Use Of Non-vitamin K Oral Anticoagulants Research Articles

Non-vitamin K oral anticoagulants versus warfarin for the treatment of left ventricular thrombus.

Left ventricular thrombus (LVT) is associated with significant morbidity and mortality. Conventional treatment comprises warfarin-mediated anticoagulation; it is unclear whether non-vitamin K oral anticoagulants (NOACs) exhibit comparable efficacy and safety. Limited data are available for Asian patients. This study compared NOACs with warfarin in terms of clinical efficacy and safety for managing LVT. Clinical and echocardiographic records were retrieved for all adult patients with echocardiography-confirmed LVT at a major regional centre in Hong Kong from January 2011 to January 2020. Discontinuation of anticoagulation by 1 year was recorded. Outcomes were compared between patients receiving NOACs and those receiving warfarin. Primary outcomes were cumulative mortality and net adverse clinical events (NACEs). Secondary outcomes were complete LVT resolution and percentage reduction in LVT size at 3 months. Forty-three patients were included; 28 received warfarin and 15 received NOACs, with follow-up periods (mean ± standard deviation) of 20 ± 12 months and 22 ± 9 months, respectively (P=0.522). Use of NOACs was associated with significantly lower NACE risk (hazard ratio [HR]=0.111, 95% confidence interval [CI]=0.012-0.994; P=0.049) and a tendency towards lower cumulative mortality (HR=0.184, 95% CI=0.032-1.059; P=0.058). There were no significant differences in secondary outcomes. Considering LVT resolution, discontinuation of anticoagulation by 1 year was not significantly associated with different outcomes. Non-vitamin K oral anticoagulants may be an efficacious and safe alternative to warfarin for LVT management. Future studies should explore the safety and efficacy of anticoagulation discontinuation by 1 year as an overall strategy.

Gender Differences in Atrial Fibrillation: From the Thromboembolic Risk to the Anticoagulant Treatment Response

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased thromboembolic risk. The impact of the female sex as an independent risk factor for thromboembolic events in AF is still debated. Background and Objectives: The aim of this review is to evaluate the gender-related differences in cardioembolic risk and response to anticoagulants among AF patients. Materials and Methods: The PubMed database is used to review the reports about gender differences and thromboembolic risk in atrial fibrillation. Results: Non-vitamin K oral anticoagulants (NOACs) represent the gold standard for thromboembolic risk prevention in patients with non-valvular atrial fibrillation (NVAF). Despite a similar rate of stroke and systemic embolism (SE) among men and women in NOACs or vitamin K antagonists (VKAs) treatment, the use of NOACs in AF women is associated with a lower risk of intracranial bleeding, major bleeding, and all-cause mortality than in men. Conclusions: The female sex can be defined as a stroke risk modifier rather than a stroke risk factor since it mainly increases the thromboembolic risk in the presence of other risk factors. Further studies about the efficacy and safety profile of NOACs according to sex are needed to support clinicians in performing the most appropriate and tailored anticoagulant therapy, either in male or female AF patients.

Abstract 12361: Efficacy and Safety of NOACs vs. Warfarin Across the Continuous Range of Body Mass Index and Body Weight: Insights From COMBINE-AF

