Non-vitamin K Antagonist Oral Anticoagulants Users Research Articles

Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds

ObjectiveTo evaluate if proton pump inhibitor (PPI) treatment reduces the risk of upper gastrointestinal bleeding (UGIB) in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs).DesignWe...

Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries

AimsTo assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings.Methods and resultsWe conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only.ResultsOverall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up.ConclusionPersistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban.

Assessment of non-vitamin K antagonist oral anticoagulants for the management of left ventricular thrombus.

Although several studies have assessed the effect of non‐vitamin K antagonist oral anticoagulants (NOACs) relative to that of vitamin K antagonists (VKAs) in patients with left ventricular thrombus, the results remain controversial. Herein, a meta‐analysis was performed to compare the effectiveness and safety of NOACs versus VKAs for the treatment of left ventricular thrombus. We systematically searched the Cochrane Library, PubMed and Embase databases until November 2020 for studies that compared the effects of NOACs versus VKAs in patients with left ventricular thrