Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation

2015 ◽  
Vol 114 (10) ◽  
pp. 768-777 ◽  
Author(s):  
Emilie Belley-Cote ◽  
Hasib Hanif ◽  
Frederick D’Aragon ◽  
John Eikelboom ◽  
Jeffrey Anderson ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Vitamin K Antagonist ◽  
Random Effects Model ◽  
Thromboembolic Events ◽  
Clinical Algorithm ◽  
Significant Difference ◽  
Clinical Algorithms

SummaryVariability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (pri-mary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our meta-analysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95 % confidence interval [CI] 0.54–1.34; heterogeneity X2=4.46, p=0.35, I2=10 %). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotype-guided group (mean difference (MD) 4.31 %; 95 % CI 0.35, 8.26; heterogeneity X2=43.31, p< 0.001, I2=79 %). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when geno-type-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41 %; 95 % CI 3.50,13.31; heterogeneity X2=15.18, p=0.01, I2=67 %) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD –0.29 %; 95 % CI –2.48,1.90; heterogeneity X2=1.53, p=0.68, I2=0 %; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms.

scholarly journals Uninterrupted or Minimally Interrupted Direct Oral Anticoagulant Therapy is a Safe Alternative to Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation: An Updated Meta-Analysis

2020 ◽  
Vol 9 (10) ◽  
pp. 3073
Author(s):  
Máté Ottóffy ◽  
Péter Mátrai ◽  
Nelli Farkas ◽  
Péter Hegyi ◽  
László Czopf ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Meta Analysis ◽  
Thromboembolic Events ◽  
Direct Oral Anticoagulant ◽  
Significant Difference ◽  
Life Threatening

Adequate anticoagulation during catheter ablation (CA) for atrial fibrillation (AF) is crucial for the prevention of both thromboembolic events and life-threatening bleeding. The purpose of this updated meta-analysis is to compare the safety and efficacy of uninterrupted and minimally interrupted periprocedural direct oral anticoagulant (DOAC) protocols and uninterrupted vitamin K antagonist (VKA) therapy in patients undergoing CA for AF based on the latest evidence. Randomized controlled trials, prospective observational studies, and retrospective registries comparing DOACs to VKAs were identified in multiple databases (Embase, MEDLINE via PubMed, CENTRAL, and Scopus). The primary outcomes were stroke or transient ischemic attack (TIA), major bleeding, and net clinical benefit. Forty-two studies with a total of 22,715 patients were included in the final analysis. The occurrence of major bleeding was significantly lower in patients assigned to uninterrupted DOAC treatment compared to VKAs (pooled odds ratio (POR): 0.71, confidence interval (CI): 0.51–0.99). The pooled analysis of both uninterrupted and minimally interrupted DOAC groups also showed significant reduction in major bleeding events (POR: 0.70, CI: 0.53–0.93). The incidence of thromboembolic events was low, with no significant difference between groups. This updated meta-analysis showed that DOAC therapy is as effective as VKA in preventing stroke and TIA. Minimally interrupted DOAC therapy is a non-inferior periprocedural anticoagulation strategy; however, uninterrupted DOAC therapy showed superiority compared to VKA with regard to major, life-threatening bleeding. Based on our in-depth analysis, we conclude that both DOAC strategies are equally safe and preferable alternatives to VKAs in patients undergoing CA for AF.

Abstract 15090: Direct Oral Anticoagulation vs Vitamin K Antagonist in Atrial Fibrillation With Liver Disease: A Systematic Review and Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mahmoud El Iskandarani ◽  
Islam Shatla ◽  
Muhammad Khalid ◽  
Bara El Kurdi ◽  
Timir Paul ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Ischemic Stroke ◽  
Liver Disease ◽  
Vitamin K ◽  
Major Bleeding ◽  
Lower Risk ◽  
Meta Analysis ◽  
Vitamin K Antagonist ◽  
All Cause Mortality

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.

scholarly journals Prevention of Stroke in Atrial Fibrillation After Coronary Stenting

