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Journal of Translational Medicine Sep 2022This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the effectiveness and safety of new direct oral anticoagulants (NOACs) and warfarin among nonvalvular atrial fibrillation patients with diabetes.
METHODS
The PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched. Five retrospective cohort studies and four subgroup analyses of RCTs were included in this meta-analysis.
RESULTS
A meta-analysis of the data of 26,7272 patients showed that for patients with nonvalvular atrial fibrillation and diabetes, NOACs can significantly reduce the incidence of stroke/systemic embolism (SSE), ischaemic stroke, and haemorrhagic stroke compared with warfarin, with no significant difference in major bleeding and all-cause mortality. Additionally, NOACs were superior to warfarin in the incidence of intracranial bleeding, gastrointestinal bleeding, myocardial infarction, and vascular death.
CONCLUSIONS
Among nonvalvular atrial fibrillation patients with diabetes, NOACs were associated with a lower risk of SSE versus warfarin, with no significant difference in major bleeding. Therefore, NOACs may be a better clinical choice.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Warfarin
PubMed: 36180856
DOI: 10.1186/s12967-022-03652-9 -
British Journal of Clinical Pharmacology Sep 2016Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in... (Meta-Analysis)
Meta-Analysis Review
AIMS
Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed.
RESULTS
A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I(2) = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI: 0.29, 2.71; P = 0.82; I(2) = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI: -0.39, 0.12; P = 0.29; I(2) = 32%) and -0.60 (95% CI: -1.42, 0.23; P = 0.16; I(2) = 79%), respectively.
CONCLUSIONS
Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients.
Topics: Administration, Intravenous; Administration, Oral; Humans; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Recurrence
PubMed: 26679691
DOI: 10.1111/bcp.12866 -
Blood Sep 2020Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported... (Meta-Analysis)
Meta-Analysis
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.
Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Treatment Outcome; Venous Thromboembolism
PubMed: 32396939
DOI: 10.1182/blood.2020005819 -
BMC Pregnancy and Childbirth Nov 2015While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of... (Review)
Review
BACKGROUND
While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available.
METHODS
A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars.
RESULTS
Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births.
CONCLUSIONS
Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.
Topics: Administration, Oral; Cost-Benefit Analysis; Female; Fever; Humans; Labor Stage, Third; Misoprostol; Oxytocics; Oxytocin; Parturition; Postpartum Hemorrhage; Pregnancy; Shivering
PubMed: 26596797
DOI: 10.1186/s12884-015-0749-z -
Journal of the American College of... Jun 2021Delayed intracranial hemorrhage (ICH) after a negative initial head cat scan (CT) is a recognized complication after blunt trauma but the risk of this condition is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Delayed intracranial hemorrhage (ICH) after a negative initial head cat scan (CT) is a recognized complication after blunt trauma but the risk of this condition is unknown. Due to theoretical increased risk in patients on direct oral anticoagulants (DOACs) and inability to monitor degree of anticoagulation, there is a lack of consensus regarding need for additional observation or routine repeat head CT. We hypothesized that patients on DOACs would have a low risk of delayed ICH after blunt head trauma.
METHODS
In June 2020, an electronic literature search of MEDLINE (Ovid), Embase (Elsevier), and Cochrane Library was performed by a medical librarian (TH) using a combination of keywords and subject headings. Databases were searched from inception through June 2020. Included studies reported outcome data on trauma patients greater than 18 years old who were taking anticoagulants and were observed after initial normal head CT. A meta-analysis was performed using a random effects model. The Newcastle-Ottawa Scale (NOS) was utilized for assessing the quality of nonrandomized studies in meta-analyses.
