Dataset Information

Efficacy and Safety of Non-recommended Dose of New Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

ABSTRACT: Introduction: The real-world treatment of atrial fibrillation (AF) often involves the prescription of new oral anticoagulants (NOACs) using dosing both lower and higher than recommended guidelines. Our study aimed to evaluate the efficacy and safety of non-recommended dosage of NOACs in AF patients. Methods: A systematic search was performed for relevant studies across multiple electronic databases (PubMed, Embase, Cochrane Library, Clinical Trials Registry) from inception to May 1, 2021. Multicenter randomized trials and observational studies were selected with key reporting measures for inclusion involved efficacy outcomes including stroke or systemic thromboembolism along with safety endpoints assessing major or clinically relevant bleeding events. Results: A total of 11 eligible studies were included involving 48,648 patients receiving recommended dose of NOACs and 50,116 patients receiving non-recommended dosage. Compared to AF patients treated with recommended dose regimens, administration of low dose of NOACs was associated with higher risk of stroke/systemic embolism (RR = 1.24, 95% CI 1.14-1.35, P < 0.00001), but without reducing bleeding risk (RR = 1.18, 95% CI 0.91-1.53, P = 0.21) and a higher risk of all-cause mortality (RR = 1.58, 95% CI 1.25-1.99, P = 0.0001). Moreover, high dose of NOACs was associated with higher risk of stroke and systemic embolism efficacy (RR = 1.71, 95% CI 1.06-2.76, P = 0.03) and a non-significant trend to a greater risk of major or clinically relevant bleeding (RR = 1.57, 95% CI 0.96-2.58, P = 0.07). Conclusions: AF patients treated with low dose of NOACs showed equivalent safety but with worse efficacy compared with recommended dose. High dose of NOACs was not superior to recommended dose regimens in preventing stroke/systemic embolism outcomes in AF patients.

SUBMITTER: Kong X

PROVIDER: S-EPMC8733406 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons.We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score ?3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban.An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score ?3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.

Project description:IntroductionNovel oral anticoagulants (NOACs) have been approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). A large number of patients are on NOACs when they present for AF ablation. We intended to evaluate the safety and efficacy of NOACs for AF ablation during the periprocedural period by performing a meta-analysis of trials comparing NOACs with warfarin.MethodsStudies comparing NOACs (dabigatran and rivaroxaban) with warfarin as periprocedural anticoagulants for AF ablation were identified using an electronic search. Primary outcomes were: (1) a composite endpoint of stroke, transient ischemic attack (TIA), peripheral arterial embolism, or silent cerebral lesions on magnetic resonance imaging (MRI) and (2) major bleeding complications. A random effects model was used to pool the safety and efficacy data across all included trials.ResultsWhen compared to warfarin, there was an increased risk of the composite endpoint of stroke, TIA, peripheral arterial embolism, or silent cerebral lesions on MRI with NOACs as periprocedural anticoagulants for AF ablation [odds ratio (OR): 1.69, 95% confidence interval (CI): 1.06-2.68]. Sub-group analysis revealed a higher risk of composite endpoint with dabigatran as a periprocedural anticoagulant for AF ablation (OR: 2.01, 95% CI: 1.19-3.39) whereas the risk was similar with rivaroxaban (OR: 0.90, 95% CI: 0.34-2.41). Sensitivity analysis after excluding silent cerebral lesions on MRI showed there was no increased risk of thromboembolic events with either dabigatran (OR: 1.69, 95% CI: 0.81-3.51) or rivaroxaban (OR: 0.70, 95% CI: 0.12-4.04). Risk of bleeding with NOACs was similar to warfarin (OR: 0.91, 95% CI: 0.62-1.34).ConclusionNOACs are comparable to warfarin in terms of bleeding complications. However, dabigatran therapy is potentially associated with a higher risk of silent cerebral lesions on MRI. The results of this study should be considered as hypothesis-generating and assessed further in prospective randomized clinical studies.

Project description:Background: Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk-benefit profile. However, there are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients. Methods: After comprehensively searching Embase, PubMed, and Cochrane databases, five phase III randomized controlled trials involving 28,137 elderly participants were included in this study. The efficacy outcome was stroke or systemic embolism, and the safety outcome was major bleeding. We conducted a network meta-analysis by using a Bayesian random-effect model for the first time to evaluate the efficacy and safety of main DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran) and warfarin in elderly patients with AF. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were used to assess the effect of drugs on efficacy and safety. The rank probabilities were used to reflect the hierarchy of drugs, and a larger rank probability value symbolized a better rank of drugs. Results: In the prophylaxis of stroke or systemic embolism, apixaban was found to be the best among DOACs compared to warfarin (HR, 0.71; 95% CI: 0.33-1.50), though this finding was not statistically significant. Apixaban ranked the best (rank probabilities, 41.2%) in efficacy of drugs, followed by rivaroxaban, edoxaban, dabigatran, and warfarin (rank probabilities, 31.8, 15.9, 10.9, and 0.2%, respectively). In reducing the risk of major bleeding, apixaban was found to be the best among DOACs too, compared to warfarin (HR, 0.64; 95% CI: 0.33-1.30), though this finding was not statistically significant. In safety, apixaban ranked the best (rank probabilities, 71.4%), followed by edoxaban, dabigatran, warfarin, and rivaroxaban (rank probabilities, 21.0, 5.8, 0.9, and 0.8%, respectively). Conclusions: DOACs showed a lower incidence of stroke/systemic embolism and major bleeding compared with warfarin in antithrombotic therapy in elderly patients (aged ≥75 years), with apixaban being the best of those interventions. Therefore, apixaban should be given priority as an anticoagulant in stroke prevention for elderly patients with AF.

Project description:Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and safety. Methods: Using administrative data from Quebec province, Canada, we built a cohort of new warfarin or DOAC users discharged from hospital between 2011 and 2017. We determined CHA2DS2-VASc and HAS-BLED scores, and comorbidities for 3-year prior cohort entry. The primary effectiveness endpoint was a composite of ischemic stroke/systemic embolism (SE), and secondary outcomes included a safety composite of major bleeding (MB) events and effectiveness composite (stroke/SE, death) at 1-year follow-up. We contrasted each low-dose DOAC with warfarin or other DOACs as references using inverse probability of treatment weighting to estimate marginal Cox hazard ratios (HRs). Results: The cohort comprised 22,969 patients (mean age: 80-86). We did not find a significant risk reduction for the stroke/SE primary effectiveness endpoint for DOACs vs. warfarin; however, we observed a significantly lower risk for low-dose dabigatran vs. warfarin (HR [95%CI]: 0.59 [0.42-0.81]) for effectiveness composite, mainly due to a lower death rate. The differences in effectiveness and safety composites between low-dose rivaroxaban vs. warfarin were not significant. However, low-dose apixaban had a better safety composite (HR: 0.68 [0.53-0.88]) vs. warfarin. Comparisons of dabigatran vs. apixaban showed a lower risk of stroke/SE (HR: 0.53 [0.30-0.93]) and a 2-fold higher risk of MB. The MB risk was higher for rivaroxaban than for apixaban (HR: 1.58 [1.09-2.29]). Conclusions: The results of this population-based study suggest that low-dose dabigatran has a better effective composite than warfarin. Compared with apixaban, low-dose dabigatran had a better effectiveness composite but a worse safety profile. Low-dose apixaban had a better safety composite than warfarin and other low-dose DOACs. Given that the comparative effectiveness and safety seem to vary from one DOAC to another, pharmacokinetic data for specific populations are now warranted.

Dataset Information

Efficacy and Safety of Non-recommended Dose of New Oral Anticoagulants in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets