Impact of medication adherence on risk of ischemic stroke, major bleeding and deep vein thrombosis in atrial fibrillation patients using novel oral anticoagulants

Abstract Introduction Direct acting oral anticoagulants are rapidly replacing warfarin, the most commonly used anticoagulant for patients with atrial fibrillation, pulmonary embolism (PE) and deep vein thrombosis (DVT). However, there is limited data on the efficacy and adverse effects of the commercial Kcentra used in these patients. Kcentra, the only approved PCC in the USA, is FDA approved for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy in adult patients with acute major bleeding or need for an urgent surgery/invasive procedure. In this study we examine the indications for administration of Kcentra, efficacy of the PCC in several coagulopathies, incidence of adverse events including ischemic stroke and DVT/ PE, and overall mortality. Methods Retrospective analysis of inpatients at UPMC Presbyterian, Shadyside and Mercy, admitted between February 2016 and 2017 was done. A total of 213 patients, with history of stroke / DVT / PE who received Kcentra were grouped based on the cause of coagulopathy, sites of bleed (CNS or non-CNS) or the clinical setting of Kcentra administration. Definitions of the International Society on Thrombosis and Hemostasis (ISTH) / Scientific and Standardization Committee were used to assess the efficacy of management. Among the patients on Warfarin, only non-CNS and prophylactic administration group were included here as those with CNS bleeding were part of an earlier study. Adverse events measured were incidence of ischemic stroke and DVT/ PE during their hospital stay. Results The 213 patients who received Kcentra included those on warfarin (40%), apixaban (21%), Rivaroxaban (23%), with the remaining 16% including patients with hepatic cirrhosis, disseminated intravascular coagulation and those with coagulopathy related to heparin/ fondaparinux or antiplatelets (ASA, clopidogrel). The study group included those with CNS bleeds (33%), non-CNS bleeds (37%) and those in the prophylactic, pre-operative setting (30%). The majority of the non-CNS bleeds were patients with gastrointestinal bleeding (45%), with the rest including the musculoskeletal (31%) and intra-abdominal / intra-thoracic (16%) bleeding. Mortality was highest in patients with cirrhosis (n = 15), DIC (n = 8), and on anti-platelet medications (n = 2) at 100%, followed by 60% in patients on heparin / fondaparinux (n = 5). The mortality was markedly lower (~13%) in patients on Coumadin, Apixaban and Rivaroxaban. 2 of the patients, previously on rivaroxaban, developed multiple CNS infarcts. Thromboembolic events were significantly higher (40%) in patients with cirrhosis, with moderate effect in the Rivaroxaban group (14.5%) when compared to coumadin (2.3%) and apixaban (0%). Conclusions Kcentra was used in several off-label clinical settings, with comparable mortality among the coumadin, rivaroxaban and apixaban groups and no identifiable benefit in the setting of cirrhosis, DIC or antiplatelet medications, but with an increased incidence of deep vein thrombosis and stroke. Disclosures No relevant conflicts of interest to declare.

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Safety and feasibility of rivaroxaban in deferred workup of patients with suspected deep vein thrombosis

Blood Advances ◽

10.1182/bloodadvances.2020001556 ◽

2020 ◽

Vol 4 (11) ◽

pp. 2468-2476

Author(s):

Synne G. Fronas ◽

Anders E. A. Dahm ◽

Hilde S. Wik ◽

Camilla T. Jørgensen ◽

Jostein Gleditsch ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Secondary Outcome ◽

