New Oral Anticoagulants Research Articles

Critical Issues and Recent Advances in Anticoagulant Therapy: A Review.

As the population is aging, clinicians are coming across more patients with atrial fibrillation and venous thromboembolism requiring anticoagulation to prevent stroke and systemic embolisms. Due to a high prevalence and unfavorable consequences, managing thromboembolic diseases have become areas of clinical concern. Traditional anticoagulants like heparin, low molecular weight heparin and warfarin have been used for the prevention and treatment of venous and arterial thromboses. But, issues of bleeding, parenteral route of administration, or the need for frequent monitoring due to variability in response respectively limit their use. The article gives an overview of coagulation along with existing therapy available for anticoagulation and to present an update on utility and recent advances of new oral anticoagulants (NOACs) beginning from their nomenclature, advantages, disadvantages, precautions and contraindications compared with those of vitamin K antagonists (VKAs) based on a large number of recent studies and clinical trials.

Effect of ABCB1 Genotypes on the Pharmacokinetics and Clinical Outcomes of New Oral Anticoagulants: A Systematic Review and Meta-analysis.

New Oral Anticoagulants (NOACs) are effective and widely used to prevent and treat thromboembolic diseases, but the response to NOACs differs according to ABCB1 genotypes. We investigated the effects of ABCB1 genotypes on the pharmacokinetics and clinical outcomes of NOACs. We searched PubMed, Embase, and the Cochrane Library for studies on ABCB1 genotypes published from the inception of these databases until May 23, 2018. The Weighted Mean Difference (WMD) and Odds Ratio (OR) with 95% Confidence Interval (CI) were calculated for continuous and dichotomous data, respectively. Summary results were calculated using a random effects model. Ten studies involving 2609 individuals were included in the systematic review, and three studies involving 535 individuals were included in the meta-analysis. Overall, four ABCB1 single-nucleotide polymorphisms were identified in the review. Carriers of the ABCB1 rs1045642 CC genotype had lower maximum plasma concentration (Cmax) than those of TT (WMD = -16.99 ng/mL; 95% CI = -33.39 to -0.59; P = 0.04), and carriers of the rs2032582 GG genotype showed lower Cmax than those of the A/T allele (WMD = -19.21 ng/mL; 95% CI = -36.62 to -1.80; P = 0.03). Carriers of the rs1045642 CC genotype showed lower area under the curve from time 0 to infinity (AUC0-∞) than those of the T allele (WMD = -78.58 ng·h/mL; 95% CI = -151.14 to -6.01; P = 0.03). ABCB1 rs4148738 genotypes did not affect the risks of ischemic stroke or systemic embolism (OR = 0.88), ischemic events (OR = 0.98), bleeding (OR = 0.94), major bleeding (OR = 1.14), or minor bleeding (OR = 0.94) in patients treated with dabigatran. Cmax was lower in carriers of ABCB1 rs1045642 CC than in those of TT and in carriers of rs2032582 GG than in those of the A/T allele, and AUC0-∞ was lower in carriers of rs1045642 CC than in those of TT. Conversely, ABCB1 rs4148738 genotypes did not affect primary clinical endpoints in dabigatran-administered patients. Future studies should analyze the relationships of ABCB1 genotypes with the pharmacokinetics and clinical outcomes of specific NOACs.

Oral anticoagulant therapy in a patient with CHA₂DS₂-VASc score 1

Controlled studies of new oral anticoagulants (NOACs) in patients with atrial fibrillation have included above all patients at high risk of stroke, providing solid evidence on the benefits of anticoagulant therapy with such drugs in male patients with CHA2DS2-VASc score ≥2 and in women with a score of ≥3. Although estimates of stroke risk in patients with lower scores predominantly come from studies in patients not receiving NOAC, in many of these subjects anticoagulant therapy still seems able to provide clinical benefit. The current guidelines therefore recommend oral anticoagulant therapy in patients with CHA2DS2-VASc ≥1 in men and ≥2 in women. However, the use of this therapy must be carefully weighted with the expected reduction in the risk of stroke, the risk of bleeding and the patient's preferences. The paradygmatic case of a patient with CHA2DS2-VASc score 1 is reported in which acetylsalicylic acid therapy is substituted with dabigatran 150 mg / day in order to guarantee the patient maximum protection against the risk of stroke, without exposing him to an excessive risk of bleeding (Cardiology).