RESULTS
Our electronic search returned 5719 papers and after removal of duplications, 72 underwent full review, and 12 met final inclusion/exclusion criteria. Four thousand eight hundred ninety one of 5289 (92%) patients suffered a ground level fall. Four studies reported routine repeat CT scans on all patients while the remaining only repeated CT scans for symptoms. Overall, 5289 patients were studied and 1263 (23.9%) were on a DOAC. Sixty-nine patients suffered delayed intracranial hemorrhage, 25 on DOAC and 44 on warfarin. The pooled weighted proportion for delayed ICH on DOAC was 2.43% (95% CI, 1.31 – 3.88%) compared to 2.31% (95% CI, 1.26 – 3.66%) on warfarin. Eighty six percent of patients (59/69) who suffered delayed ICH had no clinical consequences while 0.16% (2/1263) of those on DOAC and 0.48% (8/1788) of those on warfarin died from complications following delayed ICH. The overall crude risk of death from delayed ICH while on DOAC or Warfarin was 0.36% (11/3051).
CONCLUSIONS
The risk of delayed ICH following low energy blunt head trauma for patients on DOACs is low, and the risk of a clinically significant bleed is even lower. The practice of routinely observing or systematically repeating head CT in patients on DOACs after low energy blunt head trauma with initially negative head CT may not be warranted.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Head Injuries, Closed; Humans; Intracranial Hemorrhages; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Venous Thromboembolism
PubMed: 33766725
DOI: 10.1016/j.jamcollsurg.2021.02.016 -
The Cochrane Database of Systematic... Jun 2015Cardiac and thoracic surgery are associated with an increased risk of venous thromboembolism (VTE). The safety and efficacy of primary thromboprophylaxis in patients... (Review)
Review
BACKGROUND
Cardiac and thoracic surgery are associated with an increased risk of venous thromboembolism (VTE). The safety and efficacy of primary thromboprophylaxis in patients undergoing these types of surgery is uncertain.
OBJECTIVES
To assess the effects of primary thromboprophylaxis on the incidence of symptomatic VTE and major bleeding in patients undergoing cardiac or thoracic surgery.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2014) and CENTRAL (2014, Issue 4). The authors searched the reference lists of relevant studies, conference proceedings, and clinical trial registries.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants.
DATA COLLECTION AND ANALYSIS
We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.
MAIN RESULTS
We identified 12 RCTs and one quasi-RCT (6923 participants), six for cardiac surgery (3359 participants) and seven for thoracic surgery (3564 participants). No study evaluated fondaparinux, the new oral direct thrombin, direct factor Xa inhibitors, or caval filters. All studies had major study design flaws and most lacked a placebo or no treatment control group. We typically graded the quality of the overall body of evidence for the various outcomes and comparisons as low, due to imprecise estimates of effect and risk of bias. We could not pool data because of the different comparisons and the lack of data. In cardiac surgery, 71 symptomatic VTEs occurred in 3040 participants from four studies. In a study of 2551 participants, representing 85% of the review population in cardiac surgery, the combination of unfractionated heparin with pneumatic compression stockings was associated with a 61% reduction of symptomatic VTE compared to unfractionated heparin alone (1.5% versus 4.0%; risk ratio (RR) 0.39; 95% confidence interval (CI) 0.23 to 0.64). Major bleeding was only reported in one study, which found a higher incidence with vitamin K antagonists compared to platelet inhibitors (11.3% versus 1.6%, RR 7.06; 95% CI 1.64 to 30.40). In thoracic surgery, 15 symptomatic VTEs occurred in 2890 participants from six studies. In the largest study evaluating unfractionated heparin versus an inactive control the rates of symptomatic VTE were 0.7% versus 0%, respectively, giving a RR of 6.71 (95% CI 0.40 to 112.65). There was insufficient evidence to determine if there was a difference in the risk of major bleeding from two studies evaluating fixed-dose versus weight-adjusted low molecular weight heparin (2.7% versus 8.1%, RR 0.33; 95% CI 0.07 to 1.60) and unfractionated heparin versus low molecular weight heparin (6% and 4%, RR 1.50; 95% CI 0.26 to 8.60).
AUTHORS' CONCLUSIONS
The evidence regarding the efficacy and safety of thromboprophylaxis in cardiac and thoracic surgery is limited. Data for important outcomes such as pulmonary embolism or major bleeding were often lacking. Given the uncertainties around the benefit-to-risk balance, no conclusions can be drawn and a case-by-case risk evaluation of VTE and bleeding remains preferable.
Topics: Anticoagulants; Cardiac Surgical Procedures; Hemorrhage; Heparin; Humans; Primary Prevention; Randomized Controlled Trials as Topic; Stockings, Compression; Thoracic Surgical Procedures; Venous Thromboembolism
PubMed: 26091835
DOI: 10.1002/14651858.CD009658.pub2 -
Biomedicines Feb 2023There are recommendations for anticoagulation resumption after gastrointestinal bleeding (GIB), although data addressing this topic by direct oral anticoagulants... (Review)
Review
BACKGROUND
There are recommendations for anticoagulation resumption after gastrointestinal bleeding (GIB), although data addressing this topic by direct oral anticoagulants (DOACs)-treated patients is lacking. We aim to determine the safety and efficacy of restarting DOACs after GIB.
METHODS
Studies that reported rebleeding, thromboembolic events, and mortality after restarting or withholding DOACs were selected. The systematic research was conducted in five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, and Scopus). The random effect model was implemented to calculate the pooled odds ratio (OR). The ROBINS-I tool was used for risk of bias assessment, and the certainty of the evidence was evaluated with the GRADE approach.
RESULTS
Four retrospective cohort studies (1722 patients) were included in the meta-analysis. We did not find a significant increase in the risk of rebleeding in patients restarting DOACs after index GIB (OR = 1.12; 95% CI: 0.74-1.68). The outcomes of thromboembolic events and mortality data were not suitable for meta-analytic calculations. Single studies did not show statistically significant differences. Data quality assessment showed a serious overall risk of bias and very low quality of evidence (GRADE D).
CONCLUSION
DOAC resumption after a GIB episode may not elevate the risk of rebleeding. However, the need for high-quality randomized clinical trials is crucial.
PubMed: 36831090
DOI: 10.3390/biomedicines11020554 -
BMC Cardiovascular Disorders Jan 2017Warfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Warfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of this medication. Recently, several newer direct oral anticoagulants (DOACs) have been approved for use by the food and drug administrations. Unfortunately, these newer drugs have seldom been compared directly with each other. Therefore, this study aimed to compare the bleeding events associated with rivaroxaban and dabigatran in patients treated for non-valvular AF.
METHODS
EMBASE, Medline (National Library of Medicine) and the Cochrane Central Registry of Controlled Trials were searched for studies comparing rivaroxaban with dabigatran using the terms 'rivaroxaban, dabigatran and atrial fibrillation'. Primary endpoints were: any bleeding outcomes, intracranial bleeding and gastro-intestinal (GI) bleeding. Secondary outcomes included stroke/systemic embolism (SE)/transient ischemic attack (TIA), venous thromboembolism and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. The pooled analyses were carried out with RevMan 5.3 software. All the authors had full access to the data and approved the manuscript as written.
RESULTS
A total number of 4895 patients were included. This analysis showed that rivaroxaban was not associated with a significantly higher bleeding event when compared to dabigatran (OR: 1.28, 95% CI: 0.95-1.72; P = 0.11). GI bleeding was similarly manifested between these two DOACs (OR: 0.98, 95% CI: 0.43-2.25; P = 0.97). Even if intracranial bleeding was higher with the use of rivaroxaban, (OR: 2.18, 95% CI: 0.51-9.25; P = 0.29), the result was not statistically significant. Moreover, stroke/SE/TIA and venous thromboembolism were also not significantly different (OR: 0.81, 95% CI: 0.53-1.23; P = 0.32) and (OR: 2.06, 95% CI: 0.73-5.82; P = 0.17) respectively. However, even if mortality favored dabigatran (OR: 1.42, 95% CI: 0.99-2.06; P = 0.06), this result only approached statistical significance.
CONCLUSION
Head to head comparison showed that rivaroxaban was not associated with significantly higher bleeding events compared to dabigatran. Intracranial bleeding, GI bleeding, stroke/SE/TIA, venous thromboembolism and mortality were also not significantly different between these two DOACs. However, due to the limited number of patients analyzed, and which were mainly obtained from observational studies, this hypothesis might only be confirmed in future randomized trials. Furthermore, the CHADS-VASC and HAS-BLED score which might play an important role in predicting bleeding risks should also not be ignored.
Topics: Antithrombins; Atrial Fibrillation; Dabigatran; Factor Xa Inhibitors; Global Health; Hemorrhage; Humans; Incidence; Rivaroxaban; Secondary Prevention; Stroke
PubMed: 28056795
DOI: 10.1186/s12872-016-0449-2 -
Blood Advances Oct 2020Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient... (Meta-Analysis)
Meta-Analysis
Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction occurring in <0.1% to 7% of patients receiving heparin products depending on the patient population and type of heparin. Management of HIT is highly dependent on a sequence of tests for which clinicians may or may not have the results when care decisions need to be made. We conducted systematic reviews of the effects of management strategies in persons with acute HIT, subacute HIT A or B, and remote HIT. We searched Medline, EMBASE, and the Cochrane Database through July 2019 for previously published systematic reviews and primary studies. Two investigators independently screened and extracted data and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. We found primarily noncomparative studies and case series assessing effects of treatments, which led to low to very low certainty evidence. There may be little to no difference in the effects between nonheparin parenteral anticoagulants and direct oral anticoagulants in acute HIT. The benefits of therapeutic-intensity may be greater than prophylactic-intensity anticoagulation. Using inferior vena cava filters or platelet transfusion may result in greater harm than not using these approaches. Evidence for management in special situations, such as for patients undergoing cardiovascular interventions or renal replacement therapy, was also low to very low certainty. Additional research to evaluate nonheparin anticoagulants is urgently needed, and the development of novel treatments that reduce thrombosis without increasing hemorrhage should be a priority.
Topics: Anticoagulants; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thrombosis
PubMed: 33095876
DOI: 10.1182/bloodadvances.2020002963 -
BMC Cardiovascular Disorders Mar 2022The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The real-world studies on recurrent venous thromboembolism (VTE) and bleeding events of non-vitamin K antagonist oral anticoagulants (NOACs) in VTE patients have reported conflicting findings. Our study aimed to provide the direct comparison evidence of different NOACs for VTE patients in clinical practice settings.
METHODS
Search of the medical literature was conducted using PubMed, Web of Science, EMBASE, Clinical Trials.gov, and the Cochrane Library from inception to March 22, 2021. Among the 19,996 citations retrieved, a total of 63,144 patients from 6 studies were analyzed. Clinical outcomes included recurrent VTE, death, and different bleeding events.
RESULTS
Adjusted hazard ratio (HR) analysis suggested that apixaban had significant lower bleeding riskthan rivaroxaban (major, minor and any bleeding: HR = 0.61, 0.56, 0.70; p = 0.008, < 0.0001, 0.006, respectively), but no statistics difference found in recurrent VTE events (HR = 1.02, 95% confidence interval (CI) 0.71-1.47, p = 0.93). There was no significant difference of major bleeding between dabigatran and rivaroxaban (odds ratios (OR) = 0.41, 95% CI 0.09-1.90, p = 0.25), apixaban and dabigatran (OR 0.64, 95% CI 0.15-2.72, p = 0.83). No significant difference was found in the comparison of edoxaban and other NOACs in VTE recurrence, major bleeding and composite outcome.
CONCLUSIONS
In the prevention of bleeding events, apixaban was associated with a lower risk than rivaroxaban, but equivalent efficacy for different NOACs in prevention of recurrent VTE. Evidence generated from the meta-analysis based on real-world data can help to guide selection between apixaban and rivaroxaban in routine clinical practice.
TRIAL REGISTRATION
This systematic review and meta-analysis were conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology statements and was registered with PROSPERO (CRD42019140553).
Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Rivaroxaban; Venous Thromboembolism
PubMed: 35287588
DOI: 10.1186/s12872-022-02550-8