Use Of DOACs Research Articles

Methods for detection of direct oral anticoagulants and their role in clinical practice

Introduction: Atrial fibrillation (AF) is the most common arrhythmia that increases by age, doubles for every decade after age of 50 years and reaches about 10% patients ≥ 80 years. Despite direct oral anticoagulants (DOACs’) predictable pharmacokinetics and pharmacodynamics, the laboratory tests are necessary for effective and safe medical treatment, also for prediction and detection of thrombotic and bleeding events, as well as in situations when temporary discontinuation could be desirable. Aim: of this study was to identify and analyze the need of coagulation tests for AF patients with high cardiovascular risk in clinical practice. Methods: Quantitative, analytic, cross-sectional clinical trial, during the period from October 2016 till June 2017, was performed at Pauls Stradins Clinical University Hospital, Center of Cardiology, Latvia. There were collected data about patients with non-valvular AF, under anticoagulative therapy ≥ 3 months, defined as a high-risk group by CHA2DS2 -VASc score-more or equal to 2 or 3, men and women respectively. Data were analyzed using SPSS. Results: There were collected data about 143 patients of whom 46.2% (n=66) were male; the mean age was 69.7 (SD ± 9.9) years. About 2/3 (73.1%) of all patients the AF were longer than 1 year. The mean CHA2DS2 -VASc score was 4.2 (SD ± 1.5). The most common comorbidies were arterial hypertension (65.0%; 93), chronic heart failure (48.3%; 69), coronary artery disease (32.9%; 47), diabetes mellitus (24.5%; 35), and dyslipidemia (25.9%; 37). Almost half of patients (46.2%; 66) used DOACs, 31.5% rivaroxaban and 14.7% dabigatran respectively; furthermore, 1.4% patients used DOACs’ with antiaggregants. 49.7% (71) patients had increased risk of possible drug-drug interactions, most frequently with proton pump inhibitors (16.8%; 24), amiodarone (24.5%; 35), antiinflammatory drugs (49.0%; 70). The use of DOACs and possible drug-drug interactions increases by risk score, reaching the maximum score 3 (16.1%; 23) and the mean frequent score 4.4 of 86 (60.1%) AF patients respectively. Conclusion: Coagulation tests were applicable more than half of patients (60.1%) to detect DOACs concentration in plasma. Despite DOACs’ expected pharmacokinetics and pharmacodynamics, the anticoagulant tests are necessary for effective and safe medical treatment, also for prediction and detection of thrombotic and bleeding events, as well as in situations when temporary discontinuation is desirable .

Direct oral anticoagulant– versus vitamin K antagonist–related gastrointestinal bleeding: Insights from a nationwide cohort

The purpose of the study was to examine the association between the type of preceding oral anticoagulant use (warfarin or direct oral anticoagulants [DOACs]) and in-hospital mortality among patients admitted with gastrointestinal bleeding. In this observational cohort study, all patients admitted with a first-time gastrointestinal bleeding from January 2011 to March 2017 while receiving any oral anticoagulant therapy prior to admission were identified using data from Danish nationwide registries. The risk of in-hospital mortality according to type of oral anticoagulation therapy was examined by multivariable logistic regression models. Among 5,774 patients admitted with gastrointestinal bleeding (median age, 78 years [25th-75th percentile, 71-85 years]; 56.8% men), 2,038 (35.3%) were receiving DOACs and 3,736 (64.7%) were receiving warfarin prior to admission. The unadjusted in-hospital mortality rates were 7.5% for DOAC (7.2% for dabigatran, 6.4% for rivaroxaban, and 10.1% for apixaban) and 6.5% for warfarin. After adjustment for baseline demographic and clinical characteristics, there was no statistically significant difference in in-hospital mortality between prior use of any DOAC and warfarin (unadjusted odds ratio [OR] 1.18 [95% CI 0.95-1.45], adjusted OR 0.97 [95% CI 0.77-1.24]). Similar results were found for each individual DOAC as compared with warfarin (dabigatran: unadjusted OR 1.12 [95% CI 0.84-1.49], adjusted OR 0.96 [95% CI 0.71-1.30]); rivaroxaban: unadjusted OR 0.98 [95% CI 0.71-1.37], adjusted OR 0.84 [95% CI 0.59-1.21]; and apixaban: unadjusted OR 1.62 [95% CI 0.84-1.49], adjusted OR 1.22 [95% CI 0.83-1.79]). Among patients admitted with gastrointestinal bleeding, there was no statistically significant difference in in-hospital mortality between prior use of DOAC and warfarin.

