Abstract 17252: Rates and Predictors of Co-Prescribing Common Interacting Cardiovascular Medications in Atrial Fibrillation Patients on Direct Oral Anticoagulants

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mohammed Shurrab ◽  
Maria Koh ◽  
Cynthia JACKEVICIUS ◽  
Feng Qiu ◽  
Karen Tu ◽  
...  

Introduction: Amiodarone and diltiazem are commonly prescribed cardiovascular medications in atrial fibrillation (AF) patients who take direct oral anticoagulants (DOACs). They are known to have drug-drug interactions (DDIs) with DOACs, increasing serum levels of DOACs by 40-60%, and potentially increasing risk of bleeding. Objective: To evaluate frequency of use of amiodarone or diltiazem among continuous users of DOACs in AF patients and assess factors associated with their use. Methods: The study population included all AF patients with continuous DOAC use in Ontario, Canada, ≥66 years, from April 1 2017 to March 31 2018. We used linked databases housed at ICES, Ontario. DOAC fill dates and days supplied per prescription were used to determine treatment durations. A maximum gap of 30 days between prescriptions was allowed. Multivariable logistic regression models were used to identify predictors of prescribing amiodarone or diltiazem among AF patients on DOACs. Results: In total, 5390 AF patients, ≥66 years, with continuous DOAC use were identified. Amiodarone was co-prescribed in 343 (6.4%) patients and diltiazem was co-prescribed in 604 (11.2%) patients. The presence of percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) significantly increased the odds of co-prescribing amiodarone among AF DOAC patients (OR 2.52 [95% CI 1.55, 4.10], p=0.0002 and OR 5.19 [95% CI 3.46, 7.80], p= <0.0001, respectively). The presence of chronic obstructive pulmonary disease was associated with significantly increased diltiazem co-prescription among AF DOAC patients (OR 1.55 [95% CI 1.28, 1.87], p=<0.0001) when adjusted for important patient-level factors (Tables 1&2). Conclusions: Among AF patients with continuous DOAC use, the presence of PCI or CABG was associated with increased amiodarone co-prescription. Future efforts should focus on examining the risk of bleeding in these vulnerable populations exposed to major DOAC DDIs.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alexander C Perino ◽  
Krishna Pundi ◽  
Jun Fan ◽  
Susan K Schmitt ◽  
Mitra Kothari ◽  
...  

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p<0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.


2021 ◽  
pp. 106-126
Author(s):  
Т. N. Novikova

This review is devoted to the safety issues of anticoagulant therapy prescribed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Direct oral anticoagulants are considered worldwide in accordance with the guidelines for the diagnosis and treatment of atrial fibrillation as the preferred anticoagulant choice for the prevention of stroke and systemic embolism. Direct oral anticoagulants in comparison with vitamin K antagonists generally have similar efficacy, but different safety profiles, primarily, this concerns the risk of large extracranial and, primarily, gastrointestinal hemorrhages. To minimize the risk of bleeding during therapy with direct oral anticoagulants, an individual approach to the choice of the drug for each individual patient is required after assessing the risk of bleeding, searching for a potential bleeding substrate, correcting existing risk factors and eliminating, if possible, the substrate. When choosing an anticoagulant therapy, special attention should be paid to the most vulnerable categories of patients, such as patients of older age groups and patients with concomitant chronic kidney disease. Among the direct oral anticoagulants registered in the Russian Federation, according to meta-analyzes of key randomized clinical trials and real clinical trials, apixaban has the most optimal benefit: risk ratio in a wide range of patients, including vulnerable populations. Dynamic observation, including regular assessment of renal function, control of clinical blood analysis, erythrocyte and platelet levels, after prescribing an individually selected anticoagulant to the patient, ensures the maximum safety of therapy. Small, so-called, annoying bleeding is not a reason for canceling the anticoagulant, but requires a careful search for the causes of bleeding and their correction.


2021 ◽  
Vol 34 ◽  
pp. 100788
Author(s):  
Mohammed Shurrab ◽  
Maria Koh ◽  
Cynthia A. Jackevicius ◽  
Feng Qiu ◽  
Michael Conlon ◽  
...  

2020 ◽  
pp. 56-64
Author(s):  
E. P. Panchenko

The article presents an analytical review of the studies aimed at determining the optimal antithrombotic therapy in patients with atrial fibrillation undergoing elective or emergency percutaneous coronary intervention (PCI) due to the development of acute coronary syndrome (ACS). The results of the WOEST study are analysed. This study was the first to demonstrate an opportunity to safely discontinue administration of aspirin as part of the multicomponent antithrombotic therapy that included warfarin as an anticoagulant. Three studies were analysed - PIONEER AF-PCI, RE-DUAL-PCI and AUGUSTUS, where direct oral anticoagulants (DOACs) - rivaroxaban, dabigatran and apixaban were used as anticoagulants as part of the multicomponent therapy. The results of these studies formed the backbone of the updated European guidelines for the diagnosis and treatment of atrial fibrillation, 2020. The guidelines offer to divide patients with AF and ACS, who require multicomponent antithrombotic therapy, into two categories. The first group includes AF patients with uncomplicated PCI without a high risk of stent thrombosis, as well as patients with a risk of bleeding that prevails over the risk of stent thrombosis. The second category of patients, in contrast, is characterized by a high risk of stent thrombosis, which prevails over the risk of bleeding. In the absence of contraindications, the patients of both categories should choose DOAC as an anticoagulant and be prescribed clopidogrel as a P2Y12 inhibitor for 12 months. In AF patients with uncomplicated PCI without a high risk of stent thrombosis, as well as in patients with a risk of bleeding, which prevails over the risk of stent thrombosis, the period of treatment with the second antiplatelet drug (aspirin) should belimited to the hospital stay. Patients at increased risk of stent thrombosis and reduced risk of bleeding can extend the aspirin therapy for 1 month. The approaches to the choice of the duration and composition of the multicomponent antithrombotic therapy in AF patients taking oral anticoagulants after elective PCI are similar to those in ACS patients, except for the duration of clopidogrel therapy, which is reduced to 6 months in all patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sampada K Gandhi ◽  
Michael D Ezekowitz ◽  
James A Reiffel ◽  
Rania Boiron ◽  
Mattias Wieloch

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.