Introduction: The efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at the extremes of body mass index (BMI) and body weight (BW) remains uncertain, leading to concerns regarding use in these populations across clinical practice guidelines. Methods: This analysis of the COMBINE-AF database pools individual patient-level data from the 4 pivotal RCTs of NOAC vs. warfarin in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Pts randomized to low-dose NOACs not globally approved for clinical use were excluded. The primary efficacy and safety outcome was stroke/systemic embolic event (S/SEE) and major bleeding, respectively, with intracranial hemorrhage (ICH) being a secondary outcome. Outcomes were assessed across BMI and BW using a Cox model stratified by trial, with interaction testing for NOAC vs. warfarin. Restricted cubic splines were used to display the hazard ratio of NOAC vs. warfarin for each outcome across BMI. Results: For 58,464 pts, the median BMI was 28 (25 th -75 th %ile: 25-32) kg/m 2 , with the top 5% (n=2,924) having a BMI ≥ 40 kg/m 2 . For patients randomized to warfarin, the risk of each outcome was lower with increasing BMI (HR per 5 kg/m 2 increase: S/SEE 0.79 [95% CI 0.75-0.84]; major bleeding 0.91 [95% CI 0.87-0.95]; ICH 0.72 [95% CI 0.66-0.80]; p<0.01 for each). There was no significant treatment interaction for NOAC vs. warfarin by BMI for S/SEE (p-interaction = 0.71; Fig 1A ), major bleeding (p-interaction = 0.15; Fig 1B ), or ICH (p-interaction = 0.84; Fig 1C ), such that there was consistent reduction in S/SEE and ICH ( Fig 1A and 1C, respectively ) across the range of BMI with NOAC vs. warfarin. Similar results were seen for each outcome when assessed by BW (median [25 th -75 th %ile]: 81 [70-94] kg; 5 th -95 th %ile: 55-119 kg). Conclusions: In this pooled analysis of the pivotal AF trials, use of NOAC was associated with a consistent reduction in S/SEE and ICH compared with warfarin across the range of BMI and BW.

NOAC in adult congenital heart disease patients: a single-center experience

Abstract Background Adult Congenital Heart Disease (ACHD) patients at increased risk for thromboembolic events are often treated with oral anticoagulation. While vitamin-K antagonists have been the agent of choice for decades, the use of non-vitamin K oral anticoagulants (NOAC) is increasing. We aimed to assess the safety and effectiveness of NOAC in ACHD patients at our centre. Methods This is a single-centre study enrolling all patients with ACHD treated with a NOAC from inception to November 2021. Data was collected using a standardized questionnaire applied to all patients by means of a telephone visit, in parallel with a detailed retrospective chart review. The endpoints of interest included thromboembolic and haemorrhagic events, defined as per the standardized International Society on Thrombosis and Haemostasis (ISTH) scale. Results Overall, 36 ACHD patients were enrolled [mean age 53±15 years; female sex – 66.7%; previous stroke – 33.3%; median HAS-BLED and CHA2DS2-VASc score – 1 (1–2) and 3 (2–5), respectively], predominantly with moderate or complex congenital defects (52.7%), of whom 14, 8, 8 and 4 were treated with rivaroxaban, apixaban, edoxaban and dabigatran, respectively. Two-thirds had their first NOAC prescription in the latest 3 years (Figure 1). The most common indication for anticoagulation was atrial fibrillation or flutter (77.8%). Over a median time of 36 (18–63) months on NOAC treatment, there were no patients with thromboembolic events, whilst 13 (36.1%) had a haemorrhagic event – annualized event rate of 12.0 (6.9–24.1%). All bleeding events were minor, most often self-limited gingival haemorrhage or epistaxis (n=7) or menorrhagia (n=3). Nasal cautery was needed to treat recurrent epistaxis in 3 patients, whilst 3 other required oral iron supplementation. The strongest predictor of any haemorrhage was a prior cardiovascular hospitalization (HR 3.88; p=0.027). Conclusions The use of NOAC in ACHD patients has been increasing in our centre, with encouraging results. The present findings suggest that NOAC are safe and may be effective for thromboembolic event prevention in heterogeneous forms of ACHD. Funding Acknowledgement Type of funding sources: None.

Abstract 12301: Anticoagulation for Left Ventricular Thrombus: An Updated Meta-Analysis of Stroke or Systemic Embolization Outcomes

Introduction: Thromboembolic events including stroke or systemic embolization (SSE) are the most dreaded complications in patients who develop left ventricular (LV) thrombus. Vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) have been used in the management of LV thrombus however the efficacy of these treatment strategies have been rarely studied in head-to-head trials. Our aim was to study the differences in embolization outcomes in patients with LV thrombus on either NOACs or VKAs. Methods: A comprehensive search of electronic databases was conducted for studies comparing VKAs and NOACs in patients with LV thrombus. Event level data were extracted from studies for each arm and used to calculate the risk ratio (RR) with 95% confidence intervals (CI) which were pooled for the effect of original treatment allocation on the outcome of SSE. Random effects model was used to calculate the risk ratio. Results: We found a total of 12 studies from which 2281 patients were identified with LV thrombus and were treated with anticoagulation. 596 (26.13%) received NOACs and 1685 (73.87%) received VKAs. Events of SSE occurred in 92 (15.44%) patients on NOACs and 307 (18.22%) patients on VKAs. Overall, patients treated with NOACs had similar rate of SSE events as compared to patients treated with VKAs using random effects model (RR: 1.02 [95% 0.64-1.65], p=0.08, I 2 =39%). Conclusions: This meta-analysis suggests that the use of NOACs is associated similar rate of SSE events in patients with LV thrombus as compared to the use of VKAs. Additional prospective studies are required to determine the most effective anticoagulant strategy for patients with LV thrombus.

Prophylactic anticoagulation in sinus rhythm for stroke prevention in cardiovascular disease: contemporary meta-analysis of large randomized trials.

Anticoagulation with non-vitamin K oral anticoagulants (NOACs) to prevent stroke is a mainstay of atrial fibrillation (AF) management. However, multiple cardiovascular diseases (CVDs) are associated with elevated ischaemic stroke risk even in sinus rhythm. In this meta-analysis, we assess efficacy and safety of prophylactic NOAC agents for stroke prevention in patients without AF. A search was conducted for randomized controlled trials (RCTs) that evaluated an NOAC and control drug (placebo or antiplatelet) in non-AF patients with mixed CVD. The primary efficacy and safety outcomes were ischaemic stroke and major bleeding, respectively. Results were stratified based on primary- and mini-NOAC doses. Thirteen RCTs were identified with a total of 89 383 patients with CVD in sinus rhythm (53 778 on NOAC, 35 605 on control drug; mean age 65.5 ± 2.7 years). Over a mean follow-up of 18.3 months, 1429 (1.6%) ischaemic strokes occurred. Use of NOAC was associated with 26% reduction in stroke [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.62-0.87; 1.1 vs. 1.8 events per 100 person-years], with numbers needed to treat of 153 patients to prevent one stroke. Major bleeding was increased with NOAC (OR 1.74, 95% CI 1.44-2.09; 2.1 vs. 1.0 events per 100 person-years). The weighted net clinical benefit (wNCB, composite of ischaemic stroke and bleeding) did not suggest a favourable effect with any NOAC dose (wNCB for primary-dose: -0.35; mini-dose: -0.06). Current evidence does not support use of NOACs for stroke prevention in non-AF CVD population as risk of major bleeding still exceeds ischaemic stroke benefit.

Efficacy and Safety of Nonvitamin K Oral Anticoagulants following Cardiac Valve Replacement.

To compare the efficacy and safety of nonvitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) following bioprosthetic cardiac valve replacement. This was a retrospective analysis conducted at a community teaching hospital in the southeastern United States between August 2015 and August 2018. Patients 18 years of age and older who underwent cardiac valve replacement and were prescribed oral anticoagulation were screened for inclusion. Patients were excluded if they had a mechanical valve replacement, experienced a venous thromboembolism, cerebrovascular accident, or acute coronary syndrome within 1 month before valve replacement, changed oral anticoagulation during the study period, were lost to follow-up, or declined to participate in the follow-up survey. The primary outcome was a composite of thromboembolic events within 90 days following bioprosthetic cardiac valve replacement. The safety outcome was major bleeding within 180 days of bioprosthetic cardiac valve replacement. The primary outcome of a composite of thromboembolic events within 90 days following bioprosthetic cardiac valve replacement occurred in 1 patient (4.3%) in the VKA group and 4 patients (7.4%) in the NOAC group. Major bleeding occurred in 2 patients (8.7%) in the VKA group and 0 patients in the NOAC group. Our study is the first to report the efficacy and safety of NOACs compared with VKA therapy following bioprosthetic cardiac valve replacement irrespective of an atrial fibrillation diagnosis. Notably, two of the thromboembolic events in the NOAC group occurred while therapy was held or inappropriately dosed; when these events are removed, the rate of thromboembolism is 3.8%. This rate is consistent with the VKA group. Our study adds to a small pool of literature regarding the use of NOACs following bioprosthetic cardiac valve replacement and suggests that NOACs may have similar efficacy and improved safety as compared with VKA therapy. Large randomized controlled trials are warranted to confirm our observations.