Vein Thrombosis ◽

Compression Ultrasound ◽

Therapeutic Doses ◽

Deep Vein

Abstract Guidelines suggest using empiric low-molecular-weight heparin if the diagnostic workup of deep vein thrombosis (DVT) is expected to be delayed. The role of direct oral anticoagulants for deferred compression ultrasound imaging (CUS) in patients with suspected DVT remains unexplored. The main objective of the study was to assess the safety of deferring CUS with therapeutic doses of rivaroxaban. We prospectively included consecutive outpatients referred to the Emergency Department at Østfold Hospital, Norway, with suspected first or recurrent lower-extremity DVT between February 2015 and November 2018. Patients were discharged with rivaroxaban 15 mg twice daily while awaiting CUS within 24 hours if D-dimer level was ≥0.5 mg/L fibrinogen-equivalent units. The primary outcome was the rate of major bleeding incidents from study inclusion until DVT was confirmed and anticoagulation therapy continued, or otherwise up to 48 hours following administration of the last tablet of rivaroxaban. The secondary outcome was the rate of progressive DVT symptoms or symptoms or signs of pulmonary embolism between hospital discharge until venous thromboembolism was diagnosed. Six hundred twenty-four of 1653 patients referred with suspected DVT were included (37.7%; 95% confidence interval [CI], 35.4-40.1). DVT was diagnosed in 119 patients (19.1%; 95% CI, 16.1-22.3). There were no major bleeding incidents, yielding an observed major bleeding rate of 0% (1-sided 95% CI <0.4). No patients experienced major complications in the interval that CUS was deferred (0%; 95% CI, 0.0-0.6). Deferring CUS for up to 24 hours in patients with suspected DVT with therapeutic doses of rivaroxaban is a safe strategy. This trial was registered at www.clinicaltrials.gov as #NCT02486445.

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Rivaroxaban Causing Thrombocytopenia in a Case of Deep Vein Thrombosis (DVT)

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/548 ◽

2021 ◽

Vol 10 (32) ◽

pp. 2687-2688

Author(s):

Twinkle Pawar ◽

Yash Gupte ◽

Sourav Chaturvedi ◽

Anusha Gupta ◽

Sourya Acharya

Keyword(s):

Deep Vein Thrombosis ◽

Oral Anticoagulants ◽

Factor Xa ◽

Gastrointestinal Haemorrhage ◽

Cerebral Haemorrhage ◽

Systemic Circulation ◽

Novel Oral Anticoagulants ◽

Vein Thrombosis ◽

Rare Case Report ◽

Deep Vein

Novel oral anticoagulants (NOACs) are used as alternative to intravenous anticoagulants. It includes apixaban, dabigatran, rivaroxaban and edoxaban.1 Some of the complications induced by these drugs are gastrointestinal haemorrhage, cerebral haemorrhage and rarely thrombocytopenia. We present a rare case report of a selective factor Xa inhibitor rivaroxaban, which induced thrombocytopenia in a case of deep vein thrombosis (DVT) of right lower limb. Drugs commonly used to prevent embolization of systemic circulation are warfarin and novel oral anticoagulants, such as rivaroxaban and dabigatran.

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Oral Anticoagulants Preference in Hospitalized Patients with Acute Deep Vein Thrombosis or Non-Valvular Atrial Fibrillation

Healthcare ◽

10.3390/healthcare8040404 ◽

2020 ◽

Vol 8 (4) ◽

pp. 404

Author(s):

Ştefan Cristian Vesa ◽

Sonia Irina Vlaicu ◽

Sorin Crișan ◽

Octavia Sabin ◽

George Saraci ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Disease ◽

Deep Vein Thrombosis ◽

Ischemic Heart Disease ◽

Oral Anticoagulants ◽

Lower Limbs ◽

Ischemic Heart ◽

Vein Thrombosis ◽

Deep Vein

(1) Aim: The aim of this study was to assess the preferences of oral anticoagulants (OA) in patients diagnosed with deep vein thrombosis (DVT) of lower limbs or non-valvular atrial fibrillation (AF) requiring anticoagulation for medium/long term. (2) Materials and methods: the study included consecutive patients admitted with a diagnosis of either acute DVT of lower limbs (without signs of pulmonary embolism) or non-valvular AF who required oral anticoagulation, in a time frame of 18 months from January 2017 until June 2018. The following data were recorded: demographic variables, comorbidities (ischemic heart disease, arterial hypertension, heart failure, stroke, peripheral artery disease, diabetes mellitus, obesity), type and dose of OA (acenocoumarol, dabigatran, apixaban, rivaroxaban), complications due to the use of OA. (3) Results: AF patients were older and had considerably more cardiovascular comorbidities than DVT patients. Vitamin K antagonists (VKA) were more likely to be administered in patients with AF, as they had indication for indefinite anticoagulation. VKA were more frequently prescribed in patients with ischemic heart disease, heart failure, and diabetes compared with DVT patients. Moreover, complications related to OA use were more frequent in the VKA group. Almost half of patients with acute DVT (48.5%) were treated with direct OA (DOAC) rather than VKA, and only a quarter of AF patients (24.8%) were treated with DOACs.

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Trial of Aspirin and RA 233 in Prevention of Post-operative Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649098 ◽

1973 ◽

Vol 30 (01) ◽

pp. 018-024 ◽

Cited By ~ 8

Author(s):

Edward H. Wood ◽

Colin R.M. Prentice ◽

D. Angus McGrouther ◽

John Sinclair ◽

George P. McNicol

Keyword(s):

Deep Vein Thrombosis ◽

Controlled Trial ◽

Oral Anticoagulants ◽

Antithrombotic Agent ◽

Fractured Neck Of Femur ◽

Neck Of Femur ◽

Vein Thrombosis ◽

Effective Prophylaxis ◽

Deep Vein ◽

Calf Vein

SummaryAlthough the oral anticoagulants provide effective prophylaxis against postoperative deep vein thrombosis following fracture of neck of femur there is a need for an antithrombotic agent which needs less laboratory control and does not cause haemorrhagic complications. It has been suggested that drugs causing inhibition of platelet function may fulfil these requirements. A controlled trial was carried out in which aspirin, RA 233, or a combination of these drugs was compared with a placebo in the prevention of post-operative deep vein thrombosis. In thirty patients undergoing surgery for fractured neck of femur the incidence of post-operative calf vein thrombosis, as detected by 125I-fibrinogen scanning, was not significantly different between the untreated and treated groups.

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Congenital Antithrombin III Deficiency in 3 Families (7 Affected Members)

10.1055/s-0038-1665841 ◽

1979 ◽

Author(s):

J. Conard ◽

M. Samama ◽

M. H. Horellou ◽

B. Cazenave ◽

P. Griguer ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Antithrombin Iii ◽

Oral Anticoagulants ◽

Vena Cava ◽

Oral Contraception ◽

Vein Thrombosis ◽

Heparin Treatment ◽

At Iii ◽

Antithrombin Iii Deficiency ◽

Deep Vein

A congenital Antithrombin III (AT III) deficiency affecting 7 members of 3 families is reported.The first throrabo-embolic accidents were observed between the age of 22 and 35 : they were spontaneous or occured after delivery or oral contraception. in one patient, a deep vein thrombosis was observed during heparin treatment. in 2 cases, recurrent pulmonary embolic episodes required vena cava ligation. No thromboembolic accident was observed during oral anticoagulation.AT III was measured by an amidolytic method and by the Mancini method on plasma and serum ; the antithrombin activity was determined on serum by the von Kaulla method. in 7 patients, a decreased AT III was found by all the methods performed. The AT III level was around 50 % in patients treated or not by oral anticoagulants One patient was studied during heparin treatment and then under oral anticoagulants : AT III levels were lower under heparin.

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Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.2431 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Giustozzi

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Primary Outcome ◽

Oral Anticoagulants ◽

Early Recurrence ◽

Optimal Timing ◽

Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

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The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

TH Open ◽

10.1055/s-0040-1721499 ◽

2020 ◽

Vol 04 (04) ◽

pp. e417-e426

Author(s):

Carline J. van den Dries ◽

Sander van Doorn ◽

Patrick Souverein ◽

Romin Pajouheshnia ◽

Karel G.M. Moons ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Routine Care ◽

P Value ◽

Risk Of Mortality ◽

Mortality Effect

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

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