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.

458Real world persistence with direct oral anticoagulants in anticoagulation naive patients with atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G Denas ◽  
G Costa ◽  
E Ferroni ◽  
N Gennaro ◽  
U Fedeli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cox Regression ◽  
Anatomical Therapeutic Chemical ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Female Gender ◽  
Population Based ◽  
Real World Data

Abstract Introduction Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications. Purpose To assess persistence levels of DOACs and look for possible predictors of treatment discontinuity in NVAF patients. Methods We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression. Results Overall, 17920 patients initiated anticoagulation with DOACs in the study period. Most patients were older than 74 years old, while gender was almost equally represented. Comorbidities included hypertension (72%), diabetes mellitus (17%), congestive heart failure (9%), previous stroke/TIA (20%), and prior myocardial infarction (2%). After one year, the persistence to anticoagulation treatment was 82.7%, while the persistence to DOAC treatment was 72.9% with about 10% of the discontinuations being due to switch to VKAs. On multivariate analysis, factors negatively affecting persistence were female gender, younger age (<65 years), renal disease and history of bleeding. Conversely, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction. Persistence to DOAC therapy Conclusion This real-world data show that within 12 months, one out of four anticoagulation-naïve patients stop DOACs, while one out of five patients stop anticoagulation. Efforts should be made to correct modifiable predictors and intensify patient education.

scholarly journals Adverse Drug Reactions during Real-Life Use of Direct Oral Anticoagulants in Italy: An Update Based on Data from the Italian National Pharmacovigilance Network

2020 ◽  
Vol 10 (4) ◽  
pp. 266-276 ◽  
Author(s):  
Carlo Lavalle ◽  
Luca Di Lullo ◽  
Antonio Bellasi ◽  
Claudio Ronco ◽  
Stefano Radicchia ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Market Share ◽  
Adverse Drug Reactions ◽  
Oral Anticoagulants ◽  
Risk Index ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Drug Reactions ◽  
Safety And Efficacy ◽  
Pharmacovigilance Database

Background: The availability of direct oral anticoagulants (DOAC) in clinical practice has transformed the health care provided to patients for the prevention and treatment of thromboembolism. Safety and efficacy data guide clinicians in the choice of the drug used. To date, no evidence is available from head-to-head trials comparing different DOAC with regard to safety and efficacy; information is mainly derived from several meta-analyses and real-life studies. Conclusions from these studies are inconsistent and unsatisfactory. The evaluation of self-reported adverse drug reactions (ADR) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision-making. Objective: To analyze potential suspected ADR of DOAC using a previously described risk index (RI) in daily clinical practice in Italy. Methods: The National Pharmacovigilance Network database (from the AIFA website) was searched in order to retrieve information on all ADR related to oral anticoagulants occurring from 2013 to 2018. The ADR RI for each drug was calculated, where an RI = 1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (safer DOAC). The following DOAC molecules were considered: dabigatran, rivaroxaban, apixaban, and edoxaban. Results: The results showed that rivaroxaban is the DOAC with the lowest RI among the 4 molecules available today in Italy. Conclusions: Based on the RI, we identified rivaroxaban as the DOAC having the best safety profile.

scholarly journals The use and adherence of oral anticoagulants in Primary Healthcare in Catalunya: a real-world data cohort study

2019 ◽  
Author(s):  
Maria Giner-Soriano ◽  
Jordi Cortes ◽  
Ainhoa Gomez-Lumbreras ◽  
Oriol Prat-Vallverdú ◽  
Mª Angeles Quijada-Manuitt ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stroke Prevention ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Platelet Aggregation Inhibitors ◽  
Population Based ◽  
Real World Data ◽  
Implementation Phase ◽  
Aggregation Inhibitors ◽  
Data Source

Abstract Background The use of direct oral anticoagulants (DOAC) for stroke prevention in non-valvular atrial fibrillation (NVAF) has not been previously assessed in our setting. We aimed to describe sociodemographic, comorbidities, co-medication and risk of thromboembolic events and bleeding in patients with NVAF initiating oral anticoagulants (OAC) for stroke prevention, and to estimate adherence and persistence to OAC.Methods Population-based cohort study including all NVAF adult patients initiating OAC for stroke prevention in August 2013-December 2015. Persistence was measured in patients initiating OAC in August 2013-December 2014. Data source is SIDIAP, which captures electronic health records from Primary Health Care in the Catalan Health Institute, covering approximately 5.8 million people.Results 51,690 NVAF patients initiated OAC; 47,197 (91.3%) were naive to OAC and 32,404 initiated acenocoumarol (62.7%). Mean age was 72.8 years (SD 12.3) and 49.4% were women. Platelet-aggregation inhibitors were taken by 9,105 (17.6%) of the patients. For 22,075 patients, persistence was higher among the non-naive patients [n=258 (61.7%)] than among the naive [n=11,502 (53.1%)]. Adherence was estimated for patients initiating DOAC and was similar in naive and non-naive patients. Among the naive to DOAC treatment, those starting rivaroxaban showed a highest proportion [(n=360 (80.1%)] of good adherence at implementation (MPR>80%) while patients starting dabigatran were less adherent [n= 203 47.8%)].Conclusions Acenocoumarol was the most frequently prescribed OAC as first therapy in NVAF patients. Non-naive to DOAC showed better persistence than naive. Rivaroxaban showed higher proportion of adherent patients during the implementation phase than apixaban and dabigatran the lowest.

Direct Oral Anticoagulants Plasma Levels Measurement: Clinical Usefulness from Trials and Real-World Data

2021 ◽  
Vol 47 (02) ◽  
pp. 150-160
Author(s):  
Francesca Renon ◽  
Anna Rago ◽  
Biagio Liccardo ◽  
Antonello D'Andrea ◽  
Lucia Riegler ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Plasma Levels ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Outcome Data ◽  
Bleeding Events ◽  
Real World Data ◽  
World Data ◽  
Emergency Situations

AbstractMeasurement of direct oral anticoagulants (DOACs) activity is not routinely necessary. Indeed, evaluation of DOACs plasmatic concentration is discouraged for the majority of patients, due to the lack of outcome data supporting this approach. Nevertheless, DOAC measurements may be useful in emergency situations such as serious bleeding events, need for urgent invasive procedures, and acute ischemic stroke or in managing anticoagulation in “special populations” not adequately studied in clinical trials, for example the very elderly or those at the extremes of body weight. The aim of this review is to describe and summarize the methods for DOACs activity evaluation and the settings in which their plasma level measurement may be indicated, analyzing indications from scientific societies and evidence from clinical trials, as well as real world data on the usefulness of DOACs plasma levels “monitoring.”

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

scholarly journals Detection of direct oral anticoagulants with the dilute Russels viper venom time – observations in a real life setting

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Kloeter ◽  
T Siegemund ◽  
A Siegemund ◽  
U Laufs ◽  
S Petros ◽  
...  
Keyword(s):  
Real World ◽  
Plasma Levels ◽  
Lupus Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Public Institution ◽  
Peak Time ◽  
Real World Data ◽  
Screening Assay

Abstract Background The detection of direct oral anticoagulants (DOACs) in emergency settings still remains challenging, especially when dedicated anti-Xa or anti-IIa tests are not readily available or the specific DOAC is unknown. The dilute Russel's viper venom time (dRVVT) is widely known in lupus anticoagulant (LA) testing and may also provide helpful information regarding the residual antithrombotic activity of DOACs. Yet real world data describing the effect of DOACs on the dRVVT is scarce. Objective The study aimed to evaluate the sensitivity and specificity of dRVVT for different DOAC plasma levels. Methods A total of 80 patients were recruited – 20 patients for each approved DOAC (apixaban, edoxaban, rivaroxaban and dabigatran). Blood plasma was sampled before (baseline), 6 and 12 hours after DOAC-intake and at plasma peak time. DRVVT was measured using the LA1 screening assay for lupus anticoagulant. Plasma levels were measured by calibrated anti-Xa or anti-IIa tests. Additionally, activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured. Results All DOACs significantly prolonged the dRVVT. The effects were more pronounced at higher DOAC plasma levels. The area under the receiver operating characteristic (ROC) curve regarding a plasma level cut-off of 30 ng/ml was 0.92 (95% confidence interval (CI) 0.823 to 1.00) for apixaban, 0.97 (95% CI 0.902 to 1.00) for edoxaban, 0.87 (95% CI 0.649 to 1.00) for rivaroxaban and 0.96 (95% CI 0.871 to 1.00) for dabigatran. Conclusion A dose dependent effect of all approved direct oral anticoagulants (DOACs) on the dilute Russel's viper venom time (dRVVT) was documented in our real world setting, while relevant DOAC plasma levels did not affect standard coagulation tests. The negative predictive value for the dRVVT was high even at low DOAC plasma levels. The dRVVT could therefore be helpful to rule out relevant antithrombotic plasma activity caused of DOACs in emergency situations. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Universität Leipzig Figure 1. ROC curves

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]

Characterizing safety and efficacy in ovarian cancer patients with thromboembolism treated with rivaroxaban.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18720-e18720
Author(s):  
Christine G. Kohn ◽  
Jonathan T. Caranfa ◽  
Molly Brewer ◽  
Meghana Singh ◽  
Craig I. Coleman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real World Data ◽  
Emergency Department Admission ◽  
Significant Difference ◽  
Treatment Analysis

e18720 Background: There is a paucity of real-world data regarding rates of recurrent venous thromboembolism (VTE), major bleeding and all-cause mortality among ovarian cancer patients with thrombosis treated with direct oral anticoagulants (DOACs) currently available. We sought to evaluate the effectiveness and safety of rivaroxaban versus low molecular-weight heparin (LMWH) for cancer-associated thrombosis (CAT) treatment in patients with ovarian cancer. Methods: We utilized US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013-2016 to identify adults with active ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Rivaroxaban and LMWH cohorts were balanced using propensity score overlap weighting . Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately and mortality at six-months using an intention-to-treat approach. On-treatment analysis after 12-months was also performed. Hazard ratios (HRs) with 95% confidence intervals using overlap weighted cox regression were reported. Results: We included 33 rivaroxaban and 92 LMWH-managed CAT patients. In each cohort, mean age was 73, 79.5% of patients were white, 46.9% had a history of ≥ stage 3 chronic kidney disease (CKD), two-thirds had metastatic disease at the time of VTE, and 32.6% had a prior VTE. Patients were diagnosed with ovarian cancer an average of 1.40 years prior to the index VTE event and 45.8% had a pulmonary embolism (with or without DVT) as the index event. Our analysis did not detect a significant difference in outcomes with rivaroxaban versus LMWH at six-months (Table). On-treatment analysis at 12-months showed similar results. Conclusions: Rivaroxaban may be a reasonable alternative to LMWH for CAT patients with ovarian cancer. Large observational studies are needed to confirm these results.[Table: see text]

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