Heartbeat: increased use of NOACs in patients with atrial fibrillation reduces health care system costs by reducing stroke incidence

A major goal in management of adults with atrial fibrillation (AF) is prevention of stroke. In an editorial, our stroke neurology colleagues1 point out that about 1/3 of patients with...

S1230 Non-Vitamin K Oral Anticoagulants (NOACs) vs Low Molecular Weight Heparin (LMWH) for the Treatment of Venous Thromboembolism in the Setting of Gastrointestinal and Pancreato-Biliary Malignancies—A Meta-Analysis

INTRODUCTION: The safety and efficacy of NOAC use compared with low molecular weight heparin (LMWH) use, the current standard of care for the treatment of gastrointestinal and pancreatobiliary cancer associated venous thromboembnolism (GI-CAVTE), has not been well studied. METHODS: A systematic review of Medline and Embase was conducted from inception to April 2020 to identify studies reporting the use of NOACs and LMWH for the treatment of GI-CAVTE. A meta-analysis of proportions as well as a comparative meta-analysis was performed to assess safety and efficacy. GI bleeding events were recorded and reported descriptively. RESULTS: Three observational studies enrolling 561 patients (213 on NOACs; 348 on LMWH) were found, 154 of whom were females. Pancreatobiliary malignancies were the most common in the NOAC group (N = 79), followed by gastric cancer (N = 41) and colorectal cancer (N = 21). In contrast, gastric cancer was the most common malignancy in the LMWH arm (N = 149), followed by pancreatobiliary malignancy(N = 135), and colorectal cancer (N = 11). The risk of bias as assessed by the ROBINS-I tool was moderate in 1 and serious in 2 studies. The OBR was 29% (23–35) with NOAC use, of which 28% (16–40%) were major bleeds and 81% (70-91%) were CRNMB. In contrast, the OBR with LMWH use was 20% (16–24%), of which 38% (26–49%) were major bleeds and 67% (56–78%) were CRNMB. Fatal bleeding events occurred in 7% (0–15%) of patients on NOACs and 9% (1–16%) of patients on LMWH. The risk of OBR was higher with NOAC use (RR 1.61; 1.19-2.19; I2 = 37.4%), as was the risk of CRNMB (RR 1.86; 1.27-2.72; I2 = 0%). However, no difference in major bleeding and fatal bleeding risk was found with NOAC versus LMWH use. Table 1 summarizes the reported gastrointestinal bleeding events across studies. The rVTE rate was 4% (1–6%) with NOAC use and 2% (1–4%) with LMWH use. There was no difference in the risk of rVTE, rDVT, rPE, or fatal VTE with NOAC versus LMWH use. CONCLUSION: NOACs may pose a greater risk of bleeding, particularly CRNMB, in patients with GI-CAVTE. We did not identify any signal of superior efficacy in term of rVTE, rDVT, or rPE risk with NOAC use compared with LMWH. The risk of bleeding from luminal malignancies while on NOACs remains to be studied further before any conclusions can be made. on Due to lack of randomized trials and a high number of observational studies, our findings are hypothesis generating at best, and further studies are needed to validate our findings.Table 1.: Reported Gastrointestinal Bleeding with DOAC and LMWH Use. CRNMB = Clinically relevant non-major bleeding; GI = gastrointestinalFigure 1.: Meta-Analysis of Proportions - Safety and Efficacy Endpoints - NOACs vs LMWH.Figure 2.: Comparative Meta-Analysis of Safety and Efficacy - NOAC vs LMWH.

Non-vitamin K oral anticoagulants in hypertrophic cardiomyopathy patients undergoing catheter ablation of atrial fibrillation.

Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to high thromboembolic risk. Evidence supporting the use of non-vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in patients with HCM undergoing catheter ablation of AF. Observational nonrandomized study in four European centers. We aimed to investigate the safety and efficacy of NOACs compared with vitamin K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF. A total of 137 patients with HCM (mean age: 55.0 ± 13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7 ± 1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure-related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA: 0.6%; NOAC: 0%; p = 1.0) or minor bleeding (VKA: 0.6%; NOAC: 1.4%; p = .54). There was a nonsignificant trend towards a lower incidence of major bleeding (VKA: 6.9%; NOAC: 1.4%; p = .09). These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF.

Racial Disparity in the Prescription of Anticoagulants and Risk of Stroke and Bleeding in Atrial Fibrillation Patients

Background: Oral anticoagulant (OAC) therapy is proven to be effective at reducing risk of stroke in patients with atrial fibrillation (AF). However, racial minorities with AF are less likely to be prescribed vitamin K anticoagulants (VKA). There is little information on the racial disparity in the prescription of the non-vitamin K oral anticoagulants (NOACs) and the associated risks of stroke and bleeding. Methods: We used data from the Northwestern Medicine Enterprise Data Warehouse – a joint initiative across 11 Northwestern Medicine affiliated healthcare centers within metropolitan Chicago, Illinois. Newly diagnosed AF patients between Jan, 2011 and Dec, 2017 with CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, female sex) score of 2 or more and no prior history of stroke or major bleeding were eligible. Logistic regression was used to examine differences in the prescription of any OAC and NOACs by race. Racial differences in the associations of NOACs prescription with incident stroke (a composite of ischemic and hemorrhagic stroke and cerebral embolism) and major bleeding were evaluated using Cox regression. Results: Among 11,575 newly diagnosed AF patients with CHA2DS2VASc score of 2 or more, 48.7% (47.8-49.6) were on any OAC and among those 40.1% (38.8.3-41.4) received any NOACs. After adjusting for age, gender, income, insurance status, and stroke risk factors, the odds of receiving any OAC was .69 (95% CI: .58-.83) in blacks, .74 (.53-1.903) in Hispanics, and .75 (.58-.95) in Asians compared to whites. Among anticoagulated patients, blacks and Hispanics had significantly lower odds of receiving NOACs: .72 (.53-.97) and .53 (.29-.99), respectively. Use of NOACs, as compared to VKAs, was associated with significantly lower risk of stroke [.52(.31-.85)] and bleeding [.72(.54-.95)] in whites but not in non-whites [stroke: .71 (.22-2.31); bleeding .83(.43-1.57)] independent of other risk factors. Conclusions: Racial minorities with AF who are at risk of stroke were less likely to receive any OAC and NOACs specifically compared to whites even after accounting for insurance status, income, and stroke risk factors. Independent of other risk factors, use of NOACs as compared to VKA was associated with significantly lower risk of stroke and bleeding only in whites but not in non-whites.

The prognostic utility of ICH-score in anticoagulant related intracerebral hemorrhage

Although intracerebral hemorrhage (ICH) score is used to provide an estimate on the probability of mortality following spontaneous ICH of any cause, its utility has not been exclusively tested in ICH patients with history of treatment with vitamin K antagonists (VKAs) or non-vitamin K oral anticoagulants (NOACs). The aim of the present report is to investigate the utility of ICH score for mortality prognostication of VKA-ICH and NOAC-ICH patients. We used receiver operating characteristic curve analyses to estimate the accuracy parameters for the different values of ICH score in the prognosis of mortality within 30-days after the onset of NOAC-ICH or VKA-ICH.We analyzed data from 108 NOAC-ICH and 241 VKA-ICH patients (median age 76 years, 58% males, median NIHSS score 11 points, median ICH-score 2 points). ICH score of 4 points was uncovered to be the most favorable threshold for the prediction of 30-day mortality both after NOAC-ICH (sensitivity: 57.7%, specificity: 98.8%) or VKA-ICH (sensitivity: 42.1%, specificity: 92.6%). However, comparison of the areas under the curve (AUC) suggested a cumulatively higher (p = .001) predictive value of ICH-score in the prognostication of 30-day mortality after ICH related to the use of NOACs (AUC: 0.92, 95%CI: 0.86–0.98) compared to the ICH related to the use of VKAs (AUC: 0.77, 95%CI: 0.70–0.83). In conclusion, ICH score seems to have an adequate predictive utility in the prognostication of 30-day mortality following an ICH related to the use of oral anticoagulants, with better yield in ICH cases associated with the use of NOACs.

