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Aldo Lorenzetti M.D, Internal Medicine & Hepatology, Milano - SIMEDET Delegate
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Non–Vitamin K Antagonist Oral #Anticoagulants in Patients With Atrial Fibrillation and #Valvular Heart Disease
http://www.onlinejacc.org/content/69/11/1363

We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.

Conclusions
High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.
Association Between Use of Non–Vitamin K Oral #Anticoagulants With and Without Concurrent Medications and Risk of Major #Bleeding in Nonvalvular Atrial #Fibrillation

http://jamanetwork.com/journals/jama/article-abstract/2656168

Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk

Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 99% CI, 9.76-18.13); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 99% CI, 80.96-195.97); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone.

Conclusions and Relevance Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs
Comparative safety of direct oral #anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study
http://www.bmj.com/content/359/bmj.j4323

To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous #thromboembolism Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.

Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.
Oral #anticoagulants for prevention of stroke in atrial #fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis
http://www.bmj.com/content/359/bmj.j5058

.. 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.

Conclusions The 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.
2017 ACC Expert Consensus Decision Pathway on Management of #Bleeding in Patients on Oral #Anticoagulants
A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways
http://www.onlinejacc.org/content/early/2017/11/10/j.jacc.2017.09.1085

.. Expert Consensus Documents are intended to provide guidance for clinicians in areas in which evidence may be limited or new and evolving, or in which data are insufficient to fully inform clinical decision making.

In an effort to increase the impact of ACC policy on patient care, an ACC Presidential Task Force was formed in 2014 to examine the ACC’s clinical documents. The main recommendation of the Task Force was a new focus on concise decision pathways and/or key points of care, instead of the traditional longer documents. The Task Force also established criteria for identifying high-value clinical topics to be addressed, as well as an innovative approach to collecting stakeholder input through a roundtable or think tank meeting. To complement the new focus on brief decision pathways and key points, Expert Consensus Documents were rebranded “Expert Consensus Decision Pathways” (ECDPs)
Direct Oral #Anticoagulants in Addition to Antiplatelet Therapy for Secondary Prevention After Acute #Coronary Syndromes

A Systematic Review and Meta-analysis

https://jamanetwork.com/journals/jamacardiology/article-abstract/2672050?redirect=true


Six trials that included 29 667 patients were identified (14 580 patients 49.1% with STEMI and 15 036 50.7% with NSTE-ACS). The primary efficacy end point risk was significantly lower in patients who were treated with DOAC as compared with APT alone (odds ratio OR, 0.85; 95% CI, 0.77-0.93; P < .001). This benefit was pronounced in patients with STEMI (OR, 0.76; 95% CI, 0.66-0.88; P < .001), while no significant treatment effect was observed in patients with NSTE-ACS (OR, 0.92; 95% CI, 0.78-1.09; P = .36; P for interaction = .09). With respect to safety, DOACs were associated with a higher risk of major bleeding as compared with APT alone (OR, 3.17; 95% CI, 2.27-4.42; P < .001), with consistent results in patients with STEMI (OR, 3.45; 95% CI, 1.95-6.09; P < .001) and NSTE-ACS (OR, 2.19; 95% CI, 1.38-3.48; P < .001; P for interaction = .23).


Conclusions and Relevance To our knowledge, these findings are the first evidence to support differential treatment effects of DOAC in addition to APT according to ACS baseline clinical presentation. In patients with NSTE-ACS, the risk-benefit profile of DOAC appears unfavorable. Conversely, DOAC in addition to APT might represent an attractive option for patients with STEMI
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Risks and benefits of direct oral #anticoagulants versus #warfarin in a real world setting: cohort study in primary care

https://www.bmj.com/content/362/bmj.k2505


In patients with atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (adjusted hazard ratio 0.66, 95% confidence interval 0.54 to 0.79) and intracranial bleeding (0.40, 0.25 to 0.64); dabigatran was associated with a decreased risk of intracranial bleeding (0.45, 0.26 to 0.77). An increased risk of all cause mortality was observed in patients taking rivaroxaban (1.19, 1.09 to 1.29) or on lower doses of apixaban (1.27, 1.12 to 1.45). In patients without atrial fibrillation, compared with warfarin, apixaban was associated with a decreased risk of major bleeding (0.60, 0.46 to 0.79), any gastrointestinal bleeding (0.55, 0.37 to 0.83), and upper gastrointestinal bleeding (0.55, 0.36 to 0.83); rivaroxaban was associated with a decreased risk of intracranial bleeding (0.54, 0.35 to 0.82). Increased risk of all cause mortality was observed in patients taking rivaroxaban (1.51, 1.38 to 1.66) and those on lower doses of apixaban (1.34, 1.13 to 1.58).

