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Clinical Cardiology Oct 2022In the past decade, direct oral anticoagulants (DOACs) have proven to be the best option for patients with nonvalvular atrial fibrillation. Nevertheless, evidence for... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of efficacy and safety between VKAs and DOACs in patients with atrial fibrillation after transcatheter aortic valve replacement: A systematic review and meta-analysis.
In the past decade, direct oral anticoagulants (DOACs) have proven to be the best option for patients with nonvalvular atrial fibrillation. Nevertheless, evidence for the use of DOACs for anticoagulation in valvular atrial fibrillation, particularly after aortic valve replacement, remains inadequate. Thus, we conducted a meta-analysis to compare the efficacy and safety of vitamin K antagonists (VKAs) and DOACs in patients with atrial fibrillation after transcatheter aortic valve replacement (TAVR). We conducted a comprehensive search of online databases, and 11 studies were included in the final analysis. The primary endpoint was all-cause mortality. Secondary endpoints included stroke and cardiovascular death. The safe endpoint is major and/or life-threatening bleeding. Subgroup analysis was conducted according to the different follow-up time of each study. Random-effects models were used for all outcomes. Statistical heterogeneity was assessed using χ tests and quantified using I statistics. Patients in the DOACs group had a significantly lower risk of all-cause mortality compared with patients in the VKAs group (relative risk [RR]: 1.20, 95% confidence interval [CI]: 1.01-1.43, p = .04). This benefit may be greater with longer follow-up. In a subgroup analysis based on the length of follow-up, a significantly lower risk of all-cause mortality was found in the DOACs group in the subgroup with a follow-up time of >12 months (RR: 1.50, 95% CI: 1.07-2.09, p = .001). There were no significant differences between the two groups in cardiovascular death, stroke, and major and/or life-threatening bleeding. For patients with atrial fibrillation after TAVR, the use of DOACs may be superior to VKAs, and the benefit may be greater with longer follow-up. The anticoagulant strategy for atrial fibrillation after TAVR is a valuable direction for future research.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Hemorrhage; Stroke; Transcatheter Aortic Valve Replacement; Vitamin K
PubMed: 36030549
DOI: 10.1002/clc.23909 -
PloS One 2015Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.
OBJECTIVE
A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.
DATA SOURCES
MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.
STUDY SELECTION
Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.
DATA EXTRACTION
Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.
DATA SYNTHESIS
Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.
CONCLUSIONS
VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences.
Topics: Anticoagulants; Aspirin; Data Collection; Drug Administration Schedule; Female; Hemorrhage; Humans; Male; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Sex Factors; Thromboembolism; Treatment Outcome; Vitamin K; Warfarin
PubMed: 26587983
DOI: 10.1371/journal.pone.0143252 -
Renal Failure Dec 2024This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis.
METHODS
All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible.
RESULTS
Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes.
CONCLUSIONS
Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.
Topics: Humans; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Renal Dialysis; Vitamin K
PubMed: 38770962
DOI: 10.1080/0886022X.2024.2349114 -
Journal of Thrombosis and Haemostasis :... 2014New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have... (Meta-Analysis)
Meta-Analysis Review
Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.
INTRODUCTION
New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models.
RESULTS
Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban.
CONCLUSIONS
NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk Factors; Rivaroxaban; Thiazoles; Thiophenes; Treatment Outcome; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 24330006
DOI: 10.1111/jth.12485 -
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 Cochrane Database of Systematic... Aug 2014Currently, the most frequently used secondary treatment for patients with venous thromboembolism (VTE) consists of vitamin K antagonists (VKA) targeted at an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Currently, the most frequently used secondary treatment for patients with venous thromboembolism (VTE) consists of vitamin K antagonists (VKA) targeted at an international normalized ratio (INR) of 2.5 (range 2.0 to 3.0). However, based on the continuing risk of bleeding and uncertainty regarding the risk of recurrent VTE, discussion on the proper duration of treatment with VKA for these patients is ongoing. Several studies have compared the risks and benefits of different durations of VKA in patients with VTE. This is the third update of a review first published in 2000.
OBJECTIVES
To evaluate the efficacy and safety of different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 9.
SELECTION CRITERIA
Randomized controlled clinical trials comparing different durations of treatment with vitamin K antagonists in patients with symptomatic venous thromboembolism.
DATA COLLECTION AND ANALYSIS
Three review authors (SM, MP, and BH) extracted the data and assessed the quality of the trials independently.
MAIN RESULTS
Eleven studies with a total of 3716 participants were included. A consistent and strong reduction in the risk of recurrent venous thromboembolic events was observed during prolonged treatment with VKA (risk ratio (RR) 0.20, 95% confidence interval (CI) 0.11 to 0.38) independent of the period elapsed since the index thrombotic event. A statistically significant "rebound" phenomenon (ie, an excess of recurrences shortly after cessation of prolonged treatment) was not found (RR 1.28, 95% CI 0.97 to 1.70). In addition, a substantial increase in bleeding complications was observed for patients receiving prolonged treatment during the entire period after randomization (RR 2.60, 95% CI 1.51 to 4.49). No reduction in mortality was noted during the entire study period (RR 0.89, 95% CI 0.66 to 1.21, P = 0.46).
AUTHORS' CONCLUSIONS
In conclusion, this review shows that treatment with VKA strongly reduces the risk of recurrent VTE for as long as they are used. However, the absolute risk of recurrent VTE declines over time, although the risk for major bleeding remains. Thus, the efficacy of VKA administration decreases over time since the index event.
