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Non-vitamin K Antagonist Oral Anticoagulants vs. Warfarin at Risk of Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Warfarin is a traditional oral anticoagulant for preventing thrombotic events in patients with atrial fibrillation (AF) and venous thromboembolism. Along with the widespread clinical use, the potential association between warfarin use and fracture risk have been addressed gradually. Non-vitamin K antagonist oral anticoagulants (NOACs), targeting thrombin or Xa factor, have been recommended as an optimal alternative due to their favorable property of thromboembolism prophylaxis and reduced bleeding risk. However, evidence of the fracture risk with NOACs use is limited. Therefore, the present study investigated this issue by a meta-analysis. Medline, Embase, Cochrane Library and the ClinicalTrials.gov Website were searched for randomized controlled trials (RCTs) that reported the fracture data of NOACs and warfarin. The primacy outcome was a composite of any fracture. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models according to between-study heterogeneity. Heterogeneity was assessed through I2 test and Q statistic, and the number of patients needed to treat (NNT) was calculated based on fracture incidence. Subgroup analyses were conducted according to individual NOACs, indications, and duration of follow up. Finally, 12 RCTs involving 89,549 patients were included, among which 44,816 (50%) receiving NOACs and 44,733 (50%) receiving warfarin. Overall, 1,139 (1.3%) patients including 515 NOACs users (1.1%) and 624 warfarin users (1.4%) developed fracture. Risk of fracture was significantly lower in NOACs compared to warfarin (RR: 0.82, 95%CI: 0.73-0.93, P = 0.001), with a NNT of 333. No significantly decreased risk was detected according to fracture sites. Subgroup analysis confirmed that the estimate of decreased fracture risk was derived mainly from AF patients receiving long-term anticoagulation treatment. The meta-regression did not detect any potential confounding on fracture risk. No heterogeneity between the studies (I2 = 15.0%) and no publication bias was identified. In conclusion, the use of NOACs was associated with a lower risk of fracture compared to warfarin, but with a relatively low absolute risk reduction. Therefore, screening for the fracture risk should be considered before initiating anticoagulation treatment. For patients who are at high risk of fracture or expected long-term treatment of anticoagulation, NOACs may represent a preferable alternative to warfarin.

SUBMITTER: Gu ZC

PROVIDER: S-EPMC5903161 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Non-vitamin K Antagonist Oral Anticoagulants vs. Warfarin at Risk of Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gu Zhi-Chun ZC Zhou Ling-Yun LY Shen Long L Zhang Chi C Pu Jun J Lin Hou-Wen HW Liu Xiao-Yan XY

Frontiers in pharmacology 20180410

Warfarin is a traditional oral anticoagulant for preventing thrombotic events in patients with atrial fibrillation (AF) and venous thromboembolism. Along with the widespread clinical use, the potential association between warfarin use and fracture risk have been addressed gradually. Non-vitamin K antagonist oral anticoagulants (NOACs), targeting thrombin or Xa factor, have been recommended as an optimal alternative due to their favorable property of thromboembolism prophylaxis and reduced bleedi ...[more]

PMID: 29692734

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Project description:Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141?311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141?311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15?036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39?585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.

Project description:BackgroundEmulating randomized controlled trials (RCTs) by real-world evidence (RWE) studies would benefit future clinical and regulatory decision-making by balancing the limitations of RCT. We aimed to evaluate whether the findings from RWE studies can support regulatory decisions derived from RCTs of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE).MethodsFive landmark trials (AMPLIFY, RE-COVER II, Hokusai-VTE, EINSTEIN-DVT, and EINSTEIN-PE) of NOACs were emulated using the South Korean nationwide claims database (January 2012 to August 2020). We applied an active comparator and new-user design to include patients who initiated oral anticoagulants within 28 days from their VTE diagnoses. The prespecified eligibility criteria, exposure (each NOAC, such as apixaban, rivaroxaban, dabigatran, and edoxaban), comparator (conventional therapy, defined as subcutaneous heparin followed by warfarin), and the definition of outcomes from RCTs were emulated as closely as possible in each separate emulation cohort. The primary outcome was identical to each trial, which was defined as recurrent VTE or VTE-related death. The safety outcome was major bleeding. Propensity score matching was conducted to balance 69 covariates between the exposure groups. Effect estimates for outcomes were estimated using the Mantel-Haenszel method and Cox proportional hazards model and subsequently compared with the corresponding RCT estimates.ResultsCompared to trial populations, real-world study populations were older (range: 63-69 years [RWE] vs. 54-59 years [RCT]), with more females (55-60.5% vs. 39-48.3%) and had a higher prevalence of active cancer (4.2-15.4% vs. 2.5-9.5%). The emulated estimates for effectiveness outcomes showed superior effectiveness of NOAC (AMPLIFY: relative risk 0.81, 95% confidence interval 0.70-0.94; RE-COVER II: hazard ratio [HR] 0.60, 0.37-0.96; Hokusai-VTE: 0.49, 0.31-0.78; EINSTEIN-DVT: 0.54, 0.33-0.89; EINSTEIN-PE: 0.50, 0.34-0.74), when contrasted with trials that showed non-inferiority. For safety outcomes, all emulations except for AMPLIFY and EINSTEIN-DVT yielded results consistent with their corresponding RCTs.ConclusionsThis study revealed the feasibility of complementing RCTs with RWE studies by using claims data in patients with VTE. Future studies to consider the different demographic characteristics between RCT and RWE populations are needed.

Project description:BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.Data sourcesStudies were searched for in PubMed and Google Scholar databases.Study eligibility criteriaStudies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.Study appraisal and synthesis methods25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR) with 95% confidence interval (CI). The random-effects or the fixed effect model were used to synthesize results from the selected studies.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.Conclusions and implicationsThe use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.

Dataset Information

Non-vitamin K Antagonist Oral Anticoagulants vs. Warfarin at Risk of Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Publications

Non-vitamin K Antagonist Oral Anticoagulants vs. Warfarin at Risk of Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Similar Datasets

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