Vitamin K antagonist vs direct oral anticoagulants with antiplatelet therapy in dual or triple therapy after percutaneous coronary intervention or acute coronary syndrome in atrial fibrillation: Meta-analysis of randomized controlled trials.

BackgroundThe combination of vitamin K antagonists (VKA) for atrial fibrillation (AF) and antiplatelet agents following percutaneous coronary intervention (PCI) is associated with an increased bleeding risk.HypothesisDirect oral anticoagulants (DOAC) are associated with a greater safety profile but the optimal antithrombotic treatment strategy, especially when considering ischemic events, is unclear.MethodsWe performed a meta‐analysis of randomized controlled trials comparing outcomes in AF patients following PCI and/or acute coronary syndrome (ACS) when treated with DOAC vs VKA, both in combination with one (dual) or two (triple) antiplatelet regimens. A systematic review was performed by searches of electronic databases MEDLINE (source PubMed) and the Cochrane Controlled Clinical Trials Register Database as well as Cardiology annual meetings. Three studies were finally included.ResultsCompared to VKA triple therapy, the use of DOAC was associated with a decreased risk of any bleeding (relative risk [RR] 0.68 [0.62; 0.74]), major bleeding (RR 0.61 [0.51; 0.75]) and intracranial bleeding (RR 0.33 [0.17; 0.66]) and similar rates of the composite efficacy endpoint (RR 1.0 [0.87; 1.14]) and its components. Similar and consistent results were observed with both dual and triple therapy including a DOAC compared to VKA.ConclusionOur meta‐analysis supports the use of dual therapy combining a DOAC and clopidogrel as the default regimen in most AF patients after PCI and/or ACS.

Antithrombotic agents and traumatic brain injury in the elderly population: hemorrhage patterns and outcomes.

Among the elderly, use of antithrombotics (ATs), antiplatelets (APs; aspirin, clopidogrel), and/or anticoagulants (ACs; warfarin, direct oral ACs [DOACs; dabigatran, rivaroxaban, apixaban]) to prevent thromboembolic events must be carefully weighed against the risk of intracranial hemorrhage (ICH) with trauma. The goal of this study was to assess the risk of sustaining a traumatic brain injury (TBI), ICH, and poorer outcomes in relation to AT use among all patients 65 years or older presenting to a single institution with head trauma. Data were collected from all head trauma patients 65 years or older presenting to the authors' supraregional tertiary trauma center over a 24-month period and included age, sex, injury mechanism, medical history, international normalized ratio, Glasgow Coma Scale (GCS) score, ICH presence and type, hospital admission, reversal therapy, surgery, discharge destination, Extended Glasgow Outcome Scale (GOSE) score at discharge, and mortality. A total of 1365 head trauma patients 65 years or older were included; 724 were on AT therapy (413 on APs, 151 on ACs, 59 on DOACs, 48 on 2 APs, 38 on AP+AC, and 15 on AP+DOAC) and 641 were not. Among all head trauma patients, the risk of sustaining a TBI was associated with AP use after adjusting for covariates. Of the 731 TBI patients, those using ATs had higher rates of ICH (p <0.0001), functional dependency at discharge (GOSE score ≤ 4; p < 0.0001), and mortality (p < 0.0001). Elevated rates of ICH progression on follow-up CT scanning were observed in patients in the warfarin monotherapy (OR 5.30, p < 0.0001) and warfarin + AP (OR 6.15, p = 0.0011). Risk of mortality was not associated with single antiplatelet use but was notably high with 2 APs (OR 4.66, p = 0.0056), warfarin (OR 5.18, p = 0.0003), and DOAC use (OR 5.09, p = 0.0149). Elderly trauma patients on ATs, especially combination therapy, are at elevated risk of ICH and poor outcomes compared with those not on AT therapy. While both AP and warfarin use alone and in combination were associated with significantly elevated odds of sustaining an ICH among TBI patients, only warfarin use was a predictor of hemorrhage progression on follow-up scans. The use of a single AP was not associated with mortality; however, the combination of both aspirin and clopidogrel was. Warfarin and DOAC users had comparable mortality rates; however, DOAC users had lower rates of ICH progression, and fewer survivors were functionally dependent at discharge than were warfarin users. DOACs are an overall safer alternative to warfarin for patients at high risk of falls.

