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World Journal of Surgical Oncology Feb 2024Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients.
MATERIALS AND METHODS
A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386).
RESULTS
We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46-1.02], I = 0%), major bleeding (RR:1.55 [95% CI:0.82-2.93], I = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4-1.98], I = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC.
CONCLUSION
DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events.
Topics: Humans; Heparin, Low-Molecular-Weight; Anticoagulants; Venous Thromboembolism; Hemorrhage; Neoplasms
PubMed: 38403630
DOI: 10.1186/s12957-024-03341-5 -
International Journal of Molecular... Apr 2023Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between... (Review)
Review
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.
Topics: Humans; Female; Vascular Endothelial Growth Factor A; Uterine Neoplasms; Leiomyoma; Infertility; Uterine Hemorrhage
PubMed: 37108180
DOI: 10.3390/ijms24087011 -
Journal of Psychiatric Research Dec 2022A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
A systematic review was conducted to investigate prevalence, management and outcomes of atrial fibrillation (AF) in people with Serious Mental Illnesses (SMI) versus the general population.
DATA SOURCES
MEDLINE, EMBASE, and PsycINFO were searched for primary research written in English and published between 2004 and 2022.
STUDY SELECTION
A total of 1459 studies were identified in the initial search of which 16 met the inclusion criteria. Studies (n = 4) reporting on ischaemic stroke and major bleeding events were included in the meta-analysis.
DATA EXTRACTION
Two independent reviewers extracted data and assessed risk of bias using the Newcastle-Ottawa Scale. Discrepancies were resolved by consulting a third reviewer.
RESULTS
Low rates of AF were reported among people with SMI suggesting under-recognition or recording gaps. People with SMI and AF were less likely to receive oral anticoagulation therapy compared to the general population. When receiving warfarin, those with bipolar disorder experienced poor anticoagulation control as measured by time in INR therapeutic range. Pooled analysis of risk estimates showed that in patients with identified AF, SMI was not significantly associated with an increased risk of stroke (HR: 1.09; 95%CI: 0.85 to 1.40; I = 60%, p = 0.04) or major bleeding (HR: 1.11; 95%CI: 0.95 to 1.28; I = 57%, p = 0.03) when adjusted for underlying stroke and bleeding risks using the CHA2DS2VASc and HASBLED scales respectively.
CONCLUSION
More research is needed to examine the prevalence, management and outcomes of AF in this population, and to evaluate the effect of the introduction of the novel anti-coagulants on these metrics over time.
Topics: Humans; Atrial Fibrillation; Brain Ischemia; Stroke; Hemorrhage; Anticoagulants; Mental Disorders
PubMed: 36417811
DOI: 10.1016/j.jpsychires.2022.11.002 -
Neurology. Clinical Practice Feb 2018We summarize the existing evidence on the potential benefit of oral anticoagulation (OAC) in intracerebral hemorrhage (ICH) survivors with nonvalvular atrial... (Review)
Review
BACKGROUND
We summarize the existing evidence on the potential benefit of oral anticoagulation (OAC) in intracerebral hemorrhage (ICH) survivors with nonvalvular atrial fibrillation (NVAF).
METHODS
Systematic review of the literature to address the following issues: (1) prevalence of NVAF in ICH survivors, (2) current prescription of OAC, (3) factors associated with resumption of OAC, (4) risk of ischemic stroke (IS) and recurrent ICH, and (5) ideal timing for restarting OAC in ICH survivors with NVAF.
RESULTS
After screening 547 articles, 26 were included in the review. Only 3 focused specifically on patients with ICH as primary event, NVAF as indication for OAC, and recurrent ICH and IS as primary endpoints. In addition, 19 letters to the editor/reviews/editorials/experts' surveys/experts' opinion were used for discussion purposes.
CONCLUSIONS
NVAF is highly prevalent among ICH survivors. The risks of IS, recurrent ICH, and mortality are heightened in this group. Most published data show a net benefit in terms of IS prevention and mortality when anticoagulation is restarted. However, those studies are observational and mostly retrospective, therefore selection bias may play a major role in the results observed in these cohorts. Only randomized controlled trials, either pragmatic or explanatory, can provide more conclusive answers for this important clinical question.