Stroke ◽  
2019 ◽  
Vol 50 (8) ◽  
pp. 2125-2132
Author(s):  
Leonardo Knijnik ◽  
Manuel Rivera ◽  
Vanessa Blumer ◽  
Rhanderson Cardoso ◽  
Amanda Fernandes ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antiplatelet Therapy ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Observational Studies ◽  
Meta Analysis ◽  
Vitamin K Antagonist ◽  
Coronary Stenting ◽  
Direct Acting

Background and Purpose— The optimal antithrombotic strategy to balance thromboembolic and bleeding events, especially acute stroke, for patients with atrial fibrillation following coronary stenting remains a matter of debate. We conducted a network meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in atrial fibrillation after coronary stenting. Methods— PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials and observational studies of patients with atrial fibrillation after coronary stenting. The outcomes of interest were stroke, myocardial infarction, major adverse cardiac events, mortality, and major bleeding. A network meta-analysis was performed comparing the available antithrombotic regimens in the literature. Results— Three randomized and 15 observational studies were included, with a total of 23 478 participants. Median follow-up was 2 years. Network meta-analysis demonstrated that vitamin K antagonist plus single antiplatelet therapy or direct-acting oral anticoagulant plus single antiplatelet therapy were the most effective regimens in preventing stroke. Direct-acting oral anticoagulant regimens were associated with lower major bleeding rates than vitamin K antagonist regimens. Regimens with dual antiplatelet therapy were associated with lower rates of myocardial infarction. Vitamin K antagonist plus dual antiplatelet therapy was associated with a lower mortality and low-dose direct-acting oral anticoagulants with decreased major cardiovascular adverse events. Conclusions— Direct-acting oral anticoagulant regimens were associated with less major bleeding and major cardiovascular adverse events, but vitamin K antagonists were associated with decreased mortality and stroke. These results suggest that the decision of antithrombotic therapy in patients with atrial fibrillation after percutaneous coronary intervention needs to be individualized.

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: An updated pairwise and network meta-analysis of randomized trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14692-e14692
Author(s):  
Shima Sidahmed ◽  
Ahmed Abdalla ◽  
Babikir Kheiri ◽  
Areeg Bala ◽  
Mohammed Salih ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K ◽  
Major Bleeding ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Number Needed To Treat ◽  
Cancer Type ◽  
Significant Difference ◽  
All Cause Mortality

e14692 Background: Cancer-associated venous thromboembolism (VTE) is common. Although low molecular weight heparin (LMWH) is the standard therapy in this setting, little is known with regard to non-vitamin K antagonist oral anticoagulants (NOACs). Therefore, we thought about evaluating the safety and efficacy of various anticoagulants in this vulnerable population. Methods: Electronic database search was conducted to identify randomized clinical trials (RCTs) that compared LMWH, NOACs, and/or vitamin-K-antagonists (VKA) in cancer patients. We performed frequentist direct and Bayesian network meta-analysis using random-effects model to calculate odds ratios (ORs), 95% confidence intervals (CIs), and 95% credible intervals (CrIs). The primary outcome was VTE (pulmonary embolism and deep-vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. Results: We identified 13 RCTs with 6,595 total patients (mean age 62.4 ± 12.2; 50.4% female; 17.7% hematological malignancies; and 6 months median follow-up). The most common cancer type was colorectal and 48% of the population had metastatic cancer at baseline. NOACs were associated with significantly reduced VTE recurrence compared with VKA (OR = 0.58; 95% CI = 0.40-0.83; P < 0.01; number needed to treat [NNT] = 40) and LMWH (OR = 0.46; 95% CI = 0.25-0.85; P = 0.01; NNT = 20). LMHW was associated with significantly reduced VTE recurrence compared with VKA (OR = 0.52; 95% CI = 0.39-0.71; P < 0.01; NNT = 18). NOACs were associated with significantly reduced major bleeding compared with VKA (OR = 0.56; 95% CI = 0.35-0.91; P = 0.02; NNT = 64). There was no significant difference identified between the anticoagulant groups in regard to all-cause mortality. Conclusions: Among cancer patients with VTE, NOACs were associated with significantly reduced VTE recurrence compared to LMWH and VKA, and significantly reduced major bleeding compared with VKA. LMWH was associated with significantly reduced VTE recurrence compared with VKA.

Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials

EP Europace ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Tatjana S Potpara ◽  
Nebojsa Mujovic ◽  
Marco Proietti ◽  
Nikolaos Dagres ◽  
Gerhard Hindricks ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Stent Thrombosis ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonist ◽  
Full Dose ◽  
Pooled Data ◽  
Percutaneous Coronary

Abstract Aims Recently, three randomized trials reported that dual antithrombotic treatments (DATs) including non-vitamin K antagonist oral anticoagulants (NOACs) and a P2Y12 inhibitor without aspirin were associated with significantly less bleeding than vitamin K antagonist (VKA)-based triple antithrombotic therapy (TAT) in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We conducted an analysis of pooled data from these trials. Methods and results A meta-analysis of the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials considering major bleeding [International Society on Thrombosis and Haemostasis (ISTH) and Thrombolysis in Myocardial Infarction], clinically relevant non-major bleeding, all-cause/cardiovascular death, stroke, myocardial infarction (MI), and stent thrombosis. Treatment effect is reported as odds ratio (OR) and 95% confidence interval. Among 9463 patients (53% with ACS), DAT regimens were associated with significantly less bleeding than TAT (OR 0.598, 0.491 −0.727; P &lt; 0.001 for ISTH major bleeding), as were NOAC-based vs. VKA-based regimens (OR 0.577, 0.477 −0.698; P &lt; 0.001). Stroke and mortality rates were similar, but there was statistically non-significant trend towards greater risk of MI (OR 1.211, 0.955 −1.535; P = 0.115) and significantly higher risk for stent thrombosis (OR 1.672, 1.022 −2.733, P = 0.041) with DAT vs. TAT (but not NOAC- vs. VKA-based regimens). This was mainly driven by Dabigatran 110 mg; the trends were lower with full-dose NOAC or Rivaroxaban 15 mg-based DATs. Conclusion Our findings support the use of full-dose NOAC (Apixaban 5 mg, Dabigatran 150 mg) or Rivaroxaban 15 mg-based treatments in most AF patients with ACS or undergoing PCI. Notwithstanding the better safety of DAT, an initial course of NOAC-based TAT may be desirable in most AF patients.

scholarly journals Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation and Cancer: Meta-Analysis of Observational Studies

2021 ◽  
Author(s):  
Bo Cao ◽  
Xiaobo Hu ◽  
Min Chen ◽  
Mingfeng Shen ◽  
Lan Xu
Keyword(s):  
Gastrointestinal Bleeding ◽  
Ischaemic Stroke ◽  
Vitamin K ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Efficacy And Safety ◽  
Systemic Embolism

Abstract BackgroundEvidence on the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer is rather limited, so we performed this meta-analysis to compare the efficacy and safety of NOACs with vitamin K antagonists (VKAs) in real-world patients with AF and cancer. MethodsThe PubMed and Embase databases were searched up to June 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) using a random-effects model. ResultsA total of five observational studies involving 232,234 cancer patients with AF were included. Compared with VKAs, use of NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.79; 95% CI 0.69-0.90), ischaemic stroke (RR, 0.82; 95% CI, 0.72-0.93), venous thromboembolism (VTE) (RR, 0.28; 95% CI 0.14-0.53), all-cause death (RR, 0.57; 95% CI 0.50-0.64), major bleeding (RR, 0.60; 95% CI 0.51-0.72) and intracranial or gastrointestinal bleeding (RR, 0.61; 95% CI, 0.51-0.73). In subgroup analysis, all NOACs showed similar rates of stroke or systemic embolism, ischaemic stroke but reduced rates of all-cause death, major bleeding and intracranial or gastrointestinal bleeding compared to VKAs. ConclusionsIn this combined analysis of real-world observational studies, NOACs showed lower risks of stroke or systemic embolism, ischaemic stroke, VTE, all-cause death and reduced rates of major bleeding and intracranial or gastrointestinal bleeding compared to VKAs in patients with AF and cancer.

scholarly journals Reappraisal of Non-vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Fuwei Liu ◽  
Yunyao Yang ◽  
Winglam Cheng ◽  
Jianyong Ma ◽  
Wengen Zhu
Keyword(s):  
Atrial Fibrillation ◽  
Systematic Review ◽  
Propensity Score ◽  
Vitamin K ◽  
Major Bleeding ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism

Background: Recent observational studies have compared effectiveness and safety profiles between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with atrial fibrillation (AF). Nevertheless, the confounders may exist due to the nature of clinical practice-based data, thus potentially influencing the reliability of results. This systematic review and meta-analysis were conducted to compare the effect of NOACs with warfarin based on the propensity score-based observational studies vs. randomized clinical trials (RCTs).Methods: Articles included were systematically searched from the PubMed and EMBASE databases until March 2021 to obtain relevant studies. The primary outcomes were stroke or systemic embolism (SSE) and major bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the outcomes were extracted and then pooled by the random-effects model.Results: A total of 20 propensity score-based observational studies and 4 RCTs were included. Compared with warfarin, dabigatran (HR, 0.82 [95% CI, 0.71–0.96]), rivaroxaban (HR, 0.80 [95% CI, 0.75–0.85]), apixaban (HR, 0.75 [95% CI, 0.65–0.86]), and edoxaban (HR, 0.71 [95% CI, 0.60–0.83]) were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran (HR, 0.76 [95% CI, 0.65–0.87]), apixaban (HR, 0.61 [95% CI, 0.56–0.67]), and edoxaban (HR, 0.58 [95% CI, 0.45–0.74]) but not rivaroxaban (HR, 0.92 [95% CI, 0.84–1.00]) were significantly associated with a decreased risk of major bleeding based on the observational studies. Furthermore, the risk of major bleeding with dabigatran 150 mg was significantly lower in observational studies than that in the RE-LY trial, whereas the pooled results of observational studies were similar to the data from the corresponding RCTs in other comparisons.Conclusion: Data from propensity score-based observational studies and NOAC trials consistently suggest that the use of four individual NOACs is non-inferior to warfarin for stroke prevention in AF patients.

scholarly journals Comparative Effectiveness and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients

Stroke ◽  
2021 ◽  
Author(s):  
Wengen Zhu ◽  
Zi Ye ◽  
Shilan Chen ◽  
Dexi Wu ◽  
Jiangui He ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Inverse Variance

Background and Purpose: Several observational studies have compared the effect of the non–vitamin K antagonist oral anticoagulants to each other in patients with atrial fibrillation. However, confounding by indication is a major problem when comparing non–vitamin K antagonist oral anticoagulant treatments in some of these studies. This meta-analysis was conducted to compare the effectiveness and safety between non–vitamin K antagonist oral anticoagulant and non–vitamin K antagonist oral anticoagulant by only including the propensity score matching studies. Methods: We systematically searched the PubMed and Ovid databases until May 2020 to identify relevant observational studies. Hazard ratios (HRs) and 95% CIs of the reported outcomes were collected and then pooled by a random-effects model complemented with an inverse variance heterogeneity or quality effects model. Results: A total of 17 retrospective cohort studies were included in this meta-analysis. Compared with dabigatran use, the use of rivaroxaban was significantly associated with increased risks of stroke or systemic embolism (HR, 1.16 [95% CI, 1.05–1.29]) and major bleeding (HR, 1.32 [95% CI, 1.24–1.41]), whereas the use of apixaban was associated with a reduced risk of major bleeding (HR, 0.78 [95% CI, 0.67–0.90]) but not stroke or systemic embolism (HR, 0.84 [95% CI, 0.56–1.28]). Compared with rivaroxaban use, the use of apixaban was associated with a decreased risk of major bleeding (HR, 0.63 [95% CI, 0.54–0.73]) but not stroke or systemic embolism (HR, 0.83 [95% CI, 0.67–1.04]). Reanalyses with the inverse variance heterogeneity or quality effects model produced similar results as the random-effects model. Conclusions: Current observational comparisons with propensity score matching methods suggest that apixaban might be a better choice compared with dabigatran or rivaroxaban for stroke prevention in atrial fibrillation patients.

Abstract TP394: Comparison of Major Bleeding Endpoints Between Non-vitamin K Antagonist Oral Anticoagulants and Aspirin: A Network Meta-Analysis

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Wen-yi Huang ◽  
Daniel E Singer ◽  
Yi-Ling Wu ◽  
Hsu-Huei Weng ◽  
Meng Lee ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist
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