Outcomes of Patients with Extended Anticoagulation Using Low Dose Doacs Compared to Standard Therapeutic Anticoagulation

Abstract Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at the therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unknown. Aims: Evaluate the efficacy of reduced-dose DOACs compared to standard therapeutic anticoagulation in patients with extended anticoagulation. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st , 2013 to December 31st, 2020. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Type of anticoagulation and dose changes were recorded, and progressing to a low dose was treated as an endpoint. In the models relating it to the outcome, it was treated as a time-dependent covariate in the cox models. After completing standard anticoagulation treatment for 3 months with any anticoagulant, patients continuing anticoagulation were divided into two groups: standard therapeutic anticoagulation (any drug) vs those who transitioned to rivaroxaban 10 mg daily or apixaban 2.5mg twice daily any time after 3 months. Patients with recurrent VTE, major or CRNMB during the first 3 months were excluded from further analysis. Results: 219 patients (153 on Apixaban and 66 on Rivaroxaban) were identified in the low dose DOAC and 2521 in the standard anticoagulation group. The mean age was 60.7 years, mean weight was 93.2 Kg and 55.9% were males (Table 1). Patients on low dose DOACs were about the same age and weight compared to standard anticoagulation group. Among all diagnosis categories, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; P<0.001), while low dose DOACs prescription was more likely in patients with pulmonary embolism (HR 1.45; 95%CI 1.11-1.89; P=0.007). The median months to start a low dose DOAC after completing the 3 months was 3.1 months with standard deviation of 6.6 months and interquartile range 2.8 months. There was no statistically significant association in the likelihood of going to a low dose group in relation to VTE recurrence (HR 1.36; 95%CI 0.42-4.45; P=0.61) or major bleeding (HR 0.59; 95%CI 0.08-4.37; P=0.61). However, transitioning to low dose DOAC was associated with reduced mortality (HR 0.53; 95%CI 0.35-0.80; P=0.003). Also, patients on low dose DOACs were more likely to have a CRNMB (HR 2.76; 95%CI 1.15-6.62; P=0.02). Conclusion: In this study of patients continuing anticoagulation past 3 months for an initial acute venous thromboembolic event, transitioning to low dose DOACs was not associated with any statistically significant association with VTE recurrence or major bleeding. However, mortality was lower and CRNMB was higher in this unadjusted analysis. Our results show that physicians are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients. Further research is needed to better understand the higher risk for CRNMB identified in this group. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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The Effectiveness and Safety of Direct Oral Anticoagulants (DOACs) Vs. Traditional Anticoagulants in Patients with Cirrhosis

Blood ◽

10.1182/blood.v128.22.5015.5015 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5015-5015

Author(s):

Justin Hum ◽

Janice Jou ◽

Thomas G. Deloughery ◽

Joseph Shatzel

Keyword(s):

Major Bleeding ◽

Conflicts Of Interest ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Complications ◽

Efficacy And Safety ◽

Recurrent Thrombosis ◽

Bleeding Events ◽

Cirrhotic Patients

Abstract Introduction: The coagulopathy associated with cirrhosis is complex and places patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have been shown to have superior efficacy and safety compared to vitamin K antagonists; however their efficacy and safety in cirrhotic patients is not clear. The aim of this study is to retrospectively compare the effectiveness and bleeding complications of DOACs as compared to traditional anticoagulants in cirrhotic patients. Methods: This study was a retrospective review of patients treated at a single academic center between 2012-2015 who were prescribed a DOAC (apixaban or rivaroxaban), or a traditional anticoagulant (warfarin or low molecular weight heparin), with an ICD-9 code for the diagnosis of cirrhosis. The primary outcomes of interest are recurrent thrombosis or stroke (efficacy failure), or bleeding events (safety failure). Major bleeds were characterized as fatal bleeding, symptomatic bleeding in critical organ area, or bleeding causing a fall in hemoglobin level >2 or leading to transfusion of 2+ units of packed red blood cells. Results: During the study period, 27 cirrhotic patients were prescribed a DOAC and 18 were prescribed a traditional anticoagulant (either LMWH or warfarin). Both groups had similar total bleeding events (8 DOAC vs. 10 traditional anticoagulation, p = 0.12). There were significantly less major bleeding episodes in the DOAC group, (1 (4%) vs. 5 (28%), p = 0.03) and less intracranial bleeding (3 (17% ) vs. 0 (0%) p=0.06). Recurrent thrombosis or stroke occurred in 1 (4%) patient in the DOAC group and 1 (6%) patient in the traditional group (p = 1.0). Conclusions: Anticoagulation with DOACs in cirrhotic patients may be as safe as traditional anticoagulants with respect to bleeding events. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or recurrent thrombosis. Table Table. Disclosures No relevant conflicts of interest to declare.

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Direct Oral Anticoagulants in Patients with Cirrhosis Appear Safe and Effective

Blood ◽

10.1182/blood.v128.22.3827.3827 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3827-3827 ◽

Cited By ~ 5

Author(s):

Paul R Kunk ◽

Hampton Collins ◽

Surabhi Palkimas ◽

Nicolas M Intagliata ◽

Hillary S. Maitland

Keyword(s):

Atrial Fibrillation ◽

Liver Injury ◽

Adverse Events ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Therapeutic Anticoagulation ◽

Class B ◽

Repeat Imaging

Abstract Introduction: Patients with cirrhosis have historically been excluded from clinical trials of anticoagulant therapies due to concerns about safety. While erroneously thought to be "auto-anticoagulated," patients with cirrhosis may actually be at increased risk for venous thromboemboli (VTE) due to an imbalance in pro coagulant and anticoagulant factors and do require therapeutic anticoagulation when thrombotic events occur. Traditionally low molecular weight heparins, and less commonly warfarin, have been the anticoagulants of choice in cirrhotic patients, though there are challenges with their use due to difficulty with access, administration and blood monitoring. Direct Oral Anticoagulants (DOACs) are increasingly replacing warfarin for the treatment of VTE and for stroke prevention in non-valvar atrial fibrillation. The administration and standardized dosing make DOACs an attractive alternative for safe and effective therapeutic anticoagulation but very little evidence exists for their use in patients with cirrhosis. Methods: We designed a retrospective analysis of all patients with cirrhosis at the University of Virginia who were treated with a DOAC between January 2012 and May 2016 for all indications. All patients were required to be treated with a DOAC with documented follow up for assessment of adverse events. Medical charts were reviewed for age, gender, weight, cirrhosis etiology, DOAC, dose, indication and length of treatment, Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, bleeding events and appearance of thrombus on repeat imaging. All bleeding events were recorded and graded according the Common Toxicity Criteria for Adverse Events, v4.0. Major bleeding events were reviewed by all investigators. Results: Eighty patients were identified, with 11 patients excluded after not starting a DOAC or being mislabeled as cirrhosis, leaving 69 patients for analysis. Median age was 73 years old (range 44-92) with 77% male. The most common etiologies of cirrhosis were NASH (66%) and HCV (22%). Thirty seven patients (54%) were treated with apixaban, 25 (36%) were treated with rivaroxaban and 7 (10%) were treated with dabigatran. Median length of time on anticoagulation was 6 months. Sixty-eight percent were treated for non-tumoral PVT or DVT while 32% were treated for stroke prevention in atrial fibrillation. Most patients had well compensated cirrhosis, but several had advanced cirrhosis (CTP class A/B/C: 33/26/10). Fourteen percent had an underlying malignancy, most commonly hepatocellular carcinoma, and 52% had esophageal varices. Of those treated for atrial fibrillation, none developed a clot while on a DOAC. Of those treated for VTE, 81% had resolution, 13% unchanged and 6% progression of their clot on repeat imaging. No patient developed drug induced liver injury or discontinued anticoagulation due to liver injury. Sixteen patients (23%) suffered a bleeding event, mostly epistaxis and easy bruising. Major bleeding, defined as grade 3 or higher, occurred in 12% of patients. Most major bleeding was gastrointestinal bleeding; with most but not all requiring endoscopy and transfusions. One subdural hematoma occurred. No variceal bleeding occurred, despite that majority of patients having esophageal varices identified on endoscopy. Of those with major bleeding, all were CTP class B or C with an average MELD of 22, compared to an average MELD of 14 in patients without major bleeding. All patients with major bleeding were treated with either apixaban or rivaroxaban. Conclusion: Similar to other anticoagulants, DOACs should be used with caution in patients with cirrhosis, particularly CTP class B or C. In this case series, the largest to our knowledge, direct oral anticoagulants in patients with cirrhosis compare favorably to historical controls (Delgado, Clin Gastroenterol Hepatol. 2012 Jul;10(7):776-83) with lower incidence of major bleeding and increased clot resolution. Further prospective studies are needed in this at risk and under studied patient population. Table Table. 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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The Role of Direct Oral Anticoagulants in Antiphospholipid Syndrome