2021 ◽  
Author(s):  
Moataz Dowaidar

Thrombosis is the world's leading cause of death, accounting for one of everyfour deaths. Atrial fibrillation is responsible for around a tenth of all ischaemicstrokes (AF) Antiplatelet drugs are the cornerstone of AT treatment andprevention. Long-term use of aspirin and clopidogrel has little advantage overeither agent alone in terms of stroke prevention. It does, however, significantlyraise the risk of bleeding complications. Direct oral anticoagulants are at least aseffective as warfarin in reducing stroke. Return to the tab on which you arrived.Bleeding is the most common side effect of all commercially approvedantiplatelet drugs. Thrombin, thrombine, and thromboembolism are also bloodclotting proteins that are deficient in certain patients to differing degrees.Thrombin is a platelet activator that plays a role in platelet-coagulation pathwaycrosstalk. All coagulated factors, with the exception of FXII, are required forhaemostasis. Extrinsic and typical pathway components are required byhaemostases. The key protease in the coagulation cascade is thrombin. Since thehaemostatic plugs have sealed the wound, the fibrinolytic system separates themfrom the vasculature. Nanomedicine has elegantly attempted to cure differentgene polymorphisms and mutations in complex disorders using gene therapyapproaches.


2020 ◽  
pp. 17-26
Author(s):  
E. S. Kropacheva ◽  
E. P. Panchenko

This review focuses on some aspects of anticoagulant therapy in the updated clinical guidelines for atrial fibrillation of the European society of cardiology, published in 2020. Atrial fibrillation is a polymorbid continuously developing syndrome, and therefore the treatment strategy is based on a comprehensive assessment of the patient, including the risk of stroke, the presence and severity of symptoms, and an assessment of structural heart disease and comorbidities. The review describes the principles of the proposed integrated approach, abbreviated “ABC pathway”, as reflecting the three main directions of the treatment strategy. According to experts, the clinical picture of AF (i.e. first detected, paroxysmal, persistent, long-term persistent or permanent) should not determine the indications for the appointment of anticoagulant therapy. The CHA2DS2-VASc scale continues to be the basis for stratification of thromboembolic risk. The role of dabigatran in primary and secondary prevention of stroke and systemic embolism in patients with atrial fibrillation is described. Changes in the position of experts regarding the assessment of bleeding risk are highlighted in order to help identify unmodified and eliminate modifiable risk factors for bleeding, as well as to identify AF patients who are potentially at high risk of bleeding for more frequent monitoring and monitoring of their condition. Questions about the use of direct oral anticoagulants in the choice of rhythm control tactics are highlighted separately. The use of dabigatran in patients undergoing cardioversion and catheter ablation is justified. Practical questions about the continuous strategy of anticoagulant therapy during ablation are highlighted separately. Changes related to multicomponent therapy after percutaneous coronary intervention are highlighted. The main measure to improve the safety of combined antithrombotic therapy is to minimize the duration of triple therapy. The updated recommendations supportlimiting the duration of triple antithrombotic therapy to 1 month, and also provide for early discontinuation of aspirin (≤1 week) and continuation of double antithrombotic therapy in cases of uncomplicated stenting and low risk of thrombosis, or when the risk of bleeding exceeds the risk of thrombotic events.


2021 ◽  
pp. 106002802199520
Author(s):  
Hannah Whittemore ◽  
Andrew K. Posen ◽  
Erika L. Hellenbart ◽  
Vicki Groo ◽  
Eric Wenzler ◽  
...  

Background: Atrial fibrillation (AF) increases the risk of stroke and direct oral anticoagulants (DOACs) are first-line agents for prevention. Gaps in the literature cause reluctance in prescribing DOACs for patients with renal dysfunction and/or extremes in body weight. Objective: To evaluate the impact body weight and renal function have on major and clinically relevant nonmajor (CRNM) bleeding events and ischemic strokes in AF patients receiving a DOAC. Methods: This retrospective cohort study included adults with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL) receiving a DOAC ≥12 months. The primary outcome was a composite of major and CRNM bleeding events. Secondary outcomes included ischemic stroke and risk factors for bleeding events. Results: Of the 233 patients analyzed, 25 patients experienced a bleeding event. Patients who bled weighed 10 kg less ( P = 0.043) than those who did not and had a higher HASBLED score ( P = 0.003). Multivariate logistic regression identified weight ( P = 0.048), serum creatinine (SCr; P = 0.027), and HASBLED score ( P = 0.024) as the significant predictors for experiencing a bleed. Three patients experienced a stroke. Conclusion and Relevance: This study demonstrates an association between higher baseline SCr, elevated HASBLED score, and lower weight, with an increased risk of bleeding in patients with NVAF or AFL receiving a DOAC. These findings add to prescribing considerations when initiating DOACs. Closer monitoring is advised for patients with significant renal dysfunction and/or low body weight, even with renal dose adjustments.


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