Topics: Anticoagulants; Drug Administration Schedule; Hemorrhage; Humans; International Normalized Ratio; Randomized Controlled Trials as Topic; Secondary Prevention; Thromboembolism; Time Factors; Venous Thrombosis; Vitamin K
PubMed: 25092359
DOI: 10.1002/14651858.CD001367.pub3 -
Journal of General Internal Medicine Feb 2019Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin K antagonist (VKA) anticoagulant use is suspected to increase the risk of bone fracture through inhibition of vitamin K-dependent cofactors of bone formation, an effect not seen with non-vitamin K antagonist oral anticoagulants (NOACs). The purpose of our systematic review and meta-analysis is to investigate the association between VKA use and fracture.
METHODS
We searched PubMed, EMBASE, and Cochrane Library for studies analyzing fracture in adults using VKAs versus controls. Two authors independently reviewed articles. We assessed for risk of bias using the Newcastle-Ottawa Quality Assessment Scale and the Cochrane Risk of Bias Tool and calculated pooled effects using random effects models.
RESULTS
We included 23 articles (22 observational studies and 1 randomized controlled trial), studying 1,121,582 subjects. There was no increased odds of fracture in VKA users versus controls (pooled OR 1.01, 95% CI 0.89, 1.14) or in VKA users versus NOAC users (pooled OR 0.95, 95% CI 0.78, 1.15). Subjects using a VKA for 1 year or longer did not have increased odds of fracture (pooled OR 1.07, 95% CI 0.90, 1.27). Compared to controls, there was increased odds of fracture in women (pooled OR 1.11, 95% CI 1.02, 1.21) and older VKA users (≥ 65) (pooled OR 1.07, 95% CI 1.01, 1.14).
DISCUSSION
We found no increase in odds of fracture in VKA users versus controls or NOAC users. There was a small increase in odds of fracture among female and elderly VKA users, which may not be clinically important when accounting for other considerations in choosing an anticoagulant. Our findings suggest that, when anticoagulation is necessary, fracture risk should not be a major consideration in choice of an agent. Future studies directly comparing VKA to NOAC users and studies with longer duration of VKA use may be needed.
Topics: Administration, Oral; Anticoagulants; Fractures, Bone; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Vitamin K
PubMed: 30511289
DOI: 10.1007/s11606-018-4758-2 -
Current Problems in Cardiology Aug 2023
Meta-Analysis Review
Head-to-head Comparison Between Direct Oral Anticoagulants and Vitamin K Antagonists for Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-Analysis.
Topics: Humans; Hypertension, Pulmonary; Anticoagulants; Fibrinolytic Agents; Vitamin K; Administration, Oral; Atrial Fibrillation
PubMed: 35500739
DOI: 10.1016/j.cpcardiol.2022.101232 -
Journal of the Formosan Medical... May 2024The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF.
METHODS
An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022.
RESULTS
Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban.
CONCLUSION
Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.
Topics: Humans; Atrial Fibrillation; Warfarin; Anticoagulants; Network Meta-Analysis; Dabigatran; Administration, Oral; Hemorrhage; Stroke; Rivaroxaban; Vitamin K
PubMed: 37996330
DOI: 10.1016/j.jfma.2023.10.014 -
Annals of Internal Medicine Feb 2007New treatments are available for treatment of venous thromboembolism. (Review)
Review
BACKGROUND
New treatments are available for treatment of venous thromboembolism.
PURPOSE
To review the evidence on the efficacy of interventions for treatment of deep venous thrombosis (DVT) and pulmonary embolism.
DATA SOURCES
MEDLINE, MICROMEDEX, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews from the 1950s through June 2006.
STUDY SELECTION
Randomized, controlled trials; systematic reviews of trials; and observational studies; all restricted to English-language articles.
DATA EXTRACTION
Paired reviewers assessed study quality and abstracted data. The authors pooled results about optimal duration of anticoagulation.
DATA SYNTHESIS
This review includes 101 articles. Low-molecular-weight heparin (LMWH) is modestly superior to unfractionated heparin at preventing recurrent DVT and is at least as effective as unfractionated heparin for treatment of pulmonary embolism. Outpatient treatment of venous thromboembolism is likely to be effective and safe in carefully chosen patients, with appropriate services available. Inpatient or outpatient use of LMWH is cost-saving or cost-effective compared with unfractionated heparin. In observational studies, catheter-directed thrombolysis safely restored vein patency in select patients. Moderately strong evidence supports early use of compression stockings to reduce postthrombotic syndrome. Limited evidence suggests that vena cava filters are only modestly efficacious for prevention of pulmonary embolism. Conventional-intensity oral anticoagulation beyond 12 months may be optimal for patients with unprovoked venous thromboembolism, although patients with transient risk factors benefit little from more than 3 months of therapy. High-quality trials support use of LMWH in place of oral anticoagulation, particularly in patients with cancer. Little evidence is available to guide treatment of venous thromboembolism during pregnancy.
LIMITATIONS
The authors could not address all management questions, and excluded non-English-language literature.
CONCLUSIONS
The strength of evidence varies across the study questions but generally is strong.
Topics: Ambulatory Care; Anticoagulants; Cost-Benefit Analysis; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Pregnancy; Pregnancy Complications, Hematologic; Pulmonary Embolism; Secondary Prevention; Stockings, Compression; Thromboembolism; Thrombolytic Therapy; Vena Cava Filters; Venous Thrombosis; Vitamin K
PubMed: 17261856
DOI: 10.7326/0003-4819-146-3-200702060-00150