Dabigatran in the ischemic patient undergoing atrial fibrillation ablation

Trans-catheter ablation of atrial fibrillation (AF) is a common treatment for symptomatic AF. Among the major complications of AF ablation are stroke, transient ischemic attacks and peri-procedural cardiac tamponade. Various clinical trials have shown that uninterrupted treatment with vitamin K antagonists (VKA) is associated with a lower incidence of embolic events compared to discontinuation of therapy; until recently, in the absence of equally solid evidence, this practice was not extended to the new oral anticoagulants (NOAC) not VKA due to the fear of hemorrhagic complications potentially associated with the use of an "irreversible" anticoagulant. The case of a patient suffering from numerous comorbidities is reported here. In light of the poor response to anti-arrhythmics, a TC-RF ablation was performed, with suspension of dabigatran administration only on the day of the procedure (for a total period <24 hours). Although the fear of the risk of bleeding potentially associated with the trans-catheter ablation procedure may still induce clinicians to stop anticoagulant therapy, even the decision to discontinue anticoagulant therapy with dabigatran on the day of surgery alone is challenged by recent evidence in the literature supporting the efficacy of dabigatran in reducing the incidence of hemorrhagic events during and after ablation, including the results of the RE-CIRCUIT study (Cardiology)

Predictors of new oral anticoagulant drug initiation as opposed to warfarin in elderly adults: a retrospective observational study in Southern Italy.

AimThe aim of this study was to assess the predictive role of age, gender, and number and type of co-treatments for new oral anticoagulant (NOAC) vs warfarin prescription in elderly patients naïve for the aforementioned drugs.Materials and methodsData collected in the period from January 1, 2014, to December 31, 2014, in Caserta Local Health Unit administrative databases (Campania Region, Italy) were screened to identify new users of oral anticoagulants (OACs) who were 75 years or older and whose OAC prescriptions amounted to >90 days of treatment. Age, gender, and number and type of concomitant medications at the time of first OAC dispensation were retrieved. Multivariable logistic regression analysis was used to assess the role of the aforementioned predictors for NOAC initiation as opposed to warfarin.ResultsOverall, 2,132 incident users of OAC were identified, of whom 967 met all inclusion criteria. In all, 490 subjects (50.7%) received an NOAC and 477 (49.3%) received warfarin. Age >75 years was positively associated with lower odds of NOAC initiation (OR: 0.969, 95% CI: 0.941–0.998, P=0.038). Similarly, multiple concomitant medication was negatively associated with NOAC initiation compared to warfarin (OR [five to nine drugs] group: 0.607, 95% CI: 0.432–0.852, P=0.004; OR [ten+ drugs] group: 0.372, 95% CI: 0.244–0.567, P<0.001). Prior exposure to platelet aggregation inhibitor drugs was associated with the initiation of NOACs (OR: 3.474, 95% CI: 2.610–4.625).ConclusionAge and multiple co-medication were negatively associated with NOAC initiation.

Clinical analysis of antithrombotic treatment and occurrence of stroke in elderly patients with nonvalvular persistent atrial fibrillation.

Atrial fibrillation (AF) is common in elderly patients and is associated with ischemic stroke. We sought to explore the current status of antithrombotic therapy in elderly patients with nonvalvular persistent AF. This is a retrospective study and data were collected from the First Hospital of China Medical University. A total of 300 patients were enrolled from January 2015 to June 2017. Patients were divided into two groups: Group 1 (from 65-74) and Group 2 (older than 75). The status of antithrombotic treatment was recorded. Follow-ups were done at 7, 90 , 180, and 360 days after discharge. The occurrence of stroke was recorded. For 287 patients with a CHA2 DS2 -VASc score ≥2, 41.10% received oral anticoagulants (OAC), 27.20% received new oral anticoagulants (NOAC), 42.20% received antiplatelet agents, 16.70% received no antithrombotic treatment. From 2015 to the first half 2017, the ratio of OAC was 25.90%, 51.89%, and 49.30%, respectively; ratio of NOAC were 16.90%, 30.19%, and 39.10%, respectively. During the four times follow-up, percentage of patients who had good treatment compliance was 65%, 49.2%, 38.5%, and 25% stroke rate was 6.7% in total 300 patients. Logistic regression analysis showed age older than 75 (odds ratio [OR] 4.812), prior stroke (OR 4.109) were risk factors of stroke, and OAC treatment (OR 0.021) could prevent stroke. Ratio of antithrombotic therapy in elderly patients with nonvalvular persistent AF was low and drug compliance was poor. Age, prior history of stroke, and OAC treatment are the important predictive factors of stoke in elderly patients.

