Meta-Analysis of Direct-Acting Oral Anticoagulants Compared With Warfarin in Patients >75 Years of Age

2019 ◽  
Vol 123 (12) ◽  
pp. 2051-2057 ◽  
Author(s):  
Aaqib H. Malik ◽  
Srikanth Yandrapalli ◽  
Wilbert S. Aronow ◽  
Julio A. Panza ◽  
Howard A. Cooper
2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Shetty ◽  
H Malik

Abstract Background Direct-acting oral anticoagulants (DOACs) are now the preferred choice over warfarin in patients with atrial fibrillation (AF). The comparative efficacy and safety of DOACs over warfarin in patients with and without diabetes mellitus (DM) has not been fully evaluated. Purpose To evaluate the efficacy and safety of DOACs compared to warfarin in patients with non-valvular atrial fibrillation with and without DM. Methods A comprehensive review of the literature was performed to identify RCTs with data on DOACs compared to warfarin in the subgroups of DM and nonN-DM. Our outcome of interest were stroke/systemic embolization (SSE) and major bleeding. A random-effects meta-analysis was performed. We further performed a network meta-analysis to assess the most effective of all the therapies for the above mentioned subgroups. Results Our search identified 4 RCTs with 71,683 randomized patients, of which 22,087 were DM and 49,596 were non-DM. The mean duration of follow up was 2.3 years. Our results showed that the DOACS were associated with lower odds for SSE in diabetics (OR 0.80; 95% CI 0.67–0.95; p-value=0.01) and non-diabetics (OR 0.81; 95% CI 0.71–0.92; p-value<0.01). For major bleeding, DOACs were non-inferior to warfarin in DM (OR 0.94; 95% CI 0.80–1.09; p-value=0.42) and non-DM (OR 0.82; 95% CI 0.62–1.07; p-value=0.15). (Fig 1) Network meta-analysis showed that dabigatran was the most effective for the outcome of SSE irrespective of DM status. However, edoxaban and apixaban were the safest of the DOACs for the outcome of major bleeding (Table 1) Conclusion In this meta-analysis of RCT, we found that DOACs are more effective and similarly safe compared to warfarin irrespective of the diabetic status of the patient. Funding Acknowledgement Type of funding source: None


2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 182S-187S ◽  
Author(s):  
Diana M. Sobieraj ◽  
William L. Baker ◽  
Eni Smith ◽  
Katarzyna Sasiela ◽  
Stephanie E. Trexler ◽  
...  

To perform a systematic review and network meta-analysis evaluating the efficacy and safety of low-molecular-weight heparins (LMWHs), vitamin K antagonists (VKAs), and direct-acting oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). We searched MEDLINE, Cochrane Central Register of Controlled Trials, and conference abstracts through March 2018. Randomized controlled trials (RCTs) enrolling adults with CAT comparing 2 or more full-dose anticoagulants (LMWH, VKA, and DOAC) and evaluating recurrent venous thromboembolism (VTE), major bleeding, and/or all-cause mortality were included. Reviewers identified studies, extracted data, and assessed the quality of the evidence in duplicate. A frequentist network meta-analysis, which uses direct and indirect evidence to simultaneously compare multiple interventions, was performed using a random-effects approach. Results are reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). We included 13 RCTs (n = 6292): 7 compared LMWHs with VKAs, 4 compared DOACs with VKAs, and 2 compared DOACs with LMWHs. The risk of recurrent VTE was significantly reduced by 28% and 54% with a DOAC compared to an LMWH and a VKA, respectively. Low-molecular-weight heparins significantly reduced the risk of recurrent VTE by 36% versus VKAs. The risk of major bleeding was 14% higher with DOACs compared to LMWHs and 15% and 25% lower with DOACs and LMWHs versus VKAs, although 95% CIs included unity for each. The risk of all-cause mortality appeared similar for all 3 comparisons (RR = 1.0 for each comparison). Direct-acting oral anticoagulants appeared superior in reducing recurrent VTE in patients with CAT compared to LMWH and VKAs, but an increased risk of major bleeding versus LMWH cannot be ruled out.