Management and outcomes of real-world use of non-vitamin-K oral anticoagulants (NOACs) in patients with atrial fibrillation: experience of adedicated NOAC clinic.

BackgroundCurrent guidelines recommend non-vitamin‑K oral anticoagulants (NOACs) as the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF). The use of drugs in a clinical trial setting differs from that in real-world populations. Real-world data are important to accrue more heterogeneous patient populations with respect to co-morbidities and co-medication use. The aim of this study was to evaluate the use of NOACs in daily practice in a large tertiary hospital in the Netherlands.MethodsA single-centre prospective study was conducted among all patients with AF using a NOAC in the St. Antonius Hospital between 2013 and June 2017. The outcomes were the rates of any bleeding, stroke/transient ischaemic attack, mortality, discontinuation rate and adverse drug reactions.ResultsIn total, 799 patients were enrolled with a mean follow-up of 1.7 years. Mean age was 69.8 (SD ± 11) and 61.2% were male. Mean CHA2DS2-VASc score was 2.8 (SD ± 1.6) and mean HAS-BLED score was 1.4 (SD ± 0.9). Bleeding occurred in 6.0, major bleeding in 1.8, stroke in 1.2 patients per 100 patient-years, and 87 patients (10.9%) died during the follow-up period. Adverse drug reactions were reported by 59 patients (7.4%). Finally, 249 patients (31.2%) reported a temporary interruption and 132 (16.5%) permanent discontinuation of NOAC treatment, of whom 33 (25%) patients switched to a vitamin‑K antagonist.ConclusionsWe observed low rates of bleeding and adverse drug reactions. However, rates of mortality and discontinuation were relatively high. These results could possibly be explained by the real-world nature of the data including higher-risk patients.Electronic supplementary materialThe online version of this article (10.1007/s12471-019-01330-y) contains supplementary material, which is available to authorized users.

Using non-vitamin K oral anticoagulants in specific patient populations: a study of Korean cases.

Non-vitamin K oral anticoagulants (NOACs) are increasingly used as alternatives to conventional therapies and have considerable accumulated real-world clinical data in patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). However, it is not easy to make a complete changeover to NOACs in real-world clinical practice because NOACs still have challenges in specific patient populations (eg, Asian patients, NVAF patients presenting with acute coronary syndrome [ACS], dialysis patients with NVAF, patients with cancer-associated VTE, etc.). Clinical data on the optimal dose of NOACs in Asian patients with NVAF are not sufficient. The intensity of NOAC and antiplatelet treatment and the duration of antiplatelet treatment should be adjusted according to the bleeding and thrombotic risk profiles of the individual NVAF patient presenting with ACS. Increased bleeding risk and unclear efficacy of NOACs in dialysis patients with NVAF should be considered when making decisions on whether to give NOACs for these patients. If dialysis patients with NVAF require anticoagulant for stroke prevention, then apixaban could be considered while awaiting more clinical efficacy and safety data. Additional studies are needed to determine the utility of continuing treatment with reduced-dose NOACs for long-term therapy after VTE. We have enough experiences in using NOACs in cancer patients showing the benefit of antithrombotic treatment counterbalanced the bleeding risk; however, some challenges of cancer-associated VTE management exist due to differences in cancer types or chemotherapy regimens and comorbidities. Different dosing regimens among NOACs may impact on medication adherence; thus, individual patient preference should be considered in choosing a particular NOAC. A significant proportion of patients remain on warfarin because of the high price of NOACs and variability in reimbursement coverage. To compensate clinical-evidence and achieve optimal use of NOACs, we should pay attention to the outcomes of ongoing studies and evaluate more real-world data.

The Changing Face of Venous Thromboembolism Management in England

Aim: Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, poses a global disease burden. Vitamin K antagonists have traditionally been the mainstay of treatment; however, the non-vitamin K oral anticoagulants (NOACs) are emerging as an alternative. The relative use of these treatment classes in the real world is unknown. Patients & methods: We performed a retrospective study using data from the UK Clinical Practice Research Datalink to understand VTE treatment patterns. Results: NOACs have unseated vitamin K antagonist as the main form of VTE patient treatment in England. Conclusion: The data highlight how comfortable physicians have become in using NOACs to treat VTE in England and it is likely that the increasing use of NOACs will continue.

Acute Lower Gastrointestinal Bleeding in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice: Characteristics and Clinical Outcome.

BackgroundAcute lower gastrointestinal bleeding (ALGIB) can occur in patients on anticoagulant therapy (either warfarin or non-vitamin K oral anticoagulants (NOACs)). Use of NOACs has been increasing compared to warfarin in recent years. We analyzed patients with ALGIB on anticoagulation therapy and compared characteristics, management and clinical outcome in patients treated with NOACs versus warfarin.MethodsAll patients with ALGIB on anticoagulation therapy treated in two (affiliated) centers during a 7-year period were evaluated. Characteristics and clinical outcome were compared between patients on warfarin and patients on NOACs.ResultsOut of the 587 patients identified with ALGIB during the study period, 43 (7.3%) were on NOACs and 68 (11.6%) on warfarin. Mean age was 75.9 ± 9.5 and 77.1 ± 7.9 years respectively. Site of bleeding was located in the small bowel in 2/43 of NOAC patients and 6/68 of warfarin group. Vascular ectasias (8/43 vs. 6/68, P = 0.010) and polyps/neoplasia (13/43 vs. 6/68, P = 0.025) were more commonly causes of bleeding in patients on NOACs. While endoscopic hemostasis was more commonly needed in patients on NOACs (17/43 vs. 14/68, P = 0.049), they required less hospitalization days (4.5 ± 3.6 vs. 6.1 ± 4.2, P = 0.032). Blood transfusions and need for other interventions (embolization and/or surgery) as well as recurrence of bleeding and mortality were not statistically different.ConclusionsAlthough NOAC patients with ALGIB exhibit some differences on certain clinical characteristics when compared to warfarin patients, they share a similar clinical outcome.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

PERSISTENCE OF ORAL ANTICOAGULANT USE AMONG CANADIAN ATRIAL FIBRILLATION PATIENTS: ONE-YEAR RESULTS FROM THE PROSPECTIVE SPRINT-AF REGISTRY

Despite the proven benefit of oral anticoagulation (OAC) in reducing the risk of stroke among atrial fibrillation (AF) patients, there is lingering concern that persistence with these life-saving medications is suboptimal in routine clinical practice. From a prospective registry, we sought to examine: (i) the one-year persistence rates to warfarin and non-vitamin K oral anticoagulants (NOAC) and (ii) factors associated with OAC persistence. We enrolled 2,498 AF patients from 132 community-based sites in Canada (November 2013 to March 2016) in a prospective registry. Use of OAC at one year was ascertained by telephone follow-up. Multivariable logistic regression was performed to examine for factors associated with continued OAC use (vs. non-use) at one-year. Among patients who remained treated with OAC at one-year, a multivariable logistic regression was performed to examine for factors associated with use of the same OAC agent vs. being switched to another OAC agent. Among the 2,010 patients treated with OAC at baseline, one-year data on OAC use were obtained for 1,387 (69%) patients. In this cohort, 124 patients (8.9%) were no longer treated with OAC at one-year. The rates of OAC discontinuation of warfarin- and NOAC-treated patients were 5.1% and 10.5%, respectively (P<0.05). The distribution of OAC use at one-year, stratified by baseline OAC use, was shown in the figure. On multivariable regression analysis, use of NOAC and concomitant use of antiplatelet agents were associated with increased likelihood of OAC discontinuation at one-year (odds ratio (OR) 2.22, 95% CI 1.35-3.70 and OR 2.50, 95% CI 1.54-4.00). Among patients who remained treated with OAC at one-year, the odds of staying on the same OAC agent were higher for patients treated with factor Xa inhibitors when compared to those treated with warfarin at baseline (OR 1.64, 95% CI 1.05-2.54 (rivaroxaban vs. warfarin) and OR 5.26, 95% CI 2.22-12.5 (apixaban vs. warfarin)). Similar results were obtained when our analysis was restricted to patients treated with the same OAC for >90 days prior to their baseline visit. In this contemporary Canadian AF registry, the one-year persistence rates of OAC were high irrespective of the type of agent prescribed. Among patients who experienced a change in their OAC use, warfarin-treated patients were more likely to switch to NOACs instead of stopping OAC. NOAC-treated patients were more likely to discontinue use of OAC altogether rather than being switched to warfarin.

