Effect Of New Oral Anticoagulants Research Articles

Effect of uninterrupted dabigatran or rivaroxaban on achieving ideal activated clotting time to heparin response during catheter ablation in patients with atrial fibrillation.

Uninterrupted use of oral anticoagulants before atrial fibrillation (AF) ablation can reduce the incidence of perioperative thromboembolic events. However, the effect of new oral anticoagulants on activated clotting time (ACT) in response to heparin during AF ablation in Chinese populations remains unknown. The aim of the present retrospective study was to investigate the value of ACTs in response to intraoperative heparin administration in patients using dabigatran or rivaroxaban. From January 2018 to December 2021, a total of 173 patients undergoing AF ablation were included in the study, in which 101 patients were treated with dabigatran, 72 patients were treated with rivaroxaban. The intraoperative ACT values were examined in both groups. The incidence of periprocedural complications was evaluated. Initial heparin dosage (88 ± 19 U/kg vs. 78 ± 27 U/kg, P < 0.05), total heparin dosage (137 ± 41 U/kg vs. 106 ± 52 U/kg, P < 0.05) during the ablation procedure were higher in the dabigatran group than those in the rivaroxaban group. Mean ACT (280 ± 36 s vs. 265 ± 30 s, P < 0.05), and the percentage of ACTs within the therapeutic range (250-350 s) (74% ± 26% vs. 60% ± 29%, P < 0.05) were significantly lower in the dabigatran group than those in the rivaroxaban group, particularly in male patients. Furthermore, the average time of achieving the target ACT (250-350 s) was also found longer in the dabigatran group (P < 0.05) as compared with the rivaroxaban group. No significant difference was found in the incidence of periprocedural complications between the two groups. The anticoagulant effect of uninterrupted rivaroxaban therapy appears to be more stable and efficient than dabigatran administration during catheter ablation in patients with AF.

Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation.

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima–media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Analysis of the Introduction in Clinical Practice of New Oral Anticoagulants in Local Health Agency BT: Translation of the Clinical Trial Data to a Local Health Care Area.

The commercial release of the New Oral Anticoagulants (NOACs) has been the most significant change in anticoagulant therapy in recent years. The work aimed to evaluate the economic and health impact for the Local Health Agency Barletta-Andria-Trani (BT). Through the Regional Information System data about naïve patients on NOAC treatment and patients on anti-vitamin-k (VKA), treatments were extrapolated. We assessed therapeutic continuity, pharmaceutical expenditure, hospitalizations, and deaths in 2017 and 2018. Therapeutic continuity was similar in the two groups. The number and the average cost of hospitalizations for a patient treated with VKAs were almost constant, while those of patients treated with NOACs decreased. The treatment of adult-aged naïve patients with NOACs, compared to VKAs therapy, involves an increase in expenditure of about 100€ for a patient, but the reduced hospitalizations could generate, in the long term, saving for the Health System. Clinical data, according to the Real-World Data, confirmed the safety and effectiveness of these drugs. However, attention to the special population is necessary to improve the safety and effectiveness of NOACs. Innovative formulations for pediatric patients are being developed. The challenge for Health Systems is the appropriate use of available resources through health interventions with transversal competences.

New Oral Anticoagulants for Thromboprophylaxis in Patients with Cancer Receiving Chemotherapy: An Economic Evaluation in a Chinese Setting.

Recent trials showed that thromboprophylaxis with new oral anticoagulants (NOACs) is effective and safe in patients with cancer initiating chemotherapy. However, the cost effectiveness of NOACs is unknown. The objective of this study was to compare the cost effectiveness of preventing venous thromboembolism with NOACs with no thromboprophylaxis for patients with cancer initiating systemic chemotherapy from the perspective of the Chinese healthcare system. A decision analytical model consisting of both acute and chronic venous thromboembolism complications was used to assess the cost effectiveness of thromboprophylaxis with NOACs vs no thromboprophylaxis. The key clinical data were derived from the CASSINI and AVERT trials. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies. Scenario and sensitivity analyses were performed. Compared with no thromboprophylaxis, NOACs gained 0.072 QALY at an incremental cost of $US930, leading to an ICER of 12,919/QALY in patients with Khorana scores ≥ 2 by pooling the data from the CASSINI and AVERT trials. Among patients confirmed with no deep-vein thrombosis before thromboprophylaxis (the CASSINI trial) and patients without deep-vein thrombosis screening before thromboprophylaxis (the AVERT trial), the ICERs were $70,897/QALY and $87,204/QALY, respectively. The probability of NOACs being cost effective was 42% at a willingness to pay of $10,276/QALY. The ICER was sensitive to the relative risks of death and asymptomatic venous thromboembolism between NOACs and no thromboprophylaxis and the cost of NOACs. Thromboprophylaxis with NOACs is not likely to be cost effective in patients initiating chemotherapy in the Chinese context. The decision about thromboprophylaxis should be tailored based on the survival of patients with cancer, the risks of venous thromboembolism, and major bleeding.

