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Cardiovascular Drugs and Therapy Aug 2022Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis Review
Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation and (Morbid) Obesity or Low Body Weight: a Systematic Review and Meta-Analysis.
PURPOSE
Oral anticoagulants are crucial for preventing systemic thromboembolism in atrial fibrillation (AF), with guidelines preferring non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in the general AF population. However, as NOACs are administered in fixed doses, concerns of unintentional underdosing in morbidly obese patients and unintentional overdosing in underweight patients have emerged. Therefore, a critical appraisal of the benefit-risk profile of NOACs in AF patients across the body weight spectrum is needed.
METHODS AND RESULTS
After searching Medline, this systematic review discusses the impact of body weight on the risk-benefit profile of NOACs versus VKAs. The meta-analysis demonstrated that NOAC use in obese and class III obese AF patients (body mass index (BMI) ≥ 30 and ≥ 40 kg/m, respectively) was associated with significantly lower stroke/systemic embolism (stroke/SE) risks (RR 0.82, 95%CI [0.71-0.96] and RR 0.75, 95%CI [0.64-0.87], respectively), similar to lower major bleeding risks (RR 0.83, 95%CI [0.69-1.00] and RR 0.74, 95%CI [0.57-0.95], respectively) and similar mortality risks (RR 0.92, 95%CI [0.73-1.15] and RR 1.17, 95%CI [0.83-1.64], respectively) compared to VKAs. In AF patients ≤ 60 kg, significantly lower stroke/SE (RR 0.63, 95%CI [0.56-0.71]) and major bleeding risks (RR 0.71, 95%CI [0.62-0.80]), but similar mortality risks (RR 0.68, 95%CI [0.42-1.10]), were observed for NOAC- versus VKA-treated patients.
CONCLUSION
The benefit-risk profile of NOACs seems preserved in (morbidly) obese AF patients and patients with low body weight. However, more data are needed on underweight AF patients (BMI < 18.5 kg/m) and on differences between NOACs in these patients.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Obesity, Morbid; Stroke; Thinness; Warfarin
PubMed: 33428092
DOI: 10.1007/s10557-020-07122-6 -
Ageing Research Reviews Dec 2022Frailty is common in older patients with atrial fibrillation (AF). Current guidelines recommend oral anticoagulant therapy (OAT) except in case of severe frailty or... (Review)
Review
Impact of frailty models on the prescription of oral anticoagulants and on the incidence of stroke, bleeding, and mortality in older patients with atrial fibrillation: a systematic review.
BACKGROUND
Frailty is common in older patients with atrial fibrillation (AF). Current guidelines recommend oral anticoagulant therapy (OAT) except in case of severe frailty or reduced life expectancy, but definitive evidence on which "frailty" tools may help to identify older AF patients expected to derive little or no benefit from OAT is still lacking. Some persistent uncertainties may derive from the different clinical implications that the two major models of frailty, namely the frail phenotype (FP) and the deficit accumulation model (DAM), underlie. We thus conducted a systematic review of published studies to examine the association of the presence of frailty, categorized according to the FP and DAM, with 1) OAT prescription and 2) incidence of clinical outcomes (all-cause mortality, stroke and/or systemic embolism and major or clinically relevant non-major bleeding) in patients receiving OAT.
METHODS
Embase and MEDLINE were searched from inception until May 31st, 2022, for studies using a validated tool to identify frailty in subjects aged 65 years or older with a diagnosis of non-valvular AF; only studies on patients prescribed an OAT were considered eligible for the analyses involving clinical outcomes. The protocols for each review question have been registered in PROSPERO database (CRD42022308623 and CRD42022308628).
FINDINGS
Twenty-three studies exploring the association between frailty and OAT prescription on a total of 504 719 subjects were included. Patients with increasing severity of DAM frailty showed consistently lower OAT prescription rates than non-frail patients, whereas use of OAT did not significantly differ between patients with the FP compared with non-frail subjects. Eleven studies exploring the association between frailty and clinical outcomes on a total of 41 985 individuals receiving oral anticoagulation were included. Compared with non-frail subjects, a higher risk of all-cause mortality and clinical outcomes could be observed for AF patients prescribed with OAT with severe frailty according to the DAM, with inconclusive findings for the FP. High levels of heterogeneity were observed in both groups of studies; therefore, a meta-analysis was not performed.
CONCLUSIONS
Due to the great heterogeneity among different validated frailty measures, indiscriminately relying on "frailty" should not be regarded as the gold standard for clinical decision-making about stroke prevention in older AF patients. Present findings suggest that severe frailty according to the DAM is associated with less use of OAT and increased risk of all-cause mortality, thereby representing at the moment the most reasonable tool to efficiently recognize patients with limited life expectancy and for whom there is so far scant, if any, evidence of a clinical benefit of OAT.
Topics: Humans; Atrial Fibrillation; Incidence; Anticoagulants; Stroke; Hemorrhage; Frailty; Prescriptions; Administration, Oral
PubMed: 36270605
DOI: 10.1016/j.arr.2022.101761 -
Expert Opinion on Drug Safety Oct 2015We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed a systematic review and meta-analysis of the risk of oral and gastrointestinal (GI) mucosal injury associated with ramucirumab.
PATIENTS AND METHODS
Eligible studies included randomized Phase II and III trials of patients with solid tumors on ramucirumab: describing events of stomatitis, diarrhea, GI perforation and GI hemorrhage.
RESULTS
Our search strategy yielded 167 potentially relevant citations from Pubmed/Medline, CENTRAL Cochrane registry, European society of medical oncology meeting abstracts and American Society of Clinical Oncology meeting library. After exclusion of ineligible studies, a total of 11 clinical trials were considered eligible for the meta-analysis. The RR of all-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 1.62 (95% CI 1.31 - 2.00; p < 0.00001), 1.15 (95% CI 1.07 - 1.24; p < 0.0001), 3.29 (95% CI 1.54 - 7.04; p = 0.002) and 1.92 (95% CI 1.03 - 3.57; p = 0.04), respectively. The RR of high-grade stomatitis, diarrhea, GI perforation and GI hemorrhage were 2.72 (95% CI 1.76 - 4.19; p < 0.00001), 1.28 (95% CI 0.96 - 1.71; p = 0.09), 3.37 (95% CI 1.51 - 7.54; p = 0.03) and 1.26 (95% CI 0.79 - 2.01; p = 0.34), respectively.
CONCLUSIONS
Our meta-analysis has demonstrated that ramucirumab-based combination treatment is associated with an increased risk of high-grade stomatitis and GI perforation compared to control treatment.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Gastrointestinal Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic; Ramucirumab
PubMed: 26313327
DOI: 10.1517/14740338.2015.1074677 -
American Journal of Cardiovascular... Nov 2023Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC).
OBJECTIVE
This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC.
METHODS
A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3.
RESULTS
Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08).
CONCLUSION
DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.
Topics: Humans; Atrial Fibrillation; Prospective Studies; Anticoagulants; Thromboembolism; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Ischemic Stroke; Liver Cirrhosis; Vitamin K; Administration, Oral; Stroke
PubMed: 37639201
DOI: 10.1007/s40256-023-00598-1 -
Oral Surgery, Oral Medicine, Oral... Mar 2023The recommendations for the management of direct oral anticoagulants (DOACs) in oral surgery are inconsistent. The present review evaluated whether DOACs increase the... (Review)
Review
OBJECTIVE
The recommendations for the management of direct oral anticoagulants (DOACs) in oral surgery are inconsistent. The present review evaluated whether DOACs increase the risk of bleeding during oral surgery and postoperative complications.
STUDY DESIGN
The patients undergoing oral surgery and receiving a DOAC were compared with the patients receiving a DOAC different from the exposure, a vitamin K antagonist (VKA), or no anticoagulant. Three electronic databases were searched for eligible clinical trials and systematic reviews. The risk of bias was assessed, data were extracted, a meta-analysis was done, and the Grading of Recommendations, Assessment, Development and Evaluations certainty-of-evidence ratings were determined.
RESULTS
Three clinical trials comparing patients receiving DOAC medication with patients on a VKA were eligible. A meta-analysis of bleeding 7 days postoperatively detected no significant differences between patients continuing DOAC or VKA medication during and after surgery. All of the point estimates favored uninterrupted DOAC over VKA therapy. Tranexamic acid was topically administered to some patients.