AN EVALUATION OF THE SAFETY OF NEW ORAL ANTICOAGULANTS FOLLOWING CARDIAC SURGERY

The new oral anticoagulants (NOACs) have become an easier and more practical alternative to Warfarin because of the absence of monitoring needed due to their more stable effect over a short period of time, as it’s often needed after cardiac surgery. The aim of this study was to determine the safety of the NOACs in the first three months following cardiac surgery. Between January 2012 and June 2017, 207 patients received NOACs following their cardiac surgery in our center. Patient’s files were reviewed retrospectively. Demographic and perioperative data were collected. Complications that may arise in the first three months post-operatively due to NOACs use were noted. Among the 207 patients studied, 72 % (n=149) were men and the mean age was 70.8 ±1.3 years. As much as 36.7% (n=76) underwent a coronary artery bypass graft (CABG), 38.6% (n=80) had a valve replacement or repair, 22.2% (n=46) underwent both a CABG and a valve replacement and only 2.4% (n=5) had a replacement of the ascending aorta. Ten percent (n=21) were lost to follow-up with an average follow-up period of 7.3 ±1 months. In total, 18 patients (8%) have suffered complications possibly due to the NOAC, but only three (1%) suffered hemorrhagic complications. Among these, only one patient needed transfusions. For the rest, 15 (7%) suffered non-hemorrhagic complications: pleural effusions (n=10), pericardial effusion (n=3), both pleural and pericardial effusions (n=1), thromboembolic event (n=1). Patients received Apixaban, Rivaroxaban or Dabigatran, but the majority were taking Apixaban (n=171, 82.6%). We cannot draw a conclusion as to which NOAC is safest due to the very small number of patients receiving Rivaroxaban and Dabigatran. Finally, 33.3% (n=6) of the complications arose in the first month after the surgery, 38.9% (n=7) in the second month, 16.7% (n=3) in the third month and 11.1% (n=2) after more than 3 months. Based on the results of a previous study done in our center, comparing Warfarin and NOAC, there is no significant difference between the number of complications possibly due to NOAC and those possibly caused by Warfarin. Therefore, NOACs are deemed a safe option after cardiac surgery. A randomized clinical trial would be needed to confirm our findings.

Hepatotoxicity of New Oral Anticoagulants

Aim. To summarize and systematize the information published in open sources on the development of various manifestations of liver damage in the use of the new oral anticoagulants (NOAC) for the registered indications and to analyze the published clinical cases of drug induced liver injury (DILI) development. Material and methods. Search queries for keywords were made in the PubMed (MEDLINE), Scopus, Elibrary and Kiberleninka databases. The search query was composed of the name of the medicinal product (international non-proprietary and commercial name) or the common name of the group and words describing the different variants of the liver damage. Results. As a result of the search 1497 articles were found. Duplicate articles, articles that do not match the review topic, and articles whose full-text version is not available were removed from the search results. Articles that do not describe specific clinical cases have also been excluded. The review includes 14 articles, published from 2007 to March 2018 in Russian and English and one article in French describing clinical cases of different types of hepatotoxicity in the application of NOAC. Conclusions. Published clinical cases suggest that NOAC cause undesirable phenomena such as hepatotoxicity, the mechanism and frequency of which remain unclear.