Use of New Oral Anticoagulants / Direct Oral Anticoagulants in Malignant Patients.

Vitamin K antagonists are being used in the last five decades as an effective anticoagulant. However, for the past few years, new oral anticoagulants (NOACs) have been introduced as newer anticoagulant agents, which are gradually replacing the previously used vitamin K antagonist. Yet, these agents have not fully replaced the use of warfarin and heparin. NOACs have few advantages over the vitamin K antagonist as they act on a specific factor of coagulation cascade rather than inhibiting the whole vitamin K synthesis.In this article, all the data has been searched electronically on PubMed and PRISMA guidelines were not followed. Instead, we used MOOSE statements and the data searched on PubMed was from articles published in the last five years.A total of 12,269 patients were observed;,out of which 64.19% had active cancer and 35.80% was observed as a control group comprised of both male or female participants. Approximately 61.14% were using NOACs, 42.83% were on warfarin, and 2.72% were on low-molecular-weight heparin (LMWH). The NOACs used in different patients were in the following percentages; edoxaban (6.81%), apixaban (5.28%), dabigatran (10.09%), and rivaroxaban (10.02%).The use of NOACs has been increasing day by day but these agents have not completely replaced the warfarin or heparin, because of some demerits associated with the use of warfarin and some conditions where these drugs should be avoided. All NOACs have either hepatic or renal clearance so the hepatic activity and creatinine clearance rate must be monitored before the start of NOACs. The drug interaction between anticancer drugs and NOACs is still not fully reported.The effects of NOACs in AF and VTE are therapeutically effective, but in oncology patients several other co-factors are also involved with the use of NOACs due to which, it is either contraindicated or in some cases dose adjustment is required. However, very little information has been collected and more investigation must be done in this perspective.

Effect of new oral anticoagulants on platelet indices in non-valvular atrial fibrillation patients

New-generation oral anticoagulants (NOACs) are now preferred as afirst-line treatment in the management of atrial fibrillation for prevention of thromboembolic complications. Mean platelet volume (MPV), one of the indicators of increased platelet activity, is also associated with an increased stroke risk in atrial fibrillation patients. The aim of this study was to evaluate changes in MPV, platelet distribution width (PDW) and plateletcrit following use of NOACs. The study included 116patients with non-valvular atrial fibrillation without previous NOAC use. Complete blood counts, biochemical analyses and echocardiography were performed for all patients. No significant differences were observed in MPV or other platelet indices at 6months compared to baseline. Our results indicate that MPV and other platelet indices are not affected by NOAC use in non-valvular atrial fibrillation patients.

Effect of antithrombotic drugs on bone health.

With the increasing consumption of antithrombotic drugs among old people, expected as well as unexpected side effects on bone health are considerable, e.g. osteoporosis, fragility fractures, etc. This review focuses on antithrombotic drugs and their effects on bone health. The following groups were reviewed: parenteral long-term use of unfractionated heparin (UFH) is associated with osteopenia. The oral intake of vitaminK antagonists (VKA) makes them more convenient than UFH but chronic use also results in osteopenia. Limited reports of bone loss have been associated with low molecular weight heparins (LMWH) and indirect factor Xa inhibitors but in contrast to VKA and UFH they are less associated with osteopenia. There have been limited studies evaluating the effect of new oral anticoagulants (NOACs) on bones. Overall, they are considered safer than other drugs. There have been no reports about acetylsalicylic acid (ASA) and clopidogrel causing osteopenia but their metabolism by the kidneys and liver can cause reduced 25-hydroxy-vitaminD levels and can theoretically contribute to osteoporosis. Some reports suggested that high dosage clopidogrel can also negatively affect bones. After adetailed literature review long-term use of antithrombotic drugs can negatively affect the bones. Their role in bone health needs to be studied in detail and the clinical use in geriatric patients should be prudent.