CONCLUSIONS
Based on an interpreted trend among 3 studies with mixed patient populations, the risk of bleeding during the first 7 postoperative days may be lower for patients on uninterrupted DOAC than VKA therapy (⨁⨁⭘⭘), but the effect size of the risk is unclear. 80 of 274 included patients experienced postoperative bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Oral Surgical Procedures; Postoperative Hemorrhage; Tranexamic Acid; Vitamin K
PubMed: 36100547
DOI: 10.1016/j.oooo.2022.07.003 -
Journal of Cardiovascular... Aug 2019We sought to examine whether continuing oral anticoagulation (OAC) after catheter ablation (CA) for atrial fibrillation (AF) is associated with improved outcomes. OAC... (Meta-Analysis)
Meta-Analysis
Oral anticoagulation after catheter ablation of atrial fibrillation and the associated risk of thromboembolic events and intracranial hemorrhage: A systematic review and meta-analysis.
AIMS
We sought to examine whether continuing oral anticoagulation (OAC) after catheter ablation (CA) for atrial fibrillation (AF) is associated with improved outcomes. OAC reduces morbidity and mortality in patients with AF. However, the continuation of OAC following the blanking period of CA is controversial due to conflicting published data.
METHODS
A systematic review of Medline, Cochrane, and Embase was performed for studies comparing patients who were continued on OAC (ON-OAC) vs those in which OAC was discontinued (OFF-OAC). CHA DS VASc score had to be available for the classification of patients into high- or low-risk cohorts (CHA DS VASc ≥ 2 and ≤ 1, respectively). The primary efficacy outcome was thromboembolic events (TE). Intracranial hemorrhage (ICH) was the primary safety outcome.
RESULTS
Five studies comprising 3956 patients were included (mean age, 61.1 ± 2.9 years; 72.4% male, CHA DS VASc ≤ 1 50.1%; CHA DS VASc ≥ 2 49.9%). After a mean follow-up of 39.6 ± 11.7 months, OAC-continuation was associated with a significant decrease in risk of TE in the high-risk cohort (CHA DS VASc ≥ 2) (risk ratio [RR] 0.41, 95% confidence interval [CI] 0.21-0.82, P = .01) with a RR reduction of 59%. ICH was significantly higher in the ON-OAC group (RR, 5.78; 95% CI, 1.33-25.08; P = .02). No significant benefit was observed in the low-risk cohort ON-OAC after the blanking period.
CONCLUSION
Continuation of OAC after CA of AF with CHA DS VASc ≥ 2 is associated with a significant decreased TE risk and a favorable net clinical benefit in spite of ICH being significantly increased in the ON-OAC group. Continued OAC offers no benefit with CHA DS VASC ≤ 1.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Risk Assessment; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome
PubMed: 31257677
DOI: 10.1111/jce.14052 -
Clinical Gastroenterology and... Nov 2017Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Non-vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs.
METHODS
We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug.
RESULTS
Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80-1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64-1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77-1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67-1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04-1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15-1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64-1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78-1.11). These subgroup findings were not observed in other sensitivity analyses.
CONCLUSIONS
In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.
Topics: Anticoagulants; Dabigatran; Gastrointestinal Hemorrhage; Humans; Risk Assessment; Rivaroxaban; Stroke; Thromboembolism
PubMed: 28458008
DOI: 10.1016/j.cgh.2017.04.031 -
American Journal of Cardiovascular... Sep 2022Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF... (Meta-Analysis)
Meta-Analysis
Comparison of the Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants with Warfarin in Atrial Fibrillation Patients with a History of Bleeding: A Systematic Review and Meta-Analysis.
BACKGROUND
Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding.
METHODS
We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021.
RESULTS
Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p = 0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p < 0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p = 0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p < 0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p < 0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p < 0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p = 0.01).
CONCLUSIONS
NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Retrospective Studies; Stroke; Treatment Outcome; Warfarin
PubMed: 35292921
DOI: 10.1007/s40256-022-00530-z -
European Journal of Clinical... Aug 2023Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We... (Meta-Analysis)
Meta-Analysis Review
Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis.
BACKGROUND
Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF).
METHODS
A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.
RESULTS
Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7).
CONCLUSIONS
Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.
Topics: Humans; Atrial Fibrillation; Dabigatran; Network Meta-Analysis; Anticoagulants; Hemorrhage; Stroke; Rivaroxaban; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 37310479
DOI: 10.1007/s00228-023-03520-5 -
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