-
BMC Cardiovascular Disorders Feb 2020The optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to... (Meta-Analysis)
Meta-Analysis
Optimal duration of Vitamin K antagonists anticoagulant therapy after venous thromboembolism: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
The optimal duration of oral anticoagulant therapy for patients with venous thromboembolism (VTE) remains highly uncertain in clinical practice. It is essential to accurately assess the effect of anticoagulant therapy in reducing recurrent VTE against the risk of inducing major bleeding.
METHODS
Randomized controlled trials were identified by searching PubMed, Web of Science, Embase, and the Cochrane library, reporting rates of recurrent VTE and major bleeding in patients taking Vitamin K Antagonists (VKA) with VTE and comparing different durations.
RESULTS
Eleven RCTs with 3109 participants utilizing varied durations were included in the meta-analysis. Longer VKA therapy was associated with significantly lower rates of VTE recurrence compared with shorter duration of VKA therapy (OR 0.75, 95%CI 0.57-0.99), with significant difference noted in major bleeding risk (OR 2.31, 95%CI 1.17-4.56). During anticoagulation duration, patients treated by 6-month VKA had higher risk of major bleeding compared with 3-month VKA regimen (OR 33.45, 95%CI 2.00-559.67).
CONCLUSIONS
Regimen longer than 6 months did not show statistical elevation of major bleeding risk. VKA treatment strongly reduces the risk of recurrent VTE during anticoagulation therapy. The absolute risk of recurrent VTE declines over time while the risk for major bleeding after 6 months' treatment did not demonstrate a continuous significant increase with extended duration of VKA therapy.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Hemorrhage; Humans; Middle Aged; Randomized Controlled Trials as Topic; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K; Young Adult
PubMed: 32013892
DOI: 10.1186/s12872-020-01345-z -
JACC. Clinical Electrophysiology Dec 2019This study assessed the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) versus uninterrupted vitamin K antagonists (VKAs) for catheter ablation... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study assessed the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) versus uninterrupted vitamin K antagonists (VKAs) for catheter ablation (CA) of nonvalvular atrial fibrillation (NVAF) on 3 primary outcomes: major bleeding events (MBEs), minor bleeding events, and thromboembolic events (TEs). The secondary outcome was post-procedural silent cerebral infarction (SCI) as detected by brain cardiac magnetic resonance.
BACKGROUND
As a class, evidence of the benefits of DOACs versus VKAs during CA of AF is scant.
METHODS
A systematic review of Medline, Cochrane, and Embase was done to find all randomized controlled trials in which uninterrupted DOACs were compared against uninterrupted VKAs for CA of NVAF. A fixed-effect model was used, except when I was ≥25, in which case, a random effects model was used.
RESULTS
The benefit of uninterrupted DOACs over VKAs was analyzed from 6 randomized control trials that enrolled a total of 2,256 patients (male: 72.7%) with NVAF, finding significant benefit in MBEs (relative risk [RR]: 0.45; 95% confidence interval [CI]: 0.20 to 0.99; p = 0.05). No significant differences were found in minor bleeding events (RR: 1.12; 95% CI: 0.87 to 1.43; p = 0.39), TEs (RR: 0.75; 95% CI: 0.26 to 2.14; p = 0.59), or post-procedural SCI (RR: 1.09; 95% CI: 0.80 to 1.49; p = 0.58).
CONCLUSIONS
An uninterrupted DOACs strategy for CA of AF appears to be safer than uninterrupted VKAs with a decreased rate of major bleeding events. There are no significant differences among the other outcomes. DOACs should be offered as a first-line therapy to patients undergoing CA of AF, due to their lower risk of major bleeding events, ease of use, and fewer interactions.
Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Female; Hemorrhage; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Vitamin K
PubMed: 31857038
DOI: 10.1016/j.jacep.2019.08.010 -
Journal of Neurology Dec 2019To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.
METHODS
We conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.
RESULTS
We identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p < 0.0001, I = 92%, p < 0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p < 0.00001; I = 42%, p = 0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p < 0.00001; I = 65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p < 0.00001, I = 20%, p = 0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p < 0.00001, I = 71%, p = 0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.
CONCLUSION
This meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
Topics: Anticoagulants; Cerebral Hemorrhage; Hematoma; Humans; Vitamin K
PubMed: 31541341
DOI: 10.1007/s00415-019-09536-1 -
European Journal of Vascular and... May 2019The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE/BACKGROUND
The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer.