PLEIOTROPIC EFFECTS OF ORAL ANTICOAGULANTS

In this paper, we present a literature review with the purpose of elucidating the pleiotropic effects of oral anticoagulants. The literature search was performed using the PubMed and SCOPUS databases. Pleiotropic effects of direct anticoagulants are determined by the interaction of Xa and thrombin IIa factors with PAR-1 and PAR-2 receptors. The focus of this review is the connection between oral anticoagulants and their effects on atherosclerosis, angiogenesis, inflammation, cardiac remodelling, oncogenesis and glomerular diseases. Direct anticoagulants exhibit an anti-atherosclerotic effect manifested in a decreased progression and destabilization of atherosclerotic lesions. This effect is confirmed by a decreased binding activity of DNA with NF-kB and AP-1 transcription factors and reduced levels of some mediators. Such effects of new oral anticoagulants also relate to the processes of cardiac remodelling. FXa inhibitors contribute to the prevention of cardiac remodelling by reducing the processes of inflammation and fibrosis, which are associated with a decrease in the expression of PAR receptors in the heart. A number of studies also demonstrate an anti-inflammatory effect of oral anticoagulants, which is confirmed by reduced expression of mRNA inflammatory cytokines under the influence of direct anticoagulants and the production of IL-6 under the influence of warfarin. FXa inhibitors are shown to increase the expression of vascular growth factors, stimulate the migration of еndothelial рrogenitor сells and improve their function, thus manifesting their angiogenic pleiotropic effect. In addition, warfarin has an impact both on angiogenesis by means of reducing the activation of Axl tyrosine kinases and on glomerular pathologies by means of affecting the proliferation of mesangial cells through the Gas6/Axl pathway. The antitumour activity of warfarin is associated with inhibition of Gas6-mediated activation of Axl on tumour cells. Further investigations are required to fully understand the effect of oral anticoagulants on haemostasis.

USING A 1:1:1 PROPENSITY SCORE MATCHED COHORT TO ANALYZE THE COMPARATIVE EFFECTIVENESS OF NEW ORAL ANTICOAGULANT THERAPY USED FOR STROKE PROPHYLAXIS IN NON-VALVULAR ATRIAL FIBRILLATION

Only recently have differences in the real-world effectiveness of new oral anticoagulants (NOAC) come to light. The objective of this study was to examine differences in clinical outcomes and cost of NOAC for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Retrospective

Introduction and interpretation of guidelines on thromboprophylaxis in the perioperative period of urological surgery

Venous thromboembolism had drawn great attention of global experts, as it is the third leading cause of cardiovascular-associated death, ranking after coronary heart disease and stroke. Numerous health care organizations had introduced guidelines for thromboprophylaxis during the perioperative period in their own fields. The paper reviewed the available guidelines pertaining to urological surgery from America Urological Association, American College of Chest Physicians and European Association of Urology. Compared with the first two guidelines, the European Association of Urology guideline is a milestone which recommended the most detailed prophylactic measures for the procedure-specific and patient-specific according to the evidence-based medicine. Meanwhile, there was still no reliable evidence in fields of the effect of new oral anticoagulants in urology, needing further study. Although they were similar in patient management and prophylaxis principles, there are still some differences in risk factors, assessments, and recommendations of prophylactic measures. In this context, we planed to summarize the highlights and compare the differences of three guidelines addressing the use of thromboprophylaxis in urology, in order to provide reference for Chinese urologists to select the best prevention strategies for patients in the perioperative period.