Safety of direct oral anticoagulants in patients with cirrhosis: a systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) are effective treatment for venous thromboembolism. However, safety data in patients with cirrhosis are limited. We conducted a systematic review and meta-analysis to evaluate the safety of DOACs compared with warfarin or low-molecular weight heparin in patients with cirrhosis. A systematic literature search was performed using MEDLINE and EMBASE from inception up to June 2018. We included prospective and retrospective studies involving adults ≥18 years with cirrhosis in whom anticoagulants were indicated for any indications. Primary outcome was all-cause bleeding events. Secondary outcome was major bleeding. Pooled risk ratio, pooled odd ratios and 95% confidence intervals (CIs) were calculated using random-effects model. Five studies with a total of 447 patients were included in the analysis. When compared with controls, the use of DOACs in cirrhotic patients did not show a significant difference in all-cause bleeding (risk ratio 0.72; 95% CI, 0.32-1.63). There was also no significant difference in major bleeding between both groups (odd ratio 0.46; 95% CI, 0.10-2.09). Our study demonstrates that, compared to those who were treated with traditional anticoagulants, cirrhotic patients who were treated with DOACs had no significant increase risk of all-cause bleeding and major bleeding.

Phenprocoumon based anticoagulation is an underestimated factor in the pathogenesis of calciphylaxis

BackgroundCalciphylaxis is a life threatening complication in renal patients. Of great importance is the identification of concomitant factors for calciphylaxis. Due to the variability of clinical presentation the evaluation of such factors may be obscured when calciphylaxis diagnosis is based just on clinical features. We aimed to characterize associated factors only in patients with calciphylaxis proven by histomorphological parameters in addition to clinical presentation.MethodsIn a single center retrospective study we analyzed 15 patients in an 8 year period from 2008 to 2016. Only patients with clinical features and histomorphological proof of calciphylaxis were included. Criteria for histological diagnosis of calciphylaxis were intimal hyperplasia, micro thrombi or von Kossa stain positive media calcification.ResultsThe mean age of patients was 64.8 years. Nine patients (60%) were female; 12 (80%) were obese with a Body-Mass-Index (BMI) > 30 kg/m2; 3 (20%) had no renal disease; 12 (80%) had CKD 4 or 5 and 10 (66.7%) had end-stage renal disease (ESRD). One-year mortality in the entire cohort was 73.3%.With respect to medication history, the majority of patients (n = 13 (86.7%)) received vitamin K antagonists (VKA); 10 (66.7%) were treated with vitamin D; 6 (40%) had oral calcium supplementation; 5 (33.3%) had been treated with corticosteroids; 12 (80%) were on proton pump inhibitors (PPI); 13 (86.7%) patients had a clinical proven hyperparathyroidism. Ten (66.7%) patients presented with hypoalbuminemia at diagnosis.ConclusionsThe evaluation of biopsy proven calciphylaxis demonstrates that especially treatment with vitamin K antagonists and liver dysfunction are most important concomitant factors in development of calciphylaxis. As progression and development of calciphylaxis are chronic rather than acute processes, early use of DOACs instead of VKA might be beneficial and reduce the incidence of calciphylaxis.