Blood ◽

10.1182/blood-2019-128057 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3680-3680

Author(s):

Mohammed Abdullah Alsheef ◽

Mukhtar Alomar ◽

Ohoud Alarfaj ◽

Hussam A AlHamidi ◽

Abdul Rehman Z. Zaidi

Keyword(s):

Antiphospholipid Syndrome ◽

Major Bleeding ◽

Conflicts Of Interest ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Double Positive ◽

Unusual Site ◽

Pregnancy Morbidity ◽

Single Positive ◽

Age Range

Background Antiphospholipid Syndrome (APS) is defined by thrombosis and/or pregnancy morbidity in patients with antiphospholipid antibodies (aPL). There remains a pressing need for identification of clinical and laboratory parameters that define patients at most considerable risk for APS-related events on Direct oral anticoagulants (DOACs). Aims To demonstrate the efficacy and safety of DOAC (Rivaroxaban) compared with Warfarin (Vitamin K Antagonist) in patients with thrombotic APS. Methods A retrospective cohort study of thrombotic APS patients who were started on anticoagulant therapy, either VKA or DOAC, from 2010 -2016. Results We investigated 73 patients diagnosed with APS. 83.5% of the patients were female. The age range at diagnosis was between 26-40 (52%). 67% of the cases were diagnosed in the form of DVT while the rest had arterial or unusual site venous thrombosis. 43% of the patients had systemic lupus disease. 28% of the cases had a single-positive aPL profile, 23% had double-positive, and 49% had triple-positive aPL. 68.5% of the cases were treated with warfarin, while 31.5% of the cases were switched from warfarin to Rivaroxaban. 15% of patients had major and clinically relevant non-major bleeding (2 patients had major bleeding in the warfarin group, and four patients in the rivaroxaban group). Recurrence of thrombosis (arterial and venous) was 43% with Rivaroxaban and 30% with warfarin. The average duration from starting Rivaroxaban to development of complications such as bleeding and thromboembolic events was mostly after 1-2 years (70%). Conclusions Rivaroxaban should be used with extreme caution in APS patients, especially patients with a full positive aPL profile and arterial thrombosis. Disclosures No relevant conflicts of interest to declare.

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A Review on the Use of Reversal Agents of Direct Oral Anticogulant Drugs in Case of Gastrointestinal Bleeding

Reviews on Recent Clinical Trials ◽

10.2174/1574887115666200624193938 ◽

2020 ◽

Vol 15 ◽

Author(s):

Veronica Ojetti ◽

Angela Saviano ◽

Mattia Brigida ◽

Luisa Saviano ◽

Alessio Migneco ◽

...

Keyword(s):

Gastrointestinal Bleeding ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medical Emergency ◽