Evaluation of activated charcoal and lipid emulsion treatment in model of acute rivaroxaban toxicity

AimReducing or reversing the toxicity effects of new oral anticoagulants is an important question.The purpose of the present study is to evaluate the effect of lipid emulsion (LE) and Activated Charcoal (AC) therapy on the intoxication of rivaroxaban, on mice. MethodsAdult male Balb/c mice weighing approximately 30g were used in the study. Seven groups were assigned, with six mice in each group. Groups were defined; given only rivaroxaban, given only LE, given only AC, after the administration of rivaroxaban LE applied group in the 1st hour, after the administration of rivaroxaban LE applied group in the 3rd hour, after the administration of rivaroxaban AC applied group in the1st hour, after the administration of rivaroxaban AC applied group in the 1st hour and LE applied group in the 3rd hour. PT and Anti-Factor Xa activity were measured in all blood samples from subjects. ResultsA statistically significant difference was found when all groups were compared in terms of mean PT values and Anti-FactorXa values. However, no statistically significant difference was found in the mean PT and Anti-FactorXa values when only rivaroxaban administrated group and after the administration of rivaroxaban LE and/or AC applied groups were compared one to one. No deaths occurred in groups during the observation. ConclusionAlthough the administration of either AC or LE alone or in combination resulted in a decrease in the mean values of PT and anti-Factor Xa, in case of rivaroxaban toxicity, but one-to-one comparison of the groups was not statistically significant.

Effect of New Oral Anticoagulants on Prescribing Practices for Atrial Fibrillation in Older Adults.

To determine the effect of new oral anticoagulants (NOACs) on prescribing practices in older adults with atrial fibrillation (AF). Retrospective observational cohort study. Academic medical center in St. Louis, Missouri. Individuals aged 75 and older with AF admitted to the hospital from October 2010 through September 2015 (N = 6,568, 50% female, 15% non-white). Information on NOACs and warfarin prescribed at discharge was obtained from hospital discharge summaries, and linear regression was used to examine quarterly trends in their use. Multivariable logistic regression was used to assess independent predictors of anticoagulant use. NOAC use increased over time (correlation coefficient (r) = 0.87, P < .001), warfarin use did not change (r = -0.16, P = .50), and overall anticoagulant use (NOACs and warfarin) increased (r = 0.68, P = .001). NOAC use increased over time in all age groups (75-79, 80-84, 85-89) except aged 90 and older, but increasing age attenuated the rate of NOAC uptake. There was no consistent relationship between age and warfarin or overall anticoagulant use, except that individuals aged 90 and older had consistently lower use. Overall, fewer than 45% of participants were prescribed an anticoagulant. In multivariable analysis, younger age, white race, female sex, higher hemoglobin, higher creatinine clearance, being on a medical service, hypertension, stroke or transient ischemic attack, no history of intracranial hemorrhage, and a modified HAS-BLED score of less than 3 increased the likelihood of receiving NOACs. Prescription of anticoagulants for AF increased in older adults primarily because of an increase in the use of NOACs. Nonetheless, fewer than 45% of participants were prescribed an anticoagulant. Additional research is needed to optimize prescribing practices for older adults with AF.

P1658Clinical effectiveness of new oral anticoagulants in US and Europe for stroke prevention in atrial fibrillation

P1658Clinical effectiveness of new oral anticoagulants in US and Europe for stroke prevention in atrial fibrillation

Evaluation of the vascular protective effects of new oral anticoagulants in high-risk patients with atrial fibrillation (PREFER-AF): study protocol for a randomized controlled trial.

BackgroundAtrial fibrillation (AF) is known to be associated with several pathophysiological mechanisms including endothelial dysfunction of the heart and arterial vessels. Recent evidence suggests that new oral anticoagulant (NOAC) treatment may improve endothelial function and the inflammatory process involved in atherosclerosis in AF patients. This study is designed to determine the efficacy of NOAC therapy in the prevention of endothelial dysfunction and the progression of atherosclerosis of AF subjects.Method/designAF patients with a CHA2DS2-VASc score >2 and no previous history of overt coronary disease, severe peripheral arterial disease (PAD) or major stroke will be registered and randomly assigned either to the NOAC group (dabigatran or rivaroxaban) or the warfarin group in this prospective, randomized, 2-year follow-up study. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function will be conducted using the Endo-PAT2000 device. Left and right carotid intima-media thickness (IMT) will be measured at baseline, 12 months, and 24 months. The primary endpoint is defined as change in Reactive Hyperemia Index (RHI) at 12 months. Secondary endpoints included changes in the right and left maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA), the mean IMT of the CCA and ICA at 24 months, and 24-month cardiovascular events including cardiac death, stroke, acute myocardial infarction (AMI), overall cause of death, withdrawal of drug, or bleeding events.DiscussionThis is the first study to evaluate the efficacy of NOAC therapy for the prevention of endothelial dysfunction and progression of atherosclerosis in AF subjects. These findings are expected to expand the knowledge of NOAC pleotropic action in AF patients.Trial registrationClinicalTrials.gov: NCT02544932, registered on 7 September 2015.