Author(s):  
Abdulrhman Al Rowily ◽  
Zahraa Jalal ◽  
Malcolm J. Price ◽  
Mohammed H. Abutaleb ◽  
Hind Almodiaemgh ◽  
...  

Abstract Purpose This study aimed to estimate the prevalence, contributory factors, and severity of medication errors associated with direct acting oral anticoagulants (DOACs). Methods A systematic review and meta-analysis were undertaken by searching 11 databases including Medline, Embase, and CINHAL between January 2008 and September 2020. The pooled prevalence of errors and predictive intervals were estimated using random-effects models using Stata software. Data related to error causation were synthesised according to Reason’s accident causation model. Results From the 5205 titles screened, 32 studies were included which were mostly based in hospitals and included DOAC treatment for thromboembolism and atrial fibrillation. The proportion of study population who experienced either prescription, administration, or dispensing error ranged from 5.3 to 37.3%. The pooled percentage of patients experiencing prescribing error was 20% (95% CI 15–25%; I2 = 96%; 95% PrI 4–43%). Prescribing error constituted the majority of all error types with a pooled estimate of 78% (95%CI 73–82%; I2 = 0) of all errors. The common reported causes were active failures including wrong drug, and dose for the indication. Mistakes such as non-consideration of renal function, and error-provoking conditions such as lack of knowledge were common contributing factors. Adverse events such as potentially fatal intracranial haemorrhage or patient deaths were linked to the errors but causality assessments were often missing. Conclusions Despite their favourable safety profile, DOAC medication errors are common. There is a need to promote multidisciplinary working, guideline-adherence, training, and education of healthcare professionals, and the use of theory-based and technology-facilitated interventions to minimise errors and maximise the benefits of DOACs usage in all settings. Protocol A protocol developed as per PRISMA-P guideline is registered under PROSPERO ID = CRD42019122996


VASA ◽  
2019 ◽  
Vol 48 (2) ◽  
pp. 134-147 ◽  
Author(s):  
Mirko Hirschl ◽  
Michael Kundi

Abstract. Background: In randomized controlled trials (RCTs) direct acting oral anticoagulants (DOACs) showed a superior risk-benefit profile in comparison to vitamin K antagonists (VKAs) for patients with nonvalvular atrial fibrillation. Patients enrolled in such studies do not necessarily reflect the whole target population treated in real-world practice. Materials and methods: By a systematic literature search, 88 studies including 3,351,628 patients providing over 2.9 million patient-years of follow-up were identified. Hazard ratios and event-rates for the main efficacy and safety outcomes were extracted and the results for DOACs and VKAs combined by network meta-analysis. In addition, meta-regression was performed to identify factors responsible for heterogeneity across studies. Results: For stroke and systemic embolism as well as for major bleeding and intracranial bleeding real-world studies gave virtually the same result as RCTs with higher efficacy and lower major bleeding risk (for dabigatran and apixaban) and lower risk of intracranial bleeding (all DOACs) compared to VKAs. Results for gastrointestinal bleeding were consistently better for DOACs and hazard ratios of myocardial infarction were significantly lower in real-world for dabigatran and apixaban compared to RCTs. By a ranking analysis we found that apixaban is the safest anticoagulant drug, while rivaroxaban closely followed by dabigatran are the most efficacious. Risk of bias and heterogeneity was assessed and had little impact on the overall results. Analysis of effect modification could guide the clinical decision as no single DOAC was superior/inferior to the others under all conditions. Conclusions: DOACs were at least as efficacious as VKAs. In terms of safety endpoints, DOACs performed better under real-world conditions than in RCTs. The current real-world data showed that differences in efficacy and safety, despite generally low event rates, exist between DOACs. Knowledge about these differences in performance can contribute to a more personalized medicine.


2019 ◽  
Vol 24 (38) ◽  
pp. 4534-4539 ◽  
Author(s):  
Eric Zimmermann ◽  
Fawzi Ameer ◽  
Berhane Worku ◽  
Dimitrios Avgerinos

Introduction: Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. Literature Search: We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). Case Presentation: We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Conclusion: Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.


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