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ESC Heart Failure Oct 2022Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a... (Meta-Analysis)
Meta-Analysis
AIMS
Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT.
METHODS AND RESULTS
We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed.
CONCLUSIONS
Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.
Topics: Humans; Vitamin K; Anticoagulants; Thrombosis; Hemorrhage; Stroke; Embolism
PubMed: 35894752
DOI: 10.1002/ehf2.14084 -
Therapeutic Advances in Cardiovascular... 2022Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF)... (Meta-Analysis)
Meta-Analysis
AIMS
Oral anticoagulation with direct oral anticoagulants (DOAC) could provide an alternative to vitamin K antagonists (VKA) for patients with atrial fibrillation (AF) undergoing bioprosthetic heart valve replacement or valve repair.
METHODS AND RESULTS
The aim of this meta-analysis was to review the safety and efficacy of DOAC in patients with surgical implanted bioprosthetic heart valves or valve repairs and AF including data from six clinical trials with a total of 1,857 patients. The efficacy and safety data of DOAC and VKA were pooled to perform random-effects meta-analyses using the Mantel-Haenszel method with pooled risk ratios (RR) and 95% confidence interval (CI). A trial sequential analysis (TSA) was performed to assess statistical robustness. Death caused by cardiovascular cause or thromboembolic events were comparable (RR 0.67, 95% CI: 0.42-1.08; = 0.10) as DOAC significantly reduced the risk for major bleeding (RR 0.55, 95% CI: 0.35-0.88; = 0.01) and thromboembolic stroke or systemic embolism rates (RR 0.54, 95% CI: 0.32-0.90; = 0.02). Rates for intracranial bleeding and hemorrhagic stroke (RR 0.27, 95% CI: 0.07-0.99; = 0.05) show a trend toward fewer events in the DOAC group. Outcomes for major or minor bleeding events and all-cause mortality were comparable for DOAC and VKA.
CONCLUSION
Cumulative data analysis reveals that DOAC may provide an effective and safe alternative to VKA in patients with AF after surgically implanted bioprosthetic heart valves or repair with AF. Within a relatively heterogeneous study population, this meta-analysis shows a risk reduction of major bleedings and thromboembolic stroke or systemic embolisms for DOAC.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Hemorrhage; Humans; Stroke; Thromboembolism
PubMed: 35481366
DOI: 10.1177/17539447221093963 -
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 -
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 -
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 -
BMJ Open Jun 2014To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0-3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy.
RESULTS
For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA.
CONCLUSIONS
Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more strokes compared with anticoagulant drugs without any reduction in bleeding risk. To fully elucidate the comparative benefits and harms of antithrombotic agents across the various subpopulations, rigorously conducted comparative studies or network meta-regression analyses of patient-level data are required.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO registry-CRD42012002721.
Topics: Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Severity of Illness Index; Stroke
PubMed: 24889848
DOI: 10.1136/bmjopen-2013-004301 -
Journal of Cardiovascular Medicine... Dec 2015Atrial fibrillation is the most common supraventricular arrhythmia. Its prevalence increases with age and preferentially affects male patients. Over 75 years of age,... (Review)
Review
Atrial fibrillation is the most common supraventricular arrhythmia. Its prevalence increases with age and preferentially affects male patients. Over 75 years of age, however, female patients being more prevalent, the absolute number of patients affected is similar between sexes. Despite this, few data are available in the literature concerning sex-related differences in atrial fibrillation patients. The present systematic review therefore considers comorbidities, referring symptoms, quality of life, pharmacological approaches and trans-catheter ablation in female rather than in male atrial fibrillation patients in search of parameters that may have an impact on the treatment outcome. In brief, female atrial fibrillation patients more commonly present comorbidities, leading to a higher prevalence of persistent atrial fibrillation; moreover, they refer to hospital care later and with a longer disease history. Atrial fibrillation symptoms relate to low quality of life in female patients; in fact, atrial fibrillation paroxysm usually presents higher heart rate, leading to preferentially adopt a rate rather than a rhythm-control strategy. Female atrial fibrillation patients present an increased risk of stroke, worsened by the lower oral anticoagulant prescription rate related to the concomitant higher haemorrhagic risk profile. Trans-catheter ablation is under-used in female patients and, on the contrary, they are more commonly affected by anti-arrhythmic drug side effects.
Topics: Anticoagulants; Atrial Fibrillation; Catheter Ablation; Comorbidity; Female; Hemorrhage; Humans; Quality of Life; Sex Distribution; Sex Factors; Thromboembolism
PubMed: 25806470
DOI: 10.2459/JCM.0000000000000239 -
BMJ (Clinical Research Ed.) Aug 2013To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis.
OBJECTIVE
To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.
REVIEW METHODS
Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.
RESULTS
12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.
CONCLUSIONS
All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Topics: Anticoagulants; Aspirin; Benzimidazoles; Dabigatran; Hemorrhage; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 23996149
DOI: 10.1136/bmj.f5133 -
Drugs in R&D Dec 2020Nimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral...
Nimodipine has been shown to improve outcomes following aneurysmal subarachnoid hemorrhage. Guidelines recommend that all patients receive a fixed dose of oral nimodipine for 21 days. However, pharmacokinetic studies have suggested variability of nimodipine pharmacokinetics in subarachnoid hemorrhage and in other patient populations. The clinical relevance of such variability is unknown. Therefore, the objective of the present review is, first, to conduct a literature review and summarize nimodipine pharmacokinetic data and sources of variability in various patient groups. Second, to determine if there is any evidence reporting an association between nimodipine exposure and clinical outcomes in patients with subarachnoid hemorrhage. A systematic literature search was performed in MEDLINE and EMBASE. The following keywords were used: ("nimodipine" OR "nymalize" OR "nimotop") AND ("pharmacokinetic*", OR "PK"). The search results were limited to English language and human studies. A large interpatient variability in nimodipine pharmacokinetics has been reported. Patient-specific factors that had an influence on pharmacokinetic parameters are age, comorbidities, variabilities in metabolism due to genetic polymorphism and co-administered medications, as well as nimodipine administration technique. The association between nimodipine exposure and clinical outcomes remains unclear and data available are too scarce to reach a firm conclusion. Here, we present a narrative review with a systematic literature search discussing nimodipine pharmacokinetic variability in various patient populations. It is not clear if minimal or lack of systemic exposure to nimodipine denies its benefit and contributes to worsening outcomes in patients with subarachnoid hemorrhage. Further studies are needed to determine if such an association exists.
Topics: Animals; Biological Variation, Population; Drug Interactions; Epidemiologic Factors; Humans; Nimodipine; Subarachnoid Hemorrhage; Treatment Outcome; Vasodilator Agents
PubMed: 32902829
DOI: 10.1007/s40268-020-00322-3 -
Journal of Thrombosis and Haemostasis :... Jul 2018Essentials Risk of intracranial hemorrhage (ICH) may differ between direct oral anticoagulants (DOACs). We compared the risk of ICH between DOACs using network... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Essentials Risk of intracranial hemorrhage (ICH) may differ between direct oral anticoagulants (DOACs). We compared the risk of ICH between DOACs using network meta-analysis. Dabigatran 110 mg and 150 mg were safer than rivaroxaban on Bayesian analysis. Dabigatran 110 mg ranked as the safest DOAC while rivaroxaban ranked last.
SUMMARY
Background The comparative risk of intracranial hemorrhage (ICH) among direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban and edoxaban) remains unclear. Objective To determine the difference in risk of ICH between DOACs Methods Seventeen randomized controlled trials (RCTs) were selected using PubMed/MEDLINE, EMBASE and CENTRAL (Inception, 31 December 2017). Estimates were reported as odds ratio (OR) with 95% credible interval (CR.I) in Bayesian network meta-analysis (NMA), and OR with 95% confidence interval (CI) in traditional meta-analyses. Relative ranking probability of each group was generated based on surface under the cumulative ranking curve (SUCRA). Results In NMA of 116 618 patients from 17 RCTs (apixaban = 19 495 patients, rivaroxaban = 14 157 patients, dabigatran = 16 074 patients, edoxaban = 11 652 patients, and comparator = 55 315 patients), all DOACs were safer than warfarin for risk of ICH. Dabigatran 110 mg ranked as the safest drug (SUCRA, 0.85) and reduced the risk of ICH by 56% compared to rivaroxaban (OR, 0.44; 95% Cr.I, 0.22-0.82). Pairwise meta-analysis validated these findings, showing that DOACs were safer than warfarin (OR, 0.46; 95% CI, 0.35-0.59). Subgroup analysis showed that the benefit was present when DOACs were used in non-valvular atrial fibrillation (NVAF) (OR, 0.51; 95% CI, 0.38-0.68) or venous thromboembolism (VTE) (OR, 0.32; 95% CI, 0.18-0.58). Conclusion Dabigatran 110 mg may be the safest choice among any anticoagulant regarding risk of ICH. Both dabigatran 110 mg and 150 mg were safer than rivaroxaban.
Topics: Administration, Oral; Antithrombins; Bayes Theorem; Dabigatran; Factor Xa Inhibitors; Humans; Intracranial Hemorrhages; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles; Treatment Outcome
PubMed: 29723935
DOI: 10.1111/jth.14131