Effectiveness and Safety of Off-Label Dose-Reduced Direct Oral Anticoagulants in Atrial Fibrillation

BackgroundDirect oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment. MethodsThe study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression. ResultsA total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P < .001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008). ConclusionsAlmost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population.

Clinical and Radiological Characteristics of Vitamin K Versus Non-Vitamin K Antagonist Oral Anticoagulation-Related Intracerebral Hemorrhage

Recent studies indicated that functional outcome after intracranial hemorrhage (ICH) related to direct oral anticoagulation (DOAC-ICH) is similar, if not better, than vitamin K antagonist (VKA)-related ICH (VKA-ICH) due to a smaller initial hematoma volume (HV). However, the association with hematoma expansion (HE) and location is not well understood. We retrospectively analyzed 102 consecutive patients with acute non-traumatic ICH on oral anticoagulation therapy to determine HV and HE stratified by hematoma location, and the relation to the 90-day outcome. DOAC-ICH (n = 25) and VKA-ICH (n = 77) had a similar admission HV and HE (unadjusted p > 0.05, each). Targeted reversal strategies were used in 93.5% of VKA-ICH versus 8% of DOAC-ICH. After adjustment, an unfavorable 90-day functional outcome (modified Rankin scale score 4-6) was independently associated with alower admission Glasgow Coma Scale score (OR 1.63; 95% CI 1.26-2.10; p < 0.001) and greater HV (OR 1.03; 95% confidence interval (CI) 1.00-1.05; p = 0.046). After exclusion of patients without follow-up head computed tomography to allow for adjustment by occurrence of HE, VKA-ICH was associated with an approximately 3.5 times greater odds for a poor 90-day outcome (OR 3.64; 95% CI 1.01-13.09; p = 0.048). However, there was no significant association of the oral anticoagulant strategy with 90-day outcome in the entire cohort (OR 2.85; 95% CI 0.69-11.86; p = 0.15). DOAC use did not relate to worse HE, HV, and functional outcome after ICH, adding to the notion that DOAC is a safe alternative to VKA even in the absence of access to targeted reversal strategies (which are still not universally available).

Trends and Predictors of Oral Anticoagulation in Patients with Atrial Fibrillation: A Serial Cross-Sectional Study from 2011 to 2016

Abstract Background: Despite the efficacy of vitamin K antagonists against stroke in patients with atrial fibrillation (AF), the underuse of this therapy is well documented. Objectives: To evaluate trends and predictors of oral anticoagulants utilization in patients with AF. Methods: Observational, retrospective, serial cross-sectional study between 2011-2016. Comparisons between groups were performed using the Student t, Mann-Whitney and Chi-square tests. Logistic regression was used to identify independent predictors of anticoagulation. A p value < 0.05 was considered significant. Results: A total of 377 patients were analyzed. The mean age was 70 ± 15 years; 52% were male and 75% were anticoagulated (20% with VKA and 55% with DOAC). Over 5 years, the overall frequency of anticoagulation increased by 22.4%. The use of DOACs increased from 29% to 70%, whereas the use of VKA decreased from 36% to 17%. The use of antiplatelet agents alone also fell from 21% to 6%. The predictors of anticoagulation were previous episodes of AF (OR 3.1, p < 0.001), hypertension (OR 3.0, p < 0.001) and HASBLED score (OR 0.5, p < 0.001). The predictors of DOAC use were serum creatinine (OR 0.2, p = 0.002), left atrial size (OR 0.9, p = 0.003) and biological valve prosthesis (OR 0.1, p = 0.007). Of the 208 patients using DOACs, 63 (30%) received inadequate prescriptions: 5 with severe drug interactions and 58 with incorrect dosing. Conclusions: Between 2011 and 2016, DOACs were rapidly incorporated into clinical practice, replacing AVKs and antiplatelets, and contributing to greater use of anticoagulation in patients with AF.

Systematic literature review of treatment patterns for venous thromboembolism patients during transitions from inpatient to post-discharge settings.

IntroductionDirect oral anticoagulants (DOACs) have emerged as viable alternatives to traditional treatments such as vitamin K antagonists (VKAs) for venous thromboembolism (VTE). The objective of this review was to summarize evidence on the use of DOACs and VKAs to treat VTE in the US for patients transitioning from inpatient to post-discharge settings.Materials and methodsA systematic review of the VTE literature identified studies published in English (January 1, 2011–December 31, 2016) that reported inpatient and post-discharge treatments and discharge location. Two reviewers screened abstracts, abstracted information from included studies, and assessed the quality of the study methodology and reporting.ResultsForty-nine studies were included (24 clinical and 25 economic). A limited number of studies (eight clinical and three economic) examined VTE treatment patterns during transitions of care from inpatient to post-discharge settings, irrespective of anticoagulant (eg, DOAC, warfarin, heparin), and < 25% of all studies reported a post-discharge location. Three clinical studies that reported inpatient and outpatient treatment found better patient outcomes with DOAC vs warfarin. Fourteen economic studies reported that DOACs were associated with shorter hospital length of stay (LOS) and lower direct costs vs warfarin. No studies reported indirect costs.DiscussionAlthough DOACs are associated with shorter LOS, lower costs, and better patient outcomes vs VKAs, it appears in one study that only a small percentage of patients with stable VTE who are discharged to home may be receiving DOACs.ConclusionThese findings identified the potential areas of opportunity to improve the management of VTE through coordination of care from the inpatient to the outpatient settings.

Bleeding Management under Direct Oral Anticoagulants (DOAC)

Despite the widespread use of DOAC and recommendations of regulatory agencies and first consensus meetings on handling of bleeding situation under DOAC uncertainty still exists. In case of mild bleeding, the medical care of these patients and the delay of the next dose is advised. A laboratory analysis is indicated i. e. in case of known higher grade liver and kidney failure. The administration of factor concentrates or antidots is not indicated in this situation. In case of moderate to severe bleeding, the primary focus lies on stabilization of cardiopulmonary and circulatory function and parallel on the treatment depending on the localization of the bleeding source. In life-threatening bleeding in addition to the measures of hemodynamic stabilization a special haemostasis management may be required. In severe life-threatening bleeding treatment algorithms should be applied. In factor Xa-inhibitor-associated bleeding the use of factor concentrates (procoagulants), i. e. PCC in addition to unspecific measures, is indicated, as the direct antagonist andexanet alpha has not been approved in the EU. In contrast, the specific antagonist idarucizumab for acute dabigatran reversal is available in Germany.

Safety of urgent hip fracture surgery protocol under influence of direct oral anticoagulation medications

IntroductionDirect oral anticoagulation agents (DOACs) are increasingly prescribed to older adults. Concerns for perioperative blood loss dictate cessation of anticoagulation treatment and postponement of surgery until the coagulation system returns to normal state. The goal of this study is to compare the estimates of perioperative blood loss and mortality between patients using DOACs and patients receiving no anticoagultaion, in order to challenge the existing policy and question the need for surgery deferral. Materials and methodsThis is a retrospective cohort of patients (age > 65) with proximal hip fractures treated with either closed reduction internal fixation (CRIF, n = 1143; DOAC use n = 60) or hemiarthroplasty (HA, n = 571; DOAC use n = 29). Baseline patient characteristics included age, gender, ASA score, socioeconomic level, type of surgica#1: In general a l treatment, duration of surgery and time from admission to surgery. The effect of anticoagulant prescription on percentage of hemoglobin change, odds of receiving blood transfusions and one-month and one-year mortality was evaluated separately for CRIF and HA patients. ResultsPatients receiving DOACs had similar perioperative hemoglobin change, transfusion rates and mortality, compared to subjects without anticoagulants in both CRIF and HA cohorts. DOAC patients undergoing CRIF had a longer delay to surgery (40.2 ± 26.9 vs 31.2 ± 22.2, p = 0.003) and higher mortality rates at one year postoperatively (26.7% vs 16.1%, p = 0.015). ConclusionsDOAC use was not associated with an increased perioperative blood loss or mortality compared to controls. However, they had to wait longer for surgery, which itself was an independent predictor of mortality. It may be safe to shorten waiting time for surgery in patients using anticoagulation, with the goal to minimize surgery delay.

