decreased to 0.05μg/ml. In the other patient postoperative prophylaxis of VTE was performed with LMWH at 0,01μg/ml Idraparinux (day 571 of follow-up). No adverse events occurred in both patients. During follow-up VTE occurred in 2 patients each initially randomized to warfarin (days 58 and 406) and Idraparinux (days 266 and 381), respectively. The concentrations of idraparinux were <0.01μg/ml in both patients. The data show that the very long half life of Idraparinux may lead to serious bleeding complications, if anticoagulation is given on top of the circulating compound within 3 or 4 months after termination of therapy. Cautious anticoagulation during this period may avoid bleeding. Recurrent VTE occurs late after termination of Idraparinux but in probably to the same frequence as after termination of warfarin.

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