Management of oral anticoagulants prior to emergency surgery or with major bleeding: A survey of perioperative practices in North America: Communication from the Scientific and Standardization Committees on Perioperative and Critical Care Haemostasis and Thrombosis of the International Society on Thrombosis and Haemostasis

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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Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program

European Heart Journal ◽

10.1093/ehjci/ehaa946.0663 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Yamashita ◽

C.C Wang ◽

Y.-H Kim ◽

R De Caterina ◽

P Kirchhof ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Intracranial Haemorrhage ◽

Clinical Care ◽

Oral Anticoagulants ◽

Clinical Event ◽

Funding Source ◽

Private Company ◽

All Cause Mortality

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo

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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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Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.2396 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Tseng ◽

S Bhatt ◽

M Girardo ◽

D Liedl ◽

P Wennberg ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Triple Therapy ◽

Major Bleeding ◽

Antithrombotic Therapy ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Arterial Disease ◽

Risk Of Bleeding ◽

Increased Risk ◽

Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

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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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