METHODS
A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method.
RESULTS
Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high.
CONCLUSION
Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.
Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Pulmonary Embolism; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K
PubMed: 31097186
DOI: 10.1016/j.ejvs.2018.11.004 -
PloS One 2019Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower...
Clinical presentation, diagnostic findings and management of cerebral ischemic events in patients on treatment with non-vitamin K antagonist oral anticoagulants - A systematic review.
BACKGROUND
Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower associated risk of intracranial hemorrhage compared to Vitamin K antagonists. Nevertheless, ischemic strokes also occur in patients who are being treated with NOAC. In those particular patients, knowledge about the underlying stroke etiology, clinical presentation, acute management, and complication rates is scarce.
OBJECTIVE
Systematic literature review to provide a comprehensive clinical overview in terms of presentation, laboratory, imaging parameters and outcomes of patients suffering from acute cerebral ischemic events (i.e. TIA and acute ischemic stroke) while on treatment with a NOAC. Only if available, comparison to VKA is presented which was not the primary focus of this analysis.
DATA SOURCES
PubMed/MEDLINE, Scopus and EMBASE from January 1, 2006, to November 20, 2018.
STUDY ELIGIBILITY CRITERIA
52 studies providing detailed information on a total of 12247 patients were included. We excluded case reports and case series with less than five patients.
STUDY APPRAISAL AND SYNTHESIS METHOD
We systematically assessed study quality using a bias tool and pooled consistent data.
RESULTS
Existing data indicates milder stroke severity and smaller infarct size of acute ischemic stroke on treatment with NOAC compared to stroke occurrence on Vitamin K antagonists (VKA). Established risk factors for ischemic events also play a role in stroke while on NOACs, albeit the underlying etiology remains poorly understood. Intravenous thrombolysis and endovascular therapy seem to be safe and effective, but patient selection for recanalization therapies is challenging.
LIMITATIONS
Limited quality of published data, duplicate cases, statistical issues of data pooling, possible incomplete retrieval of identified research and reporting bias might have limited our findings.
CONCLUSIONS
Acute ischemic events despite treatment with NOAC therapy are insufficiently investigated.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO: CRD42018074853.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Brain Ischemia; Endovascular Procedures; Female; Humans; Ischemic Attack, Transient; Male; Reperfusion; Risk Factors; Stroke; Thrombolytic Therapy; Vitamin K
PubMed: 30925155
DOI: 10.1371/journal.pone.0213379 -
Pharmacological Research May 2019The aim of this study was to systematically review published network meta-analyses (NMAs) that compare venous thromboembolism (VTE) treatments. A systematic literature... (Meta-Analysis)
Meta-Analysis
The aim of this study was to systematically review published network meta-analyses (NMAs) that compare venous thromboembolism (VTE) treatments. A systematic literature search (in MEDLINE, Embase, and Cochrane Database of Systematic Reviews through September 2017) was conducted to identify NMAs that compared the safety and efficacy of direct oral anticoagulants (DOACs) for the treatment of VTE in the acute and extended treatment settings. The NMAs included randomized controlled trials comparing multiple DOACs, low-molecular weight heparin, unfractionated heparin, and vitamin K antagonists (VKAs). The quality of the NMA results were evaluated using the Grading of Recommendations and Evaluation (GRADE) assessment. The SLR identified 294 records and nine NMAs (68 trials). Among the NMAs, three evaluated the acute treatment setting, five the extended, and one in both treatment settings. The NMAs showed a significant reduction in major bleeding and clinically relevant bleeding (CRB) with apixaban compared to other DOACs. Major bleeding with apixaban was reduced compared to dabigatran, edoxaban, and fondaparinux-VKA combination in all comparisons in the acute setting (range of effect estimates: 0.30-0.43). CRB was reduced with apixaban compared to dabigatran, edoxaban, and rivaroxaban in the acute and extended settings (range of effect estimates: 0.23-0.72). No significant differences were seen in efficacy outcomes between the DOACs. This SLR of NMAs systematically collected all indirect evidence of the impact of apixaban compared to other anticoagulants in patients with VTE. In the absence of head-to-head trials, well-conducted NMAs provide the best evidence.
Topics: Anticoagulants; Hemorrhage; Heparin; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thromboembolism; Vitamin K
PubMed: 30905806
DOI: 10.1016/j.phrs.2019.03.017 -
PloS One 2019Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT.