PubMed: 29517050
DOI: 10.1212/CPJ.0000000000000425 -
Journal of the American Heart... Apr 2024Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population.
METHODS AND RESULTS
An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation.
CONCLUSIONS
For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.
Topics: Humans; Atrial Fibrillation; Rivaroxaban; Dabigatran; Stroke; Network Meta-Analysis; Anticoagulants; Hemorrhage; Fibrinolytic Agents; Administration, Oral; Kidney Failure, Chronic; Thromboembolism; Randomized Controlled Trials as Topic
PubMed: 38606775
DOI: 10.1161/JAHA.123.034176 -
The Cochrane Database of Systematic... Apr 2023Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional treatment of PE used unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and vitamin K antagonists (VKAs). Recently, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors. DOACs have characteristics that may be favourable to conventional treatment, including oral administration, a predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. This review reports the efficacy and safety of these drugs in the long-term treatment of PE (minimum duration of three months). This is an update of a Cochrane Review first published in 2015. OBJECTIVES: To assess the efficacy and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of PE.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 2 March 2022. We checked the reference lists of relevant articles for additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which people with a PE confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with a conventional anticoagulant or compared with each other for the long-term treatment of PE (minimum duration three months).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were recurrent PE, recurrent venous thromboembolism (VTE), and deep vein thrombosis (DVT). Secondary outcomes were all-cause mortality, major bleeding, and health-related quality of life. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified five additional RCTs with 1484 participants for this update. Together with the previously included trials, we have included ten RCTs with a total of 13,073 participants. Two studies investigated an oral DTI (dabigatran) and eight studies investigated oral factor Xa inhibitors (three rivaroxaban, three apixaban, and two edoxaban). The studies were of good methodological quality overall. Meta-analysis showed no clear difference in the efficacy and safety of oral DTI compared with conventional anticoagulation in preventing recurrent PE (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.50 to 2.04; 2 studies, 1602 participants; moderate-certainty evidence), recurrent VTE (OR 0.93, 95% CI 0.52 to 1.66; 2 studies, 1602 participants; moderate-certainty evidence), DVT (OR 0.79, 95% CI 0.29 to 2.13; 2 studies, 1602 participants; moderate-certainty evidence), and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; 2 studies, 1527 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision due to the low number of events. There was also no clear difference between the oral factor Xa inhibitors and conventional anticoagulation in the prevention of recurrent PE (OR 0.92, 95% CI 0.66 to 1.29; 3 studies, 8186 participants; moderate-certainty evidence), recurrent VTE (OR 0.83, 95% CI 0.66 to 1.03; 8 studies, 11,416 participants; moderate-certainty evidence), DVT (OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 8151 participants; moderate-certainty evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; 1 study, 4817 participants; moderate-certainty evidence) and major bleeding (OR 0.71, 95% CI 0.36 to 1.41; 8 studies, 11,447 participants; low-certainty evidence); the heterogeneity for major bleeding was significant (I = 79%). We downgraded the certainty of the evidence to moderate and low because of imprecision due to the low number of events and inconsistency due to clinical heterogeneity. None of the included studies measured health-related quality of life.
AUTHORS' CONCLUSIONS
Available evidence shows there is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent PE, recurrent VTE, DVT, all-cause mortality, and major bleeding. The certainty of evidence was moderate or low. Future large clinical trials are required to identify if individual drugs differ in effectiveness and bleeding risk, and to explore effect differences in subgroups, including people with cancer and obesity.
Topics: Humans; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Hemorrhage; Neoplasm Recurrence, Local; Pulmonary Embolism; Venous Thromboembolism
PubMed: 37057837
DOI: 10.1002/14651858.CD010957.pub3 -
Blood Oct 2014Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed... (Meta-Analysis)
Meta-Analysis Review
Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding.