Catheter-based atrial appendage closure-current data and future developments

In Germany more than 1.6 million patients suffer from atrial fibrillation (AF). Within the next decades this number will substantially increase due to current demographic trends with the increasing average age of the population. When untreated, patients with atrial fibrillation have afive times higher risk for stroke as compared with acontrol cohort. Apotent stroke prevention therapy reducing the risk of stroke by approximately 70-80% is primarily treatment with new oral anticoagulants (NOACs). The risk scores for stroke (CHA2DS2-VASc) and major bleeding (HAS-BLED) in patients with atrial fibrillation share common variables, so that patients with the highest stroke risk often carry avery high bleeding risk. Asignificant number of patients (ca.20-30%) are, however, not eligible for long-term anticoagulation, e.g. because of ahigh bleeding risk. For this population there is an urgent need for alternative stroke prevention strategies, such as catheter-based percutaneous left atrial appendage closure. Current data about the efficiency and safety of this treatment as well as adiscussion of ongoing recruitment for randomized studies are discussed in this review.

The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis.

New oral anticoagulants (NOACs; ie, direct thrombin inhibitor [DTI] and factor Xa [FXa] inhibitors) were used as alternatives to warfarin. Specific antidotes (idarucizumab for dabigatran and andexanet alfa for FXa inhibitors) and hemostatic reversal agents were used for lowering bleeding, but their efficacies were still uncertain. The objectives of this study were to estimate and compare the efficacy of NOAC antidotes on bleeding reversal and death. Studies were identified from MEDLINE and Scopus databases until May 2018. Case reports/series and cohorts were selected if they assessed reversal or death rates. Data were independently extracted by 2 reviewers. Individual patient data and aggregated data of outcomes were extracted from case reports/series and cohorts. Binary regression was used to estimate outcome rates, risk ratio (RR) along with 95% confidence interval (CI). Interventions were NOACs and reversal agents (ie, DTI-specific, DTI-standard, FXa-specific, and FXa-standard). Among 220 patients of 93 case reports/series, reversal rates were 95.9%, 77.6%, and 71.5% for DTI-specific, FXa-standard, and DTI-standard. Pooled RRs for DTI-specific and FXa-standard versus DTI-standard, respectively, were 1.34 (CI: 1.13-1.60) and 1.09 (CI: 0.84-1.40). Death rate was 0.18 (CI: 0.06-0.57) times lower in DTI-specific versus DTI-standard. For pooling 10 subcohorts, pooled RRs were 1.08 (CI: 1.00-1.16), 1.29 (CI: 1.20-1.39), and 1.13 (CI: 1.01-1.25) for DTI-specific, FXa-specific, and FXa-standard versus DTI-standard. In conclusion, specific reversal agents might be useful for reversal of bleeding and lowering the risk of death than standard reversal agents. Our findings were based on case reports/series and selected cohorts, further comparative studies are thus needed.

Atrial Fibrillation a Benign Condition? Quality of Life Approach

Abstract Introduction: Atrial fibrillation (AF) is the most frequent cardiac rhythm disorder, considered until recently benign. Due to its major complications (cardio-embolic episodes) patients need to be anticoagulated. Aim: To assess the quality of life (QOL) in patients with new oral anticoagulants (NOAC) versus those using classical anticoagulants (VKA). Methods: A total of 483 patients admitted consecutively in our clinic were evaluated during hospitalization and after discharge. Follow-up visits were conducted: at baseline, 6, 12, 18 and 24 months; the quality of life (QoL) was measured by a specific questionnaire (EQ-5D-3L), and the results were assessed. Patients were divided in two groups considering their anticoagulant use: NOAC or VKA. Baseline characteristics, clinical outcomes as well as QoL indices were compared between the two groups The current research has been conducted in accordance with the ethical prin ciples set out in the Helsinki Declaration and Good Clinical Practice Recommendations and was approved by our hospital Ethics Committee. Results: The mean age of our studied group (374 eligible patients) was 64.7 ± 8.2 years (p=0.220); 116 patients (31.01%) used NOAC. Patients with NOAC obtained better results in all domains: physical (57.0±8.9 vs. 51.1±12.5 vs. 42.0±6.2; p&lt;0.001), social (62.6±19.8 vs. 52.5±20.0 vs. 45.7±16.0; p=0.019) and environmental (62.9±12.7 vs. 52.7±7.6 vs. 60.7±3.6; p =0.018). Compared to VKAs, NOACs were more commonly prescribed in patients with a history of stroke or with a higher thromboembolic risk (p&lt;0.001). EQ-5D-3L total score: 75.6 ± 20.9; visual analogue scale: 63.1 ± 20.6. Conclusion(s): Satisfaction and QoL with oral anticoagulants were high, although they were both better with NOACs. A worse QoL was associated with comorbidities, polypragmasy, and previous treatment with VKA. Patients strongly expressed their desire to improve their QoL.

Venous thromboembolism - update 2019

Venous thromboembolism - update 2019 Abstract. Abstract:The implication of new diagnostic algorithms in our daily clinical routine has simplified the diagnostic certainty, particularly in the case of exclusion of venous thromboembolism (VTE), so that even the general practitioner can already rule out venous thromboembolism with sufficient certainty. The introduction of risk scores in patients with a confirmed diagnosis can help to identify those patients who are at particular risk so you can monitor them. On the other hand, outpatient treatment of patients with pulmonary embolism in the low-risk category increases significantly. With the introduction of the new oral anticoagulants (NOAC), the treatment of these patients has been significantly simplified, and the risk of major bleeding compared to the vitamin K antagonists has been significantly reduced. For patients with paraneoplastic VTEs, the NOACs will also be an option in the future, which must be validated in studies even more precisely. Due to the low risk of bleeding NOACs in prophylactic dosing, the proportion of patients undergoing extended secondary prophylaxis will continue to increase in the future, reducing the risk of VTE recurrence.

Worsening head bleeds in elderly blunt head trauma patients taking antithrombotics: Delayed CT head fails to change management

BackgroundMost elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population. MethodsA retrospective cohort study was performed. Patients ≥65 years sustaining blunt head injuries from January 2010 to July 2017 were identified using our level 1 trauma center database. AT-patients presenting with ICH who underwent D-CTH were included. Patients with worsened ICH were compared to those with stable to improved ICH on D-CTH. AT-patients were compared to a cohort of non-AT patients. Fisher’s Exact and Mann-Whitney U tests were utilized and a power analysis conducted. Results137 A T and 34 non-AT patients were identified. There was no difference in hemorrhage progression or appearance of new ICH. No patient had a change in management from D-CTH in either cohort. AT-patients were slightly older (p < 0.001), but cohorts were otherwise similar.50 AT-patients with worsened ICH were compared to 87 with stable ICH. There was no difference in cohort demographics. Hemorrhage progression did not vary with type of AT used but did increase if multiple types of synchronous ICH were present (p < 0.001). ConclusionsOur data supports abstaining from routine D-CTH of elderly ICH patients with an intact neurologic examination who are utilizing aspirin, clopidogrel or warfarin. Conclusions cannot be drawn regarding new oral anticoagulants (NOACs) given low enrollment. Further multicenter study is required to provide adequate power and detect small levels of management change.

APPROACHES TO THE CHOICE OF ANTICOAGULANT THERAPY IN THE TREATMENT OF PATIENTS WITH COMBINATION OF ATRIAL FIBRILLATION WITH CORONARY HEART DISEASE OR PERIPHERAL ATHEROSCLEROSIS: POTENTIAL OF APIXABAN

The choice of anticoagulant therapy in patients with atrial fibrillation (AF) and concomitant diseases – coronary heart disease (CHD), including acute coronary syndrome (ACS) in history, peripheral arterial disease (PAD), is discussed in the article. The overall mortality and incidence of myocardial infarction in patients with CHD and AF is higher than in patients with AF without CHD. Patients with AF and PAD compared to patients with AF without PAD have higher risks both stroke and systemic embolism. The prescription of triple antithrombotic therapy is necessary for patients with a combination of AF and CHD who underwent percutaneous coronary interventions (in ACS or elective surgery). The possibility of prescription and duration, the choice of specific drugs and their doses should be determined individually, based on the risks of ischemic events associated with stenting, the risk of ischemic stroke and bleeding. Use of new oral anticoagulants (NOAC) instead of vitamin K antagonists (eg, warfarin), low doses of NOAC, studied in trials and proven efficacy in the prevention of stroke/systemic embolism, the use of clopidogrel as a drug of choice from the P2Y12 inhibitor group, the use of low doses of acetylsalicylic acid (ASA), the routine administration of drugs from the proton pump inhibitor group is recommended to minimize the risk of bleeding. The data of subanalysis of the ARISTOTEL randomized clinical trial, indicating a high profile of efficacy and safety of apixaban in patients with AF, depending on the presence of CHD, PAD, concomitant use of ASA, are also presented in the article. The benefits of apixaban over warfarin for reducing the risk of stroke/systemic embolism, total mortality and the risk of bleeding in a subgroup of CHD patients are just as obvious as in the general population of the ARISTOTLE study, and in the subgroup of patients without CHD. Treatment with apixaban, both in the subgroup of patients taking ASA, and a subgroup of patients without ASA, is accompanied by a lower risk of strokes and systemic embolism and a lower incidence of major bleeding. The risk of stroke or systemic embolism was similar in patients with AF and PAD randomized to the apixaban group or to the warfarin group, as well as in patients with AF without PAD. Patients with AF and PAD who received apixaban or warfarin had a similar incidence of major bleeding or clinically significant minor bleeding.

NOAC in "real world" patients with atrial fibrillation in Italy: results from the ISPAF-2 (Indagine Sicoa Paziente Con Fibrillazione Atriale) survey study.

In the past few years, new oral anticoagulants (NOACs) targeting directly a single activated clotting factor, have been developed for the treatment of non-valvular atrial fibrillation (AF), which are currently recommended as first-line therapy in AF. The aim of this study is to provide an overall picture on the extent to which oral anticoagulation (OAC) with NOACs correspond to actually prescribed OAC therapy in an unselected, real world, population of consecutive patients with AF in Italy. Compliance with the therapy and quality of life were also assessed. A 50 cardiology unit network located in different geographic areas of Italy enrolled a total of 1742 consecutive outpatients with AF (54.6% males, 45.4% females, mean age 72.5years). NOACs were prescribed in 56.1% patients and VKA in 43.9% (P < 0.0001). NOACs were significantly more prescribed than VKA in patients with high thrombo-embolic risk score (i.e., CHA2DS2-VASc > 2) (78.2 vs 67.3%, P < 0.0001), but also patients at low risk (i.e., CHA2DS2-VASc < 1 and HAS-BLED < 3) were still under OAC therapy with either NOACs (27%) or VKA (73%). Adherence to therapy (Morisky test) was greater in patients taking NOACs as was the quality of life. The ISPAF-2 study shows that in an Italian population of real-world patients with AF the prescription of OAC according to current guidelines and stroke-risk scoring system is rather high although it still needs to be improved. Contrary to recommendations, in a high proportion of low-risk patients, anticoagulation therapy, with either NOACs and VKA is still prescribed, and this exposes patients to unjustified risks.

Newer Oral Anticoagulants in the Treatment of Acute Portal Vein Thrombosis in Patients with and without Cirrhosis.

Background Newer oral anticoagulants (NOACs) are being utilized increasingly for the treatment of venous thromboembolism (VTE). NOAC use is the standard of care for stroke prophylaxis in nonvalvular atrial fibrillation and treatment of acute VTE involving extremities and pulmonary embolism. In contrast, most guidelines in the literature support the treatment of acute portal vein thrombosis (PVT) with low molecular weight heparin (LMWH) and vitamin K antagonists (VKA). Literature evaluating NOAC use in the treatment of acute portal vein thrombosis is sparse. This review focuses on the safety and efficacy of the use of NOACs in the treatment of acute PVT in patients, with or without concomitant cirrhosis, based on the most recent data available in the current literature. Methods A systematic review was conducted through a series of advanced searches in the following medical databases: PubMed, BioMed Central, Cochrane, and Google Scholar. Keywords utilized were as follows: NOAC, DOAC (direct oral anticoagulants), portal vein thrombosis, rivaroxaban, apixaban, dabigatran, and edoxaban. Articles related to newer anticoagulant use in patients with portal vein thrombosis were included. Results The adverse events, including bleeding events (major and minor) and the failure of anticoagulation (propagation of thrombus or recurrence of PVT), are similar between the NOACs and traditional anticoagulants for the treatment of acute PVT, irrespective of the presence of cirrhosis. Conclusions Newer oral anticoagulants are safe and efficacious alternatives to traditional anticoagulation with low molecular weight heparin and vitamin K antagonists in the treatment of acute portal vein thrombosis with or without cirrhosis.