Current evidence of rivaroxaban in cancer-associated thrombosis

Patients with cancer have a high risk of developing cancer-associated thrombosis (CAT). Current guidelines suggest preferential use of low molecular weight heparins (LMWH) in CAT. The real-world data show that compliance with recommended LMWH therapy in cancer patients is low. Many patients discontinue injectable anticoagulants prematurely, in some cases even after a month, despite a high recurrence rate in this population. In recent years an increasing number of cancer patients are treated with direct oral anticoagulants, mainly rivaroxaban. Recent data confirming the safety and efficacy of rivaroxaban are starting to emerge and support the growing trend of using direct oral anticoagulants in cancer patients. If positive results of the recently completed SELECT-D trial are confirmed in the upcoming trials and registries of CALLISTO project, the guidelines for the treatment of CAT will have to be revised in favour of DOAC use in cancer-associated thrombosis.

Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review

IntroductionDirect oral anticoagulants (DOACs) are increasingly used for anticoagulation or prevention of thromboembolic events in conditions that may co-occur with pregnancy. However, evidence regarding efficacy and safety during pregnancy is scarce. AimTo review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans. MethodsWe systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017. Results236 cases of DOAC use during pregnancy were reported. Rivaroxaban was the most reported DOAC (n = 178). DOACs were mostly used for prophylaxis or treatment of venous thromboembolism (n = 91). DOACs were discontinued within the first 2 months of pregnancy in 84%, maximum reported duration of use was 26 weeks. Pregnancy outcome data were available for 140 pregnancies. Thirty-nine pregnancies were electively terminated. In the remaining 101 pregnancies total miscarriage rate was 31% (n = 31) and live birth rate was 68% (n = 69, 1 missing). Foetal and neonatal abnormalities were reported in 8 pregnancies, of which at least half were suspected to be related to rivaroxaban use during the 1st trimester of pregnancy. In only 18% of cases (n = 42), the presence or absence of thrombotic and bleeding complications was reported. ConclusionThe limited available evidence raises concern regarding embryo-foetal safety, with high incidence of miscarriages and a 4% rate of anomalies with the use of rivaroxaban. Not enough data are available to judge safety and efficacy of the use of DOACs during pregnancy.

Stroke prevention, 1-year clinical outcomes and healthcare resource utilization in patients with atrial fibrillation in France: Data from the GARFIELD-AF registry