Topics: Administration, Oral; Adult; Anticoagulants; Female; Hemorrhage; Humans; Male; Middle Aged; Vitamin K
PubMed: 25150296
DOI: 10.1182/blood-2014-07-590323 -
GeroScience Feb 2024Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered... (Meta-Analysis)
Meta-Analysis
Safety outcomes of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials.
Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.
Topics: Humans; Aged; Atrial Fibrillation; Warfarin; Rivaroxaban; Dabigatran; Randomized Controlled Trials as Topic; Anticoagulants; Hemorrhage; Aspirin; Pyridines; Thiazoles
PubMed: 37261677
DOI: 10.1007/s11357-023-00825-2 -
Frontiers in Cardiovascular Medicine 2021Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the...
Comparison of the Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DOACs vs. warfarin and update the evidence for treatment of AF and valvular heart disease (VHD). We identified randomized clinical trials (RCTs) and analyses comparing the use of DOACS and Warfarin in AF and VHD, including biological and mechanical heart valves (MHV), updating from 2010 to 2020. Through systematic review and meta-analysis, by using the "Rev Man" program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, while the secondary outcome included intracranial hemorrhage. We performed prespecified subgroup analyses. Data were analyzed by risk ratio (RR) and 95% confidence interval (CI) and the I-square ( ) statistic as a quantitative measure of inconsistency. Risk of bias and methodological quality assessment of included trials was evaluated with the modified Cochrane risk-of-bias tool. We screened 326 articles and included 8 RCTs ( = 14.902). DOACs significantly reduced the risk of stroke/SE (RR 0.80, 95% CI: 0.68-0.94; = 0.008; moderate quality evidence; = 2%) and intracranial hemorrhage (RR 0.40, 95% CI: 0.24-0.66; = 0.0004; = 49%) with a similar risk of major bleeding (RR 0.83, 95% CI: 0.56-1.24; = 0.36; = 88%) compared to Warfarin. In this update, DOACs remained with similar efficacy and safety compared to warfarin in thromboprophylaxis for AF and VHD.
PubMed: 34631818
DOI: 10.3389/fcvm.2021.712585 -
British Journal of Clinical Pharmacology Aug 2017The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND AIMS
The efficacy of proton pump inhibitors (PPIs) has been demonstrated for bleeding peptic ulcers but the route of administration remains controversial. Several studies have demonstrated that high-dose oral PPIs are as effective as intravenous PPIs in reducing recurrent bleeding. However, current guidelines recommend intravenous PPIs after endoscopic treatment. Previous data based on numbers that were too small to enable a firm conclusion to be reached suggested that oral and intravenous PPIs had equivalent efficacy. We undertook a meta-analysis to compare oral and intravenous PPIs in patients with bleeding peptic ulcers after endoscopic management.
METHODS
A literature search was undertaken using MEDLINE, EMBASE and the Cochrane Library, between 1990 and February 2016, to identify all randomized controlled trials (RCTs) that assessed the efficacy of PPIs administered by different routes. Nine RCTs, involving 1036 patients, were analysed. Outcomes were: recurrent bleeding, blood transfusion requirement, duration of hospital stay, a need for repeat endoscopy, surgery and 30-day mortality.
RESULTS
There were no differences in the rebleeding rates [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.60, 1.46; P = 0.77], need for surgery (OR 0.77, 95% CI 0.25, 2.40; P = 0.65), need for repeat endoscopy (OR 0.69, 95% CI 0.39, 1.21; P = 0.19), need for blood transfusion [(MD) -0.03, 95% CI -0.26, 0.19; P = 0.76], duration of hospital stay (MD -0.61, 95% CI -1.45, 0.23; P = 0.16) or 30-day mortality (OR 0.89, 95% CI 0.27, 2.43; P = 0.84) according to the route of administration.
CONCLUSIONS
Oral PPIs represent better value for money, with clinical efficacy equivalent to intravenous PPIs.
Topics: Administration, Intravenous; Administration, Oral; Anti-Ulcer Agents; Endoscopy, Gastrointestinal; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Recurrence; Treatment Outcome
PubMed: 28181291
DOI: 10.1111/bcp.13258