Clinical Challenges of Using Novel Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent arrhythmia, and patients with AF have an increased risk of stroke. According to the CHA2DS2-VASc scoring system, stroke risk is greater when these patients are older than 65 years; are female; have systolic heart failure, diabetes mellitus, hypertension, peripheral vascular disease, or a recent myocardial infarction; or have a history of stroke or transient ischemic attack.1 Oral anticoagulants are the mainstay therapy for stroke prevention in AF patients. Drugs called new oral anticoagulants (NOACs) are often prescribed for this purpose and are as effective as warfarin. Currently, 4 NOACs are approved by the U.S. Food and Drug Administration: dabigatran (a direct thrombin inhibitor), rivaroxaban, apixaban, and edoxaban (a direct factor Xa inhibitor). Only dabigatran has a reversal agent. In comparison with warfarin, NOACs have fewer interactions with foods and medications, and routine bloodwork is not required to evaluate patients' anticoagulation levels when they take these drugs.1–3When NOACs are prescribed instead of warfarin, considerations include patients' renal and liver function, and possible drug interactions. A management challenge is to formulate an appropriate plan for NOAC use before noncardiac surgery, with answers to the following questions: should we hold NOACs? When should they be stopped? Do we need to bridge the patient with heparin? When should we restart the NOACs? Other factors to consider are the risk of bleeding associated with the procedure, the patient's individual risk of stroke and bleeding, and the type of NOAC to use.2 Bridging is not typically recommended for NOACs.2 For example, in a patient with persistent AF who is taking apixaban, has a CHA2DS2-VASc score of 3, has normal renal function, and is to undergo transurethral resection of the prostate (associated with a high risk of bleeding), apixaban should be stopped 48 hours preoperatively, without heparin bridging; it can be restarted as soon as the surgeon determines that doing so is safe.Cytochrome P450 subgroup CYP3A4 is important in the metabolism of NOACs,4 P-glycoprotein in their absorption, and renal function in their excretion. Medications that induce or inhibit the functions of CYP3A4 or P-glycoprotein can affect the bioavailability of NOACs and increase the risk of bleeding or thromboembolism.4 One such, an over-the-counter supplement, is St. John's wort. Typically taken as therapy for psychological depression, this herb induces P-glycoprotein and can thus decrease the bioavailability of dabigatran.Therapy with NOACs is limited in patients with valvular heart disease. However, current data suggest that NOACs can decrease stroke risk in patients with nonvalvular AF.1 This condition is defined as AF in the absence of rheumatic mitral valve stenosis, a mechanical or bioprosthetic heart valve, or mitral valve repair.1 For instance, in a patient with AF and severe mitral stenosis, the anticoagulant of choice is warfarin. Conversely, in a patient with AF and severe aortic stenosis, a NOAC may be considered.Concomitant oral anticoagulation and dual antiplatelet therapy (DAPT) (aspirin and an adenosine diphosphate inhibitor)—known as triple therapy—greatly increases a patient's bleeding risk; however, NOACs can be used. The expert recommendation is to keep the duration of triple therapy as short as possible in patients who have acute coronary syndrome and AF. It is essential to accurately evaluate the patient's risk of bleeding, thrombosis, or recurrent acute coronary syndrome during triple therapy. Clopidogrel is the adenosine diphosphate inhibitor of choice; conversely, ticagrelor and prasugrel should be avoided.3,5 In DAPT plus warfarin, the target international normalized ratio is 2 to 2.5. In DAPT plus a NOAC, the NOAC prescription should be the lowest dose studied in the relevant clinical trial.3,5 Proton-pump inhibitors are recommended for patients with a risk or history of gastrointestinal bleeding, and their use is encouraged in all patients who are prescribed triple therapy.3,5 For example, in a patient with acute myocardial infarction, persistent AF, and no history of bleeding, the recommended combination would be aspirin, clopidogrel, and either a NOAC (apixaban, 2.5 mg twice daily) or warfarin.To maintain the clinical benefits and minimize the adverse effects of NOACs, clinicians must consider the pharmacologic characteristics of the particular drug, the patient's risk of bleeding, the correct drug combination with antiplatelet therapy, and potential interactions between the NOAC and the patient's other medications. In addition, all patients should be counseled about the potential side effects before they start taking NOACs.

Safety of apixaban in combination with dronedarone in patients with atrial fibrillation

BackgroundThere have been concerns about bleeding risks for patients with atrial fibrillation treated with dronedarone in combination with new oral anticoagulants (NOACs). The aim of the study was to compare the bleeding risks with the apixaban + dronedarone and warfarin + dronedarone combinations. MethodRetrospective study of Swedish nationwide health registers. All patients with atrial fibrillation who used dronedarone in combination with apixaban or warfarin during 2013–2016 were identified. Two propensity matched cohorts of each 1681 patients were compared. The main endpoint included intracranial bleeding, bleedings with hospitalization and fatal bleedings. ResultsBleedings thus defined occurred at rates of 1.31 and 2.14 per 100 years at risk with the apixaban and warfarin combinations respectively (p = 0.121). The hazard ratio with the apixaban combination was 0.66 (CI 0.35–1.23) compared to the warfarin combination. No significant differences were seen regarding secondary endpoints. ConclusionMajor bleedings were rare among patients with atrial fibrillation treated with dronedarone in combination with apixaban or warfarin. No significant differences in favour of either drug combination were found.

Epistaxis complicating treatment by anti-vitamin K and new oral anticoagulants

ObjectivesTo assess any differences in severity and management of epistaxis when complicating treatment by anti-vitamin K (AVK) or by new oral anticoagulants (NOAC). Materials and methodAll patients admitted to the ENT department of a University Hospital Center for epistaxis under oral anticoagulation therapy between January 2010 and June 2015 were included in a retrospective study. Severity was assessed in terms of management and of hemoglobin level at admission. Two groups were distinguished: treatment by AVK or by NOAC. ResultsOne hundred and thirty-four patients were included: 126 under AVK and 8 under NOAC. There was a significant difference in mean hospital stay: 4.5 days for AVK versus 3.5 days for NOAC (P=0.019; 95% CI [0.1921; 0.8907]). There were no significant differences for the other severity criteria. None of the patients died. ConclusionAdmission rates for epistaxis complicating NOAC therapy was low, and much lower than in case of AVK. Bleeding severity was equivalent with both treatments. NOACs significantly reduce hospital stay. Contrary to the study hypothesis, epistaxis is less serious when complicating NOAC than AVK therapy.

WHAT DO PATIENTS WITH ATRIAL FIBRILLATION KNOW ABOUT STROKE AND SYSTEMIC EMBOLISM PREVENTION? DATA OF THE PRIMA-TERRA REGISTRY

Aim. To study the awareness and opinion of patients with atrial fibrillation (AF) about the stroke prevention. Material and methods. This study based on the questionnaire survey of 544 patients from three regions of Russia is the third part of the PRIMA-TERRA register. The survey was carried out in the period from 01.12.2012 to 01.07.2013 by independent employees on a special questionnaire of 9 questions. The ratio of men and women was 42% vs 58%, respectively, the average age was 65.6Ѓ}8.2 years. The AF duration was 7.6Ѓ}2.0 years. The average score of CHA2DS2-VASc was 3.4Ѓ}1.4. Results. Less than 70% of patients were informed of possible AF complications, of which less than a third – about the risk of stroke. Only 62% of patients believed that they take drugs for the stroke prevention, of which only 31% took warfarin, 15% new oral anticoagulants (NOAC). The majority of patients received antiplatelet agents and their combinations – medications not recommended for this purpose by modern National and European cardiology guidelines. Less than 60% of the respondents were informed about the NOACs, while clinically significant information about the benefits of this group of drugs was provided by doctors only to 18% of patients. The main reason limiting the widespread use of NOACs is the high cost of these drugs. Conclusion. Awareness of patients about AF thromboembolic complications is extremely inadequate. For the prevention of stroke, most patients take antiplatelet agents and their combinations, less than a half – anticoagulants. The main reason for refusing to receive the NOACs is the high cost of this group of drugs.