GARFIELD-AF is a non-interventional worldwide study of adults with atrial fibrillation. To analyse the characteristics of the 1399 patients recruited in France from August 2010 to July 2015, their 1-year outcomes and healthcare resource utilization. Patients aged ≥18 years with newly diagnosed atrial fibrillation (≤6 weeks' duration) and ≥1 stroke risk factor were eligible. Patient demographics, medical history and antithrombotic treatment were recorded at baseline. The incidences of stroke/systemic embolism, major bleeding, all-cause mortality, cardiovascular and non-cardiovascular mortality, new acute coronary syndrome and congestive heart failure were recorded during a 1-year follow-up. The median age was 76.0 years; 44.5% of patients were female. The median CHA2DS2-VASc and HAS-BLED scores were 4.0 and 2.0, respectively. At diagnosis, 78.9% of patients received anticoagulant therapy±antiplatelet therapy; more patients received vitamin K antagonists (VKAs; 46.0%) than direct oral anticoagulants (DOACs; 32.9%). The median proportion of time in the therapeutic range for VKAs was 65.6%. Between 2010 and 2015, anticoagulant prescription increased, driven by the growing use of DOACs±antiplatelet therapy (1.1% to 50.0%), whereas prescription of VKAs±antiplatelet therapy decreased (74.4% to 32.3%). All-cause mortality was the most frequent event (6.75 per 100 person-years). Risk-adjusted event rates for France showed that stroke/systemic embolism and all-cause mortality occurred more frequently than in GARFIELD-AF overall, whereas the rates of major bleeding were similar. In terms of healthcare resource utilization, the highest cost was associated with inpatients. Patients enrolled in France had higher rates of mortality and stroke/systemic embolism than in GARFIELD-AF overall. Conversely, the risk of major bleeding was not higher.

DOAC use in patients with chronic kidney disease

SummaryDirect oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 286–294 https://doi.org/10.5482/HAMO-17-01-1657857

Pharmacy Student Monitoring of Direct Oral Anticoagulants

Background: Best practice recommendations are lacking. Thus far, literature has described pharmacist-led DOAC monitoring. Objective: The purpose of this study is to describe a DOAC monitoring program involving pharmacy students. Methods: This was an observational analysis of a quality improvement initiative. A clinical pharmacist preceptor identified clinic patients taking DOACs by running a report using the electronic medical record. Pharmacy students conducted chart reviews, called pharmacies for 6-month refill histories, and interviewed and educated patients. Findings were communicated to the care team and interventions were performed as applicable with the preceptor. Results: Of 90 patients included, the mean age was 63 years, 54% were female, and 65.6% were black or African American. Rivaroxaban and apixaban were used most commonly. Sixty-two percent of DOACs were prescribed for atrial fibrillation/flutter, while 32.2% for venous thromboembolism. The mean MPR was 77.1%, with 27.7% of patients having an MPR ≤60%. Of the 136 student-led interventions, 25.2% involved medication access, 24.4% adherence education, 20.7% processing refills, 14.8% laboratory monitoring recommendations, 8.9% switching or recommending switching to another anticoagulant, and 4.4% stopping a nonsteroidal anti-inflammatory drug or aspirin. Conclusion: Pharmacy students can help to ensure medication safety and effective use of DOACs.

Management of cancer-associated venous thromboembolism – a case-based practical approach

In patients with solid tumours or haematological malignancies, venous thromboembolism (VTE) is a leading cause of death and significantly contributes to morbidity and healthcare resource utilization. Current practice guidelines recommend long-term anticoagulation with low-molecular-weight heparin (LMWH) as the treatment of choice for cancer-associated VTE, based on clinical trial data showing an overall improved safety and efficacy profile of LMWH compared to vitamin K antagonists. However, several open questions remain, e. g. with regard to the intensity and duration of LMWH therapy; moreover, recent real-world evidence indicates that adherence to parenteral anticoagulation with LMWH over the course of treatment is poor in clinical practice. In this regard, the direct oral factor Xa or thrombin inhibitors (DOACs) have emerged as potential alternatives in the management of patients with cancer-associated VTE, albeit findings from randomized controlled studies with a direct head-to-head comparison of DOACs with LMWH, the current standard of care, are still lacking. Based on the case of a lymphoma patient experiencing symptomatic pulmonary embolism during immunochemotherapy, this article aims at both highlighting the current state-of-the-art approach to cancer-associated VTE and pointing out some of the unresolved, controversial issues clinicians have to face when taking care of haematology and oncology patients with already established or with high risk of developing VTE. These issues include the management of patients with incidental pulmonary embolism or thrombocytopenia, the use of DOACs, and the initiation of pharmacological thromboprophylaxis in non-surgical cancer patients.

Methods for Detection of Direct Oral Anticoagulants and their Role in Clinical Practice

Introduction: Atrial fibrillation (AF) is the most common arrhythmia that increases by age, doubles for every decade after age of 50 years and reaches about 10% patients ≥ 80 years. Despite direct oral anticoagulants (DOACs’) predictable pharmacokinetics and pharmacodynamics, the laboratory tests are necessary for effective and safe medical treatment, also for prediction and detection of thrombotic and bleeding events, as well as in situations when temporary discontinuation could be desirable. Aim: of this study was to identify and analyze the need of coagulation tests for AF patients with high cardiovascular risk in clinical practice. Methods: Quantitative, analytic, cross-sectional clinical trial, during the period from October 2016 till June 2017, was performed at Pauls Stradins Clinical University Hospital, Center of Cardiology, Latvia. There were collected data about patients with non-valvular AF, under anticoagulative therapy ≥ 3 months, defined as a high-risk group by CHA2DS2 -VASc score-more or equal to 2 or 3, men and women respectively. Data were analyzed using SPSS. Results: There were collected data about 143 patients of whom 46.2% (n=66) were male; the mean age was 69.7 (SD ± 9.9) years. About 2/3 (73.1%) of all patients the AF were longer than 1 year. The mean CHA2DS2 -VASc score was 4.2 (SD ± 1.5). The most common comorbidies were arterial hypertension (65.0%; 93), chronic heart failure (48.3%; 69), coronary artery disease (32.9%; 47), diabetes mellitus (24.5%; 35), and dyslipidemia (25.9%; 37). Almost half of patients (46.2%; 66) used DOACs, 31.5% rivaroxaban and 14.7% dabigatran respectively; furthermore, 1.4% patients used DOACs’ with antiaggregants. 49.7% (71) patients had increased risk of possible drug-drug interactions, most frequently with proton pump inhibitors (16.8%; 24), amiodarone (24.5%; 35), antiinflammatory drugs (49.0%; 70). The use of DOACs and possible drug-drug interactions increases by risk score, reaching the maximum score 3 (16.1%; 23) and the mean frequent score 4.4 of 86 (60.1%) AF patients respectively. Conclusion: Coagulation tests were applicable more than half of patients (60.1%) to detect DOACs concentration in plasma. Despite DOACs’ expected pharmacokinetics and pharmacodynamics, the anticoagulant tests are necessary for effective and safe medical treatment, also for prediction and detection of thrombotic and bleeding events, as well as in situations when temporary discontinuation is desirable .

Efficacy and Safety Outcomes of Direct Oral Anticoagulants and Amiodarone in Patients with Atrial Fibrillation

BackgroundDirect oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of nonvalvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. Direct oral anticoagulant levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors, such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug–drug interaction by the concomitant use of DOACs and amiodarone. MethodsWe performed a systematic review of MEDLINE, the Cochrane Central Register of Clinical Trials, and Embase, limiting our search to randomized controlled trials of patients with atrial fibrillation that have compared DOACs versus warfarin for prophylaxis of stroke or systemic embolism, to analyze the impact on stroke or systemic embolism, major bleeding, and intracranial bleeding risk in patients with concomitant use of amiodarone. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The fixed effects model was used owing to heterogeneity (I2) < 25%. ResultsFour trials with a total of 71,683 patients were analyzed, from which 5% of patients (n = 3212) were concomitantly taking DOAC and amiodarone. We found no statistically significant difference for any of the clinical outcomes (stroke or systemic embolism [RR 0.85; 95% CI, 0.67-1.06], major bleeding [RR 0.91; 95% CI, 0.77-1.07], or intracranial bleeding [RR 1.10; 95% CI, 0.68-1.78]) among patients taking DOAC and amiodarone versus DOAC without amiodarone. ConclusionOn the basis of the results of this meta-analysis, co-administration of DOACs and amiodarone, a dual P-gp/CYP3A4 inhibitor, does not seem to affect efficacy or safety outcomes in patients with atrial fibrillation.