Conclusions Overall, apixaban was found to be the safest drug, with reduced risks of major, intracranial, and gastrointestinal bleeding compared with warfarin. Rivaroxaban and low dose apixaban were, however, associated with increased risks of all cause mortality compared with warfarin
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Effect of #anticoagulants and #NSAIDs on accuracy of faecal immunochemical tests (#FITs) in colorectal cancer screening: a systematic review and meta-analysis

https://gut.bmj.com/content/early/2018/06/05/gutjnl-2018-316344


Our literature search identified 2022 records, of which 8 studies were included. A total of 3563 participants with a positive FIT were included. Use of OACs was associated with a PPVAN of 37.6% (95% CI 33.9 to 41.4) compared with 40.3% (95% CI 38.5 to 42.1) for non-users (p=0.75). Pooled PPVAN in aspirin/NSAID users was 38.2% (95% CI 33.8 to 42.9) compared with 39.4% (95% CI 37.5 to 41.3) for non-users (p=0.59).

Conclusion FIT accuracy is not affected by OACs and aspirin/NSAIDs use. Based on the current literature, withdrawal of OACs or NSAIDs before FIT screening is not recommended. Future studies should focus on duration of use, dosage and classes of drugs in association with accuracy of FIT to conduct more specific guideline recommendations.
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Assessment of Outcomes of Treatment With Oral #Anticoagulants in Patients With Atrial #Fibrillation and Multiple Chronic Conditions

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2703948

The study cohort included 21 979 patients using dabigatran (mean [SD] age, 75.8 [6.4] years; 51.1% female), 23 177 using rivaroxaban (mean [SD] age, 75.8 [6.4] years; 49.9% female), and 101 715 using warfarin (mean [SD] age, 78.5 [7.2] years; 57.3% female). In the propensity-matched cohorts, there were no differences in stroke rates between the 3 oral anticoagulant groups. Dabigatran users had lower hazard of MH compared with warfarin users among patients with low MCC (hazard ratio [HR], 0.62; 95% CI, 0.47-0.83; P < .001; for MCC defined as low CHA2DS2-VASc score), and similar risk in patients with moderate to high MCC. While there was no difference in MH between rivaroxaban and warfarin users, rivaroxaban users had significantly higher MH risk compared with dabigatran users in the medium and high comorbidity groups (HR, 1.24; 95% CI, 1.04-1.48; P = .02 and HR, 1.28; 95% CI, 1.05-1.56; P = .01, respectively). Dabigatran and rivaroxaban users had lower rates of death compared with warfarin users (HR ranged from 0.52-0.84), across comorbidity levels.

Conclusions and Relevance Oral anticoagulants are similarly effective in stroke prevention among patients with AF with MCC. However, dabigatran and rivaroxaban use may be associated with lower rates of mortality in patients with MCC
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Association of Oral #Anticoagulants and #Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding

https://jamanetwork.com/journals/jama/fullarticle/2717474

Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment

... When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, −24 [95% CI, −38 to −11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, −61.1 [95% CI, −74.8 to −47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, −35.5 [95% CI, −48.6 to −22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, −39.3 [95% CI, −44.5 to −34.2]).

Conclusions and Relevance Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents
Direct Oral #Anticoagulants in Atrial Fibrillation Patients with Concomitant #Hyperthyroidism

Patients with hyperthyroidism were excluded from randomized clinical trials of direct oral anticoagulants(DOACs) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF)..

After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio (HR):0.65; [95% confidential interval (CI):0.44-0.96]; P=0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, patients taking warfarin with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR:0.61; [95%CI:0.43-0.86]; P=0.0050).

Conclusion

Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study

https://bit.ly/2vbu19n
Effectiveness and Safety of Direct Oral #Anticoagulants Versus Warfarin in Patients With Valvular Atrial #Fibrillation
https://2medical.news/2021/03/31/effectiveness-and-safety-of-direct-oral-anticoagulants-versus-warfarin-in-patients-with-valvular-atrial-fibrillation/

Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited. Objective: To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF. Design: New-user retrospective propensity score–matched cohort study. Setting: U.S.-based commercial health care database from 1 January 2010 to 30 June 2019. …