Major Bleeding and Case Fatality Rate with the Direct Oral Anticoagulants in Orthopedic Surgery: A Systematic Review and Meta-Analysis

Abstract Background.Safety and efficacy of direct oral anticoagulants (DOACS) has been established in randomized trials but an increasing number of "real world" data outside clinical trials has become available after approval. In this study we aimed to assess the efficacy and safety of DOACS in population-based studies in the context of non-valvular atrial fibrillation (NVAF), thromboprophylaxis in orthopedic surgery (OS), and treatment of acute venous thromboembolism (VTE). Methods.We conducted a systematic review of observational studies assessing the safety and efficacy of DOACs (including dabigatran, rivaroxaban and apixaban) in patients with NVAF, OS and VTE treatment. Efficacy outcomes included stroke (NVAF studies) and VTE (OS studies). Safety outcomes included major bleeding (MB) (as defined by investigators), gastrointestinal (GI) and central nervous system (CNS) bleeding. If feasible we conducted a meta-analysis of incidence rates (IR) and proportions using both fixed and random effects models. Results.Of 84 potentially relevant studies we included36 full text articles published between 2012 and 2016. Three groups of studies were identified: NVAF (22 studies), thromboprophylaxis in OS (10 studies), and miscellaneous (4 studies).Of the miscellaneous studies, only 1 study assessed DOACS in the treatment of acute VTE. Studies assessing NVAF. The 22 studies included 158,554 patients of which, 70,608 were evaluable for stroke, 80,810 for MB, 88,397 for CNS bleed, and 97,738 for GI bleed. Overall, the percent of patients developing stroke, MB, CNS and GI bleed were similar with both random and fixed models (Table 1). Among NVAF patients, a meta-analysis of studies with follow up information (7 studies, n=40,955) showed that the IR of stroke for all DOACS was 1.8 [95%CI: 1.72-1.98] and 2.3 [95%CI: 1.99-2.61] per 100 person - year (100 PY) for the fixed and random estimates, respectively, regardless of previous vitamin K antagonist (VKA) exposure. The IR of CNS bleeding with dabigatran was 0.6 [95%CI: 0.54-0.72] and 1.3 [95%CI: 0.13-2.47] per 100 PY for fixed and random estimates, respectively. The IR of bleeding-related deaths in NVAF with all DOACS was 0.1 [95%CI: 0.07-0.17] per 100 PY (fixed) and 0.2 [95%CI: 0-0.8] per 100 PY (random). Sensitivity analyses showed that in VKA naïve patients, dabigatran at 110 mg bid (D110) carried a significantly higher risk of stroke than dabigatran 150 mg bid (D150) [RR: 3.4; 95%CI: 2.57-4.50; p<0.0001], whereas in VKA experienced patients the risk of stroke with D110 was similar to D150 [RR: 2.0; 95%CI: 0.76-5.28; p=0.15]. In dabigatran users, VKA naïve patients carried around a 2-fold significant increase in the risk of major bleeding (MB) compared to previous VKA users [RR: 1.8; 95%CI: 1.05-3.12; p=0.03]. While the proportion of CNS bleeding was extremely low with all doses of all DOACS, the risk of GI bleed with D150 was statistically significantly higher than that of D110 in both populations of VKA naïve [RR:1.6; 95%CI: 1.14-2.31; P=0.006], and VKA experienced dabigatran users [RR: 8.3; 95% CI: 3.39-20.46; p<0.0001]. Studies in OS. Studies assessing DOACs in patients undergoing orthopedic surgery (n=27,158) showed a VTE rate of 0.8% [95%CI: 0.73-0.95] (fixed) and 1.5% [95%CI: 1.8-1.11] with (random). The MB rate was 0.7% [95%CI: 0.61-0.81] (fixed) and 2.2% [95%CI: 2.61-1.79] (random). Conclusion.DOACS used in NVAF and orthopedic surgery are effective and safe in real-world studies as in RCTs. However, in NVAF, dabigatran dose and previous exposure to VKA seem to impact the risks of stroke, MB, and GI bleed. CNS bleed rates were consistently low with all DOACS at all doses, whether in VKA naïve or VKA experienced populations. Data for apixaban and VTE treatment is currently limited. Disclosures Lazo-Langner: Pfizer: Honoraria; Daiichi Sankyo: Research Funding; Bayer: Honoraria.

