Safety and Efficacy of Apixaban versus warfarin in patients with atrial fibrillation or Venous Thromboembolism and End-Stage renal disease on hemodialysis: A systematic review and meta-analysis.

BACKGROUND: Warfarin is traditionally the drug of choice for stroke prophylaxis or treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) on hemodialysis as data on apixaban use is scarce. We aimed to assess the safety and efficacy of Apixaban in patients with ESRD on hemodialysis when compared with warfarin. METHODS: A comprehensive literature search in PubMed, Google Scholar, and Cochrane databases from inception until Nov 25, 2019, was performed. Studies reporting clinical outcomes comparing Apixaban (2.5 mg BID or 5 mg BID) versus Warfarin in ESRD patients on hemodialysis were included. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data. RESULTS: Four studies (three retrospective and one randomized) with a total of 9862 patients (apixaban = 2,547, warfarin = 7315) met inclusion criteria. The overall mean age was 66.6 ± 3.9 years and mean CHA2DS2-VASc score 4.56 ± 0.58. Apixaban was associated with lower rates of major bleeding (RR 0.53, 95% CI 0.45-0.64, p < 0.0001], gastrointestinal (GI) bleed (RR 0.65, 95% CI 0.55-0.76, p < 0.0001), intracranial bleed (RR 0.56, 95% CI 0.36-0.89, p = 0.01), and stroke/systemic embolism [RR 0.65, 95% CI 0.52-0.83, p = 0.0004] compared with warfarin in patients with ESRD on hemodialysis. There was no significant increased risk of all-cause mortality with the apixaban vs. warfarin (RR 0.90, 95% CI 0.41-1.96, p = 0.78). CONCLUSION: Apixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to Warfarin in ESRD patients on hemodialysis with non-valvular AF and/or venous thromboembolism.

Risks and Benefits of Removal of the Left Atrial Appendage.

PURPOSE OF REVIEW: In patients with atrial fibrillation who are unable to take novel oral anticoagulants for stroke prophylaxis due to bleeding risk or other contraindications, left atrial appendage (LAA) occlusion and exclusion devices have shown benefit. In this review, we highlight the risks and benefits associated with LAA removal. RECENT FINDINGS: LAA, once considered a vestigial organ, has been shown to have physiological, anatomical, and arrhythmogenic properties. Device-related complications such as pericardial effusion, device embolization, device-related thrombus, while uncommon, are still present. With increased operator experience related to appendage occlusion, overall procedural complications have declined. Further refinements in device technology will help decrease complications. While benefits of appendage removal are plenty, procedural complications need to be weighed into the equation when making decisions regarding LAA occlusion.

Warfarin vs non-vitamin K oral anticoagulants for left atrial appendage thrombus: A meta-analysis.

INTRODUCTION: Novel oral anticoagulants (NOACs) are commonly used for thromboembolic risk reduction and treatment of pulmonary embolism and deep venous thrombosis. However, data regarding their efficacy and safety in comparison to warfarin for left atrial appendage thrombus is limited. METHODS: A comprehensive literature search in PubMed, Google Scholar, and Cochrane Review from inception to 30 October 2019 was performed. Studies reporting clinical outcomes comparing warfarin vs NOACs were included. Two investigators independently extracted the data and individual quality assessment was performed. A meta-analysis was performed using random-effects model to calculate risk ratio (RR) and 95% confidence interval (CI). The analysis was performed using RevMan 5.3. RESULTS: Four studies met inclusion criteria and a total of 322 patients were included of whom 141 were in the NOAC arm and 181 were in the warfarin arm. There was no significant difference in thrombus resolution between the two groups (RR, 1.00; 95% CI [0.77-1.29; P = .98]). There was no significant difference in major bleeding (RR, 1.30; 95% CI [0.14-12.21; P = .82]) or stroke (RR, 0.42; 95% CI [0.09-2.06; P = .29]) between the two groups. CONCLUSION: The results of our meta-analysis show that NOACs are as efficacious and safe as warfarin in the treatment of left atrial appendage thrombus in patients with non-valvular atrial fibrillation.

Correlation of Somatic Genomic Alterations Between Tissue Genomics and ctDNA Employing Next-Generation Sequencing: Analysis of Lung and Gastrointestinal Cancers.

Next-generation Sequencing (NGS) of cancer tissues is increasingly being carried out to identify somatic genomic alterations that may guide physicians to make therapeutic decisions. However, a single tissue biopsy may not reflect complete genomic architecture due to the heterogeneous nature of tumors. Circulating tumor DNA (ctDNA) analysis is a robust noninvasive method to detect and monitor genomic alterations in blood in real time. We analyzed 28 matched tissue NGS and ctDNA from gastrointestinal and lung cancers for concordance of somatic genomic alterations, driver, and actionable alterations. Six patients (21%) had at least one concordant mutation between tissue and ctDNA sequencing. At the gene level, among all the mutations (n = 104) detected by tissue and blood sequencing, 7.7% (n = 8) of mutations were concordant. Tissue and ctDNA sequencing identified driver mutations in 60% and 64% of the tested samples, respectively. We found high discordance between tissue and ctDNA testing, especially with respect to the driver and actionable alterations. Both tissue and ctDNA NGS detected actionable alterations in 25% of patients. When somatic alterations identified by each test were combined, the total number of patients with actionable mutations increased to 32%. Our data show significant discordance between tissue NGS and ctDNA analysis. These results suggest tissue NGS and ctDNA NGS are complementary approaches rather than exclusive of each other. When performed in isolation, tissue and ctDNA NGS can each potentially miss driver and targetable alterations, suggesting that both approaches should be incorporated to enhance mutation detection rates. Larger prospective studies are needed to better clarify this emerging precision oncology landscape. Mol Cancer Ther; 17(5); 1123-32. ©2018 AACR.