Economic evaluation of the use of non-vitamin K oral anticoagulants in patients with atrial fibrillation on antiplatelet therapy: a modelling analysis using the healthcare system in the Netherlands.

Non-vitamin K oral anticoagulants (NOACs) have consistently demonstrated superior efficacy in terms of stroke prevention and safety in terms of bleeding over vitamin K antagonist (VKA) in patients with non-valvular atrial fibrillation (AF). The potential use of NOACs in AF patients requiring antiplatelet therapy (APT) has only been assessed in small meta-analyses reporting consistent benefits of NOACs over VKAs. However, the prescription costs of NOACs are higher than those of VKAs. The aim of his study was to estimate the cost-effectiveness (CE) of NOACs compared to VKAs in patients with non-valvular AF also requiring APT with the Dutch healthcare system used as a surrogate of many European healthcare systems. A decision tree was constructed to analyse the CE of NOACs compared to VKAs in patients with non-valvular AF with an indication for APT over a horizon of 1 year. Beside the base-case analysis, univariate probabilistic sensitivity and two sensitivity analyses were performed: first, we assessed the impact of VKA home monitoring; second, we varied the NOACs price assuming patent expiration. Use of NOACs instead of VKA is associated with a health gain of 0.0171 quality-adjusted life years (QALYs) and with an incremental cost of €357, resulting in an incremental cost-effectiveness ratio of €20919, which is almost equal to the generally accepted CE threshold of €20000 used in the Netherlands. The probability that NOACs are cost-effective at a conservative willingness-to-pay threshold of €20000 per QALY was 50%. Introducing home monitoring increased VKAs costs so much that NOACs became the dominant option (less costly and more effective). Price drops associated to patent expiration of NOACs increased its CE. This analysis suggests that the use of NOACs is a cost-effective alternative of VKAs in patients with AF needing APT. Our findings in the Netherlands healthcare system are probably consistent with other European populations.

Secondary adherence to non-vitamin-K antagonist oral anticoagulants in patients with atrial fibrillation in Sweden and the Netherlands

Objective: There is limited evidence on patients’ adherence and the impact of the prescribed dosing regimen in non-vitamin-K oral anticoagulants (NOACs). We aimed to assess secondary adherence to NOACs and to determine the impact of the dosing regimen in patients with atrial fibrillation.Methods: Patients using a NOAC between 2009 and 2013 were identified from the nation-wide Swedish Prescribed Drug Register and the Dutch regional IADB.nl database. Patients using a consistent dosage for at least 180 consecutive days were included. Adherence was calculated using the medication possession ratio (MPR) and adjusted for overlapping dates. Adherence was defined as a MPR ≥0.8. Sensitivity analyses were performed using a MPR ≥0.9. Logistic regression was performed to compare secondary adherence and to explore the influence of the dosing regimen.Results: A total of 5254 Swedish and 430 Dutch NOAC users were included. The mean MPR was 96.0% (SD 7.8%) in Sweden and 95.1% (SD 10.1%) in the Netherlands. Multivariable logistic regression analysis showed that a twice daily regimen had a lower likelihood of being secondary adherent compared to a once daily regimen in Sweden (odds ratio [OR] 0.21 [95% CI 0.12–0.35]).Limitations: The influence of selection bias introduced by the inclusion criterion of ≥2 dispensations covering at least 180 days could not be excluded.Conclusions: This study demonstrated that secondary adherence was high in this specific setting among patients with at least two initial dispensations of a NOAC covering a minimum of 180 days. The use of NOACs in a once daily regimen showed higher adherence compared to a twice daily regimen.