Download Full-text

FATAL BLEEDING, CASE-FATALITY RATE OF MAJOR BLEEDING AND ALL-CAUSE MORTALITY IN PATIENTS TAKING TARGET-SPECIFIC ORAL ANTICOAGULANT, A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(15)62052-6 ◽

2015 ◽

Vol 65 (10) ◽

pp. A2052

Author(s):

Chatree Chai-Adisaksopha ◽

Christopher Hillis ◽

Tetsuya Isayama ◽

Mark Crowther

Keyword(s):

Major Bleeding ◽

Oral Anticoagulant ◽

Case Fatality Rate ◽

Meta Analysis ◽

Case Fatality ◽

Controlled Trials ◽

Fatality Rate ◽

Randomized Controlled ◽

Fatal Bleeding ◽

All Cause Mortality

Download Full-text

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

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa168 ◽

2020 ◽

Cited By ~ 3

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.

Download Full-text

Global epidemiology of septic shock: a protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-032289 ◽

2019 ◽

Vol 9 (11) ◽

pp. e032289

Author(s):

Frank Leonel Tianyi ◽

Joel Noutakdie Tochie ◽

Celestin Danwang ◽

Aime Mbonda ◽

Mazou N Temgoua ◽

...

Keyword(s):

Systematic Review ◽

Septic Shock ◽

Case Fatality Rate ◽

Hospital Admissions ◽

Meta Analysis ◽

Case Fatality ◽

Primary Study ◽

Fatality Rate ◽

Cross Sectional ◽

Global Epidemiology

BackgroundSeptic shock is a life-threatening infection frequently responsible for hospital admissions or may be acquired as nosocomial infection in hospitalized patients with resultant significant morbidity and mortality . There is a dearth of data on a résumé and meta-analysis on the global epidemiology of this potentially deadly condition. Therefore, we propose the first systematic review to synthesize existing data on the global incidence, prevalence and case fatality rate of septic shock worldwide.MethodsWe will include cross-sectional, case-control and cohort studies reporting on the incidence, and case fatality rate of septic shock. Electronic databases including PubMed, Embase, WHO Global Health Library and Web of Science will be searched for relevant records published between 1 January 2000 and 31 August 2019. Independents reviewers will perform study selection and data extraction, as well as assessment of methodological quality of included studies. Appropriate meta-analysis will then be used to pool studies judged to be clinically homogenous. Egger’s test and funnel plots will be used to detect publication bias. Findings will be reported and compared by human development level of countries.Ethics and disseminationBeing a review, ethical approval is not required as it was obtained in the primary study which will make up the review. This review is expected to provide relevant data to help in evaluating the burden of septic shock in the general population. The overall findings of this research will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019129783.

Download Full-text

Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-019-0673-5 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Nina Droz ◽

Yingfen Hsia ◽

Sally Ellis ◽

Angela Dramowski ◽

Mike Sharland ◽

...

Keyword(s):

Systematic Review ◽

Blood Culture ◽

Case Fatality Rate ◽

Bacterial Pathogens ◽

Meta Analysis ◽

Case Fatality ◽

Bloodstream Infections ◽

Fatality Rate ◽

Middle Income ◽

Middle Income Countries

Abstract Background Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile. Methods We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for “sepsis” and “low-middle-income countries” in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used. Results We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% [95% CI: 12.0–27.5%]; 15.5% [8.4–24.4%] in Africa and 28.0% [13.2–45.8%] in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% [52.2–74.9]) and 1858 were Gram-positive (35.8% [24.9–47.5]). In Asia, Salmonella typhi (26.2%) was the most commonly isolated pathogen, followed by Staphylococcus aureus (7.7%) whereas in Africa, S. aureus (17.8%) and Streptococcus pneumoniae (16.8%) were predominant followed by Escherichia coli (10.7%). S. aureus was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas E. coli was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% [6.6–20.2%]. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each. Conclusions We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes.

Download Full-text

Case fatality rate in COVID-19: a systematic review and meta-analysis

10.1101/2020.04.01.20050476 ◽

2020 ◽

Cited By ~ 2

Author(s):

Chanaka Kahathuduwa ◽

Chathurika Dhanasekara ◽

Shao-Hua Chin

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Critical Illness ◽

Publication Bias ◽

Case Fatality Rate ◽

Meta Analysis ◽

Case Fatality ◽

Severe Illness ◽

Fatality Rate ◽

Meta Regression

AbstractBackgroundEstimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression.MethodsPRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors.ResultsThe meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity.ConclusionsRisk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.

Download Full-text

Global epidemiology of acute generalised peritonitis: a protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-034326 ◽

2020 ◽

Vol 10 (1) ◽

pp. e034326

Author(s):

Joel Noutakdie Tochie ◽

Ndip Valirie Agbor ◽

Tianyi Tianyi Frank Leonel ◽

Aime Mbonda ◽

Desmond Aji Abang ◽

...

Keyword(s):

Systematic Review ◽

Case Fatality Rate ◽

Data Extraction ◽

Meta Analysis ◽

Case Fatality ◽

Published Data ◽

Fatality Rate ◽

Global Epidemiology ◽

Ethical Approval ◽

Registration Number

IntroductionGlobally, acute generalised peritonitis (AGP) is a common medical and surgical emergency which is a major contributor to non-trauma deaths despite improvements in diagnosis and surgical and intensive care management. In order to determine the global burden of AGP, geared at tailoring key interventions to curb its morbidity and mortality, we proposed this first ever systematic review and meta-analysis to estimate the contemporary prevalence, and to determine the most frequent AGP and the case fatality rate of AGP, at the global scene.Methods and analysisWe intend to searchAfricanJournalsOnline, Americana em Ciências da Saúde, Citation index, EMBASE, Global Index Medicus, Literatura Latino Africa Index Medicus, Medline and Scientific Electronic Library Online databases from 1 January 2009 to 31 July 2019 to identify studies that reported the prevalence, types of AGP, and case fatality rate of AGP in the global population without any language restrictions. Study selection, data extraction and risk of bias assessment will be conducted independently at each level by a pair of independent investigators. Random-effects meta-analysis will be used to pool studies judged to be clinically homogeneous. The presence of heterogeneity will be evaluated using the χ² test on Cochrane’s Q statistic and quantified with the I² statistics. Publication bias will be evaluated statistically and visually using the Egger’s test and funnel plots, respectively. Findings will be reported and compared by countries, WHO regions and globally.Ethics and disseminationSince this study will be based on published data, it does will not require an ethical approval. The findings will be published in a scientific peer-reviewed journal. They will also be presented at scientific conferences and to relevant public health actors.PROSPERO registration numberCRD42019143331.

Download Full-text

DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines

Blood Advances ◽

10.1182/bloodadvances.2019000840 ◽

2020 ◽

Vol 4 (7) ◽

pp. 1512-1517 ◽

Cited By ~ 7

Author(s):

Ignacio Neumann ◽

Ariel Izcovich ◽

Yuqing Zhang ◽

Gabriel Rada ◽

Susan R. Kahn ◽

...

Keyword(s):

Systematic Review ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Treatment Phase ◽

Term Treatment ◽

Cochrane Central Register ◽

Medical Patients ◽

Short Term Treatment

Abstract Venous thromboembolism (VTE) is a relatively frequent complication in hospitalized patients, especially in those with risk factors. The benefit of using direct oral anticoagulants (DOACs) for prevention is controversial. This systematic review was performed as part of the American Society of Hematology (ASH) guidelines on VTE, developed in partnership with McMaster University. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Epistemonikos were used as data sources from date of inception to November 2019. We included randomized trials in patients hospitalized for an acute medical disease, evaluating any DOACs vs other pharmacological prophylaxis, and included 3 trials with low risk of bias. We analyzed the effects of DOACs vs low-molecular-weight heparins (LMWHs) at 2 different time points: at the end of the short-term treatment phase (both drugs given for the same period of time) and at the end of the extended prophylaxis period (extended DOACs vs a shorter course of LMWHs). We observed that the use of DOACs did not reduce the risk of pulmonary embolism or symptomatic deep venous thrombosis (DVT) in comparison with LMWHs. However, the risk of major bleeding was slightly increased. Additionally, we observed that the benefit of DOACs previously reported was largely based on the reduction of asymptomatic DVT and was not apparent when only symptomatic events were considered. The use of DOACs in hospitalized medical patients slightly increases the risk of major bleeding with no appreciable benefit over LMWHs.

Download Full-text