Management Approach ◽

Emergency Setting ◽

Reversal Agents ◽

Life Threatening ◽

Andexanet Alfa

Background : Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant’s intake. Anticoagulants are commonly used for the prevention and the treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, betrixaban) showed a better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke. Literature data reported a high risk of gastrointestinal bleeding with DOACs, in particular with dabigatran and rivaroxaban. In case of life-threatening gastrointestinal bleeding, these patients could benefit from the use of reversal agents. Methods: We performed an electronic search on PUBMED of the literature concerning reversal agents for DOACs and gastrointestinal bleeding in the Emergency Department from 2004 to 2020. AIM: This review summarizes the current evidences about three reversal agents idarucizumab, andexanet alfa and ciraparantag, and the use of the first two in the emergency setting in patients with an active major bleeding or who need urgent surgery to offer physicians indications for a better management approach in order to increase patient’s safety. Conclusion: Although these agents have been marketed for five years (idarucizumab) and two years (andexanet alfa) respectively, and despite guidelines considering antidotes as first-line agents in treating life-threatening hemorrhage when available, these antidotes seem to gain access very slowly in the clinical practice. Cost, logistical aspects and need for plasma level determination of DOAC for an accurate therapeutic use probably have an impact on this phenomenon.. An expert multidisciplinary bleeding team should be established so as to implement international guidelines based on local resources and organization.

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A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Journal of Clinical Medicine ◽

10.3390/jcm10132924 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2924

Author(s):

Domenico Acanfora ◽

Marco Matteo Ciccone ◽

Valentina Carlomagno ◽

Pietro Scicchitano ◽

Chiara Acanfora ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Risk Index ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Efficacy Rate ◽

Cochrane Central Register ◽

Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

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Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.199 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

A Abdul Razzack ◽

N Hussain ◽

S Adeel Hassan ◽

S Mandava ◽

F Yasmin ◽

...

Keyword(s):

Molecular Weight ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Low Molecular Weight ◽

Efficacy And Safety ◽

Dichotomous Data ◽

Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and DOACs in the management of malignancy induced VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p < 0.05. Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p > 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

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Prescribing Errors With Direct Oral Anticoagulants and Their Impact on the Risk of Bleeding in Patients With Atrial Fibrillation

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/10742484211019657 ◽

2021 ◽

pp. 107424842110196

Author(s):

Bruria Hirsh Raccah, PharmD, PhD ◽

Yevgeni Erlichman ◽

Arthur Pollak ◽

Ilan Matok ◽

Mordechai Muszkat

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Negative Impact ◽

Conditional Logistic Regression ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Drug Dose ◽

Prescribing Errors ◽

Duration Of Treatment ◽

Inappropriate Treatment

Introduction: Anticoagulants are associated with significant harm when used in error, but there are limited data on potential harm of inappropriate treatment with direct oral anticoagulants (DOACs). We conducted a matched case-control study among atrial fibrillation (AF) patients admitting the hospital with a chronic treatment with DOACs, in order to assess factors associated with the risk of major bleeding. Methods: Patient data were documented using hospital’s computerized provider order entry system. Patients identified with major bleeding were defined as cases and were matched with controls based on the duration of treatment with DOACs and number of chronic medications. Appropriateness of prescribing was assessed based on the relevant clinical guidelines. Conditional logistic regression was used to evaluate the potential impact of safety-relevant prescribing errors with DOACs on major bleeding. Results: A total number of 509 eligible admissions were detected during the study period, including 64 cases of major bleeding and 445 controls. The prevalence of prescribing errors with DOACs was 33%. Most prevalent prescribing errors with DOACs were “drug dose too low” (16%) and “non-recommended combination of drugs” (11%). Safety-relevant prescribing errors with DOACs were associated with major bleeding [adjusted odds ratio (aOR) 2.17, 95% confidence interval (CI) 1.14-4.12]. Conclusion: Prescribers should be aware of the potential negative impact of prescribing errors with DOACs and understand the importance of proper prescribing and regular follow-up.

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Apixaban versus Warfarin in Patients with Left Ventricular (LV) Thrombus, a prospective randomized trial

European Heart Journal ◽

10.1093/ehjci/ehaa946.1545 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

R Alcalai ◽

R Rashad ◽

A Butnaru ◽

G Moravsky ◽

D Leibowitz

Keyword(s):

Major Bleeding ◽

Thrombus Formation ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Systemic Embolism ◽

Bleeding Events ◽

Open Label ◽

Warfarin Group ◽

Acute Mi

Abstract Background Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus. Aim To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Methods The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause. Results 25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment. Conclusions Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI. 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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