Direct Oral Anticoagulants: From Randomized Clinical Trials to Real-World Clinical Practice

Roberti, Roberta; Iannone, Luigi Francesco; Palleria, Caterina; Curcio, Antonio; Rossi, Marco; Sciacqua, Angela; Armentaro, Giuseppe; Vero, Anna; Manti, Antonia; Cassano, Velia; Russo, Emilio; Sarro, Giovambattista De; Citraro, Rita

doi:10.3389/fphar.2021.684638

Cited by 48 publications

(31 citation statements)

References 105 publications

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“…Due to the prevalence to prothrombotic complications in many diseases, numerous studies devoted to substances with anticoagulant activity have been executed [ 42 , 43 ]. In contrast to advances in the antithrombotic therapy development, research on the modulation of fibrinolytic proteins is less advanced.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Hemostatic Activity of New Amide Derivatives

et al. 2022

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Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Hemostatic Activity of New Amide Derivatives

et al. 2022

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“…Even if age remains one of the strongest risk factors for stroke in patients with atrial fibrillation (AF), real-world data suggest that a significant proportion of older patients are still not receiving stroke prophylaxis treatment in line with guideline recommendations, even in the absence of contraindications to oral anticoagulants ( Steinberg et al, 2015 ). In addition to that, other important factors could influence the safety issue of the DOACs: the indication of use for which the DOAC is given, its dose, the concomitant drugs, linked to the potential risk of pharmacokinetic and pharmacodynamic drug-drug interaction, the comorbidities, and the duration of therapy ( Roberti et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Direct Oral Anticoagulants (DOACs) and Warfarin With Haemorrhagic Risk by Applying Correspondence Analysis to Data From the Italian Pharmacovigilance Database – A Case Study

et al. 2021

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Introduction: Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context.Objective: In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, Rete Nazionale di Farmacovigilanza), by comparing with disproportionality analysis on warfarin and DOACs.Methods: Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH).Results: We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH.Conclusion: Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.

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“…However, due to the observed gastrointestinal bleeding risk, NOACs use should be carefully evaluated in patients with gastric cancer. Before starting NOACs, potential drug-drug interactions (DDIs) and avoid their administration with chemotherapy drugs that strongly induce or inhibit P-glycoprotein (P-gp) or CYP3A4 pathways [31].…”

Section: Cancer and Vtementioning

confidence: 99%

Expert Recommendations on the Usage of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) from India: Current Perspective and Future Direction

Pai

Kumar²,

George

et al. 2022

Cardiol Ther

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Non-vitamin K antagonist oral anticoagulants (NOACs) are a new class of anticoagulant drugs used in the prevention and treatment of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulation requires the integration of the correct type and dose of oral anticoagulants based on patient characteristic, and therefore therapy needs to be individualized for each patient. Growing scientific evidence from studies on NOACs has led to a better understanding of their benefits and safety. A large amount of available data creates a necessity for an adaptable practical document for the usage of NOACs in India. The current consensus, developed by experts from India, aims to give recommendations on various frequently raised clinical questions with regards to NOACs and its usage. This practical document provides a platform upon which future guidelines, policies, training, and education for the use of NOACs can be tailored.

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Direct Oral Anticoagulants: From Randomized Clinical Trials to Real-World Clinical Practice

Cited by 48 publications

References 105 publications

Synthesis and Hemostatic Activity of New Amide Derivatives

Synthesis and Hemostatic Activity of New Amide Derivatives

Association of Direct Oral Anticoagulants (DOACs) and Warfarin With Haemorrhagic Risk by Applying Correspondence Analysis to Data From the Italian Pharmacovigilance Database – A Case Study

Expert Recommendations on the Usage of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) from India: Current Perspective and Future Direction

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