METHODS
We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications.
RESULTS
We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42-0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40-0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11-2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54-1.01). Both DOAC (HR 0.42; 95% CI 0.29-0.61) and LMWH (HR 0.57; 95% CI 0.44-0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding.
CONCLUSIONS
DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.
Topics: Acute Disease; Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Neoplasms; Network Meta-Analysis; Recurrence; Risk Factors; Safety; Secondary Prevention; Venous Thromboembolism; Vitamin K
PubMed: 30897142
DOI: 10.1371/journal.pone.0213940 -
Blood Advances Mar 2019Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically... (Meta-Analysis)
Meta-Analysis Review
Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation.
Topics: Anticoagulants; Hemorrhage; Humans; International Normalized Ratio; Risk Assessment; Vitamin K; Vitamin K Deficiency
PubMed: 30850385
DOI: 10.1182/bloodadvances.2018025163 -
The American Journal of Medicine Jun 2019Vitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear...
BACKGROUND
Vitamin K antagonists (VKA) are the most widely used anticoagulants, and bridging is commonly administered during periprocedural VKA interruption. Given the unclear benefits and risks of periprocedural bridging in patients with previous venous thromboembolism, we aimed to assess recurrent venous thromboembolism and bleeding outcomes with and without bridging in this population.
METHODS
We performed a systematic review searching the PubMed and Embase databases from inception to December 7, 2017 for randomized and nonrandomized studies that included adults with previous venous thromboembolism requiring VKA interruption to undergo an elective procedure, and that reported venous thromboembolism or bleeding outcomes. Quality of evidence was graded by consensus.
RESULTS
We included 28 cohort studies (20 being single-arm cohorts) with, overall, 6915 procedures for analysis. In 27 studies reporting perioperative venous thromboembolism outcomes, the pooled incidence of recurrent venous thromboembolism with bridging was 0.7% (95% confidence interval [CI], 0.4%-1.2%) and 0.5% (95% CI, 0.3%-0.8%) without bridging. Eighteen studies reported major or nonmajor bleeding outcomes. The pooled incidence of any bleeding was 3.9% (95% CI, 2.0%-7.4%) with bridging and 0.4% (95% CI, 0.1%-1.7%) without bridging. In bridged patients at high thromboembolic risk, the pooled incidence for venous thromboembolism was 0.8% (95% CI, 0.3%-2.5%) and 7.5% (95% CI, 3.1%-17.4%) for any bleeding. Quality of available evidence was very low, primarily due to a high risk of bias of included studies.
CONCLUSIONS
Periprocedural bridging increases the risk of bleeding compared with VKA interruption without bridging, without a significant difference in periprocedural venous thromboembolism rates.
Topics: Anticoagulants; Hemorrhage; Humans; Venous Thromboembolism; Vitamin K
PubMed: 30659809
DOI: 10.1016/j.amjmed.2019.01.004 -
Medicine Dec 2018Vitamin K antagonists (VKAs) may have potential antitumor effects in prostate cancer. However, the findings of observational studies are inconsistent. The purpose of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin K antagonists (VKAs) may have potential antitumor effects in prostate cancer. However, the findings of observational studies are inconsistent. The purpose of the present study was to estimate the quantitative association between VKAs use and prostate cancer risk by combining the results of all eligible observational studies.
METHODS
PubMed and Web of Science database were searched from inception until May, 2018. A DerSimonian random-effects model was used to combine the studies. Study heterogeneity was measured using the chi-squared and I statistics.
RESULTS
Six eligible studies were eventually included in our meta-analysis. There was an inverse but not statistically significant association between ever use of VKAs and the risk of prostate cancer (relative risk [RR] 0.84, 95% confidence interval [CI] 0.70-1.01, P = .063) with large heterogeneity across studies (P < .001 for heterogeneity, I = 94.6%). When analysis restricted to long term of VKAs user (>3 years), the pooled risk estimate was 0.83 (0.77-0.90) without obvious heterogeneity (P = .597, I = 0.0%).
CONCLUSION
This meta-analysis indicates that VKAs use may be associated with a decreased risk of prostate cancer, especially in long-term users.
Topics: Humans; Male; Observational Studies as Topic; Prostatic Neoplasms; Risk; Vitamin K
PubMed: 30544443
DOI: 10.1097/MD.0000000000013489