scholarly journals Relevance of physicochemical properties and functional pharmacology data to predict the clinical safety profile of direct oral anticoagulants

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Charles J. Ferro ◽  
Fay Solkhon ◽  
Zahraa Jalal ◽  
Abdullah M. Al‐Hamid ◽  
Alan M. Jones
Keyword(s):  
Physicochemical Properties ◽  
Safety Profile ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Clinical Safety

scholarly journals Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions

2017 ◽  
Vol 83 (7) ◽  
pp. 1532-1543 ◽  
Author(s):  
Luca Monaco ◽  
Chiara Biagi ◽  
Valentino Conti ◽  
Mauro Melis ◽  
Monia Donati ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Safety Profile ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Drug Reactions

Evaluation of cabozantinib (cabo) in combination with direct oral anticoagulants (DOAC) or low molecular weight heparin (LMWH) in renal cell carcinoma (RCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 291-291
Author(s):  
Akram Mesleh Shayeb ◽  
Danielle Urman ◽  
Nazli Dizman ◽  
Luis A Meza ◽  
Akhilesh Sivakumar ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Safety Profile ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Comparable Efficacy ◽  
Fisher Exact Test ◽  
Bleeding Events ◽  
Patients With Cancer ◽  
Number Of Patients ◽  
Major Bleeding Events

291 Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. Despite cabo improving RCC outcomes, VTE management in these patients remains a challenge, partly due to poor understanding of cabo safety profile and drug interactions with anticoagulants. Recent anti-Xa DOAC studies demonstrated comparable efficacy and safety with LMWH for VTE treatment in patients with cancer. Thus far, cabo clinical trials have largely allowed concurrent LMWH use but not DOACs. Herein, we investigated the hemostasis safety profile of cabo with different anticoagulants in patients with RCC. Methods: We performed a retrospective multicenter study (7 sites) of patients with advanced RCC receiving treatment with cabo. Patients were allocated into three groups: cabo with concomitant use (at least 1 week) of 1) DOACs (anti-Xa inhibitors), 2) LMWH, or 3) no anticoagulant. Primary endpoint was to evaluate the rate of major bleeding events (defined per the International Society of Hemostasis and Thrombosis criteria) in the above groups. Secondary endpoint was rate of new/recurrent VTE while on anticoagulation. Overall comparison between groups was analyzed by Fisher exact test. If a difference was found, then pairwise comparison was done. Results: Between 2016-2020, 172 patients with RCC received cabo (DOAC 50, LMWH 18, and no anticoagulant 104). At initiation, cabo median dose was 60 mg but 45% had dose reduction. Median age was 63 [IQR 57-69]. Most were males (77%), had clear cell histology (81.5%), underwent nephrectomy (76.7%), and had intermediate IMDC risk disease (59%). Cabo was first, second, and subsequent line of therapy in 19.8%, 34.9%, and 45.3% of patients, respectively. The table below shows major bleeding and VTE events between groups. An overall difference of major bleeding was found between the three groups comparison ( p=0.009). There was no difference in major bleeding events between patients who received DOAC vs LMWH ( p=0.28) and DOAC vs no anticoagulant ( p=0.1) but there was a difference between LMWH vs no anticoagulant ( p=0.02). Two patients died from bleeding (one in LMWH and one in DOAC group). Conclusions: This study highlights the first reported real world experience of cabo with different anticoagulants in patients with advanced RCC. Cabo use with a DOAC had a similar bleeding risk in comparison to patients not receiving any anticoagulation. In carefully selected patients, DOACs can be considered as concurrent medications in those receiving cabo. Given the low number of patients receiving LMWH, it is difficult to draw conclusions from this group. Data are currently being updated to expand subjects receiving DOAC and LMWH in our cohort. [Table: see text]

scholarly journals 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

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Gaio ◽  
Carmen Ferrajolo ◽  
Alessia Zinzi ◽  
Consiglia Riccardi ◽  
Pasquale Di Filippo ◽  
...  
Keyword(s):  
Correspondence Analysis ◽  
Safety Profile ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Age Distribution ◽  
Cerebral Haemorrhage ◽  
Real World Data ◽  
Total Contribution ◽  
Campania Region ◽  
Pharmacovigilance Database

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.

scholarly journals Safety of Direct Oral Anticoagulants in Patients 75 Years and Older: Comments on the Consensus Opinion of Russian Experts

Medicina ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 1-20
Author(s):  
S. N. Bel'diev ◽  
◽  
I. V. Medvedeva ◽  
I. V. Egorova ◽  
E. I. Berezina ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Safety Profile ◽  
Antithrombotic Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
The Elderly ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Consensus Opinion ◽  
Correct Data

The consensus opinion of Russian experts "Antithrombotic therapy in the elderly and senile age" (2021) contains selective and insufficiently correct data, obtained in randomized controlled trials RE-LY, ROCKET AF, ARISTOTLE and ENGAGE AF-TIMI 48. As a result, it makes the impression that dabigatran 150 mg twice daily showed the least safety compared to warfarin in patients 75 years or older. This paper presents the corrected and supplemented data of the ROCKET AF trial, indicating that in patients 75 years or older rivaroxaban compared with warfarin showed no better safety profile than dabigatran 150 mg twice daily in the RE-LY trial.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

VASA ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 87-95 ◽  
Author(s):  
Giovanna Elmi ◽  
Giuseppe Di Pasquale ◽  
Raffaele Pesavento
Keyword(s):  
Venous Thromboembolism ◽  
Safety Profile ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Recurrence ◽  
Extended Treatment

Abstract. As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

scholarly journals Elderly Patients with Atrial Fibrillation: Focus on Comorbidity and Safety of Anticoagulant Therapy

2019 ◽  
Vol 15 (4) ◽  
pp. 553-557 ◽  
Author(s):  
D. A. Napalkov ◽  
A. A. Sokolova
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Anticoagulant Therapy ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Systemic Embolism ◽  
Good Adherence ◽  
Younger Patients

The article discusses issues related to the prescription of anticoagulant therapy to elderly patients with atrial fibrillation (AF), especially those over 70 and 80 years of age. The relevance of the issue is primarily due to the prevalence of AF in this cohort of patients, and the second is due to the higher incidence of comorbidity. The presented material demonstrates the peculiarities of anticoagulant therapy application in groups of patients older than 75, based on the data of randomized clinical trials, and also presents extrapolation of the results of RCTs to the real clinical practice (data of registers and cohort trials). The use of unreasonably low doses of oral anticoagulants in elderly patients is debated. It often leads to a decrease in the efficacy of anticoagulant therapy without improving the drugs safety profile. A new validated scale (ABH) for evaluating of anticoagulant therapy safety is presented in the article. The ABH scale can be used before prescribing to patients exactly direct oral anticoagulants. This scale is simpler and more practical than the HAS-BLED scale. The data for the ABH scale are validated based on direct oral anticoagulants in 21,248 patients from the Norwegian register. The presented results demonstrate a favorable efficiency and safety profile of rivaroxaban in comparison with warfarin in patients 75 years and older. Thus, the overall benefit for the use of rivaroxaban against warfarin in patients > 75 years of age in the subanalysis of the ROCKET-AF study was statistically significantly greater than in younger patients with AF. Data on 11121 patients with AF who were treated with rivaroxaban for the prevention of stroke and systemic embolism are included in the combined analysis of the XANTUS, XANAP and XANTUS-EL registers. 96% of patients in the study did not have serious thromboembolic events. The amount of major bleeding was 1.7 per 100 patient-years, and gastrointestinal bleeding was 0.7 per 100 patient-years. This turned out to be less than in some other registry studies. In addition, patients showed good adherence to rivaroxaban treatment: after a year, 77.4% of patients continued to take the drug.

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