New anticoagulants in clinical practice. Effectiveness and problems

We analyze the effectiveness of new oral anticoagulants and antivitamins K for the treatment of patients with venous problems, atrial fibrillation, and acute coronary syndrome with reference to advantages of this therapy and methods of prevention of complications of these conditions.

New oral anticoagulants in patients with cancer: current state of evidence.

Effectiveness of new oral anticoagulants (NOAC) in patients with cancer is not clearly defined. There remain concerns of doubtful benefit and chances of potential harm with newer agents. In this meta-analysis, we evaluated the efficacy and safety of NOAC in patients with cancer. PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials reporting efficacy and safety data of NOACs (rivaroxaban, dabigatran, and apixaban) with control (low-molecular-weight heparin/vitamin K antagonists/placebo) for patients with cancer were included. Primary efficacy outcome was venous thromboembolism (VTE) or VTE-related death, and primary safety outcome was clinically relevant bleeding. We used random-effects models. Six trials randomized 19,832 patients, and 1197 patients had cancer. Risk of VTE or VTE-related death was not significantly different with NOAC versus control [odds ratio (OR), 0.80; 95% confidence interval (CI), 0.39-1.65] in patients with cancer. Separate analysis for individual effects showed similar results for rivaroxaban (OR, 1.08; 95% CI, 0.60-1.94) and dabigatran (OR, 0.91; 95% CI, 0.21-3.91). Clinically relevant bleeding was not higher with NOAC compared with control (OR, 1.49; 95% CI, 0.82-2.71); individual effect of rivaroxaban showed similar results. No statistically significant difference of efficacy and safety with NOAC was found between patients with and without cancer. Rivaroxaban might be equally effective and safe as vitamin K antagonist in patients with cancer. Dabigatran is as effective as comparator; however, safety profile of dabigatran is unknown. Randomized trials of new anticoagulants specific to the cancer population are necessary, and NOAC also need to be evaluated against low-molecular-weight heparin.

The effect of new oral anticoagulants and extended thromboprophylaxis policy on hip and knee arthroplasty outcomes: observational study.

The efficacy and safety of the new oral anticoagulants (NOAC) and the benefits of extended duration thromboprophylaxis following hip and knee replacements remain uncertain. This observational study describes the relations between thromboprophylaxis policies following hip and knee replacements across England's NHS and patient outcomes between January 2008 and December 2011. From the national administrative database, we analyzed mortality, thromboembolic complications, emergency readmission, and bleeding rates for 201,418 hip and 230,282 knee replacements. There were no differences in outcomes for either LMWH or NOAC. We found no advantage in favor of any single anticoagulation policy or in changing policy. This study supports the American Academy of Orthopaedic Surgeons' recommendation that the choice and duration of thromboprophylaxis prophylaxis be decided by the treating surgeon.

Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis

ObjectiveIn recent years, safety alerts have been made warning of the risk of serious drug-induced liver injury (DILI) caused by cardiovascular drugs. The new oral anticoagulants (NOACs) have now reached...

Stroke Prevention in Atrial Fibrillation: The Roles of Anticoagulants, Devices, and Antidotes

This article reviews tools for risk stratification for stroke and bleeding among patients with atrial fibrillation (AF). The CHADS2 score is frequently used to estimate the risk of stroke in AF patients and to help determine the appropriateness of anticoagulant therapy. Also discussed are the benefit-risk of warfarin and the new oral anticoagulants (OACs), multiple clinical trials, as well as the measurement and monitoring of the anticoagulant effects of new OACs.

New Oral Anticoagulants Are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons

PurposePatients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).MethodsThree randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively.ResultsIn patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban.ConclusionNOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding.