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[This corrects the article DOI: 10.1371/journal.pone.0232354.].

INTRODUCTION:Oral anticoagulants play an integral role in the prevention and treatment of cerebral and systemic thromboembolism. Traditionally, this has been managed with vitamin K antagonists, primarily warfarin. Over time, however, the use of direct oral anticoagulants (DOACs) have gained popularity. Unsurprisingly, the initiation of a medication that decreases the blood's ability to clot increases the risk of bleeding. The aim of this study was to examine the incidence of gastrointestinal bleeding (GIB) in patients enrolled in an anticoagulation clinic at a Veterans Affairs (VA) medical center.METHODS:The VA's Computerized Patient Record System was used to create a list of patients seen in the VA anticoagulation (AC) clinic from 10/2010 to 9/2016. A sample of 1997 patients was randomly selected using a web-based program. Based on the formulary at the VA, only warfarin, rivaroxaban, dabigatran, and apixaban were examined. Demographics, indications for anticoagulation, and relevant comorbidities and concomitant medications were recorded.RESULTS:Despite increasing use of DOACs since their introduction in 2011, results of the analysis indicate warfarin was still the most commonly prescribed anticoagulant in our population with 1270/1997 (64%). Rivaroxaban was taken by 28%, apixaban by 13%, and dabigatran by 10%. GIB was seen in 31/1270 patients (1.55%). In those taking warfarin, 28/1270 (2.3%) had GIB (P < 0.001). GIB was seen in 3/552 patients taking rivaroxaban (0.5%, P = 0.024). GIB was seen in 5/256 patients taking apixaban (2%), but this did not reach statistical significance. GIB was seen in 1/198 patients taking dabigatran (0.5%), but this did not reach statistical significance. Factors associated with increased risk of GI bleeding included chronic kidney disease and diabetes mellitus. Patients not on proton pump inhibitors, clopidogrel, and nonsteroidal anti-inflammatory medications had an increased risk of GIB.CONCLUSION:Given similar efficacy of DOACs to warfarin shown in prior studies, the choice of oral anticoagulant rests largely on the safety profile. In a population of patients seen in the VA AC clinic, the most commonly prescribed anticoagulant was warfarin. The risk of GI bleeding was highest in these patients, similar to findings in previous studies. The lowest risk was seen with dabigatran. A data set with more GIB patients would allow multiple logistic regression analysis of the medications and comorbidities identified as risk factors.

In a large trial, the estimated incidence of stroke, systemic embolism, hemorrhage, or death was 2.8 percentage points lower to 0.5 percentage points higher with early than with later use of direct oral anticoagulants.

Corresponding author's email: hiroya45hayashi@ncvc.go.jp Background: The use of direct oral anticoagulant (DOAC) may provide the stable effect and safety in the early phase of PTE therapy. [...]we evaluated right ventricle / left ventricle (RV/LV) ratio on computed tomography and BNP at admission and discharge.

The availability of direct oral anticoagulants has caused a paradigm shift in themanagement of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whosetarget specificity is activated factor X (FXa). However, it is still not fully understoodif and how xabans impact platelet function. This observational study aimed to assess thein vitro platelet function in patients with atrial fibrillation receiving xabans. This wasa single-center study quantifying platelet aggregation in 41 patients treated withapixaban or rivaroxaban by light transmission aggregometry. The thrombin receptoractivating peptide (TRAP)-induced platelet aggregation was significantly lower 2 hoursafter taking rivaroxaban or apixaban compared to baseline value (56.15% [8.53%] vs 29.51%[12.9%]; P = .000). Moreover, concomitant use of angiotensin-convertingenzyme blockers, proton pump inhibitors, and statins reduces the efficiency of xabans. TheTRAP-induced platelet aggregation was reduced in patients with cardiovascular disease 2hours after receiving xabans.

Apixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism. The absolute oral bioavailability of apixaban is ~ 50%. Food does not have a clinically meaningful impact on the bioavailability. Apixaban exposure increases dose proportionally for oral doses up to 10 mg. Apixaban is rapidly absorbed, with maximum concentration occurring 3–4 h after oral administration, and has a half-life of approximately 12 h. Elimination occurs via multiple pathways including metabolism, biliary excretion, and direct intestinal excretion, with approximately 27% of total apixaban clearance occurring via renal excretion. The pharmacokinetics of apixaban are consistent across a broad range of patients, and apixaban has limited clinically relevant interactions with most commonly prescribed medications, allowing for fixed dosages without the need for therapeutic drug monitoring. The pharmacodynamic effect of apixaban is closely correlated with apixaban plasma concentration. This review provides a summary of the pharmacokinetic, pharmacodynamic, biopharmaceutical, and drug–drug interaction profiles of apixaban. Additionally, the population-pharmacokinetic analyses of apixaban in both healthy subjects and in the target patient populations are discussed.

AbstractObjectiveTo compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.DesignSystematic review, network meta-analysis, and cost effectiveness analysis.Data sourcesMedline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studiesPublished randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.ConclusionsThe network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registrationPROSPERO CRD 42013005324.

In a randomized trial, patients with severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care pharmacologic thromboprophylaxis. At 21 days, therapeutic-dose anticoagulation did not improve hospital survival or the number of days free of cardiovascular or respiratory organ support.

In a randomized trial, patients with moderately severe Covid-19 were assigned to receive either therapeutic-dose anticoagulation or usual-care thromboprophylaxis. At 21 days, therapeutic-dose anticoagulation resulted in a higher probability of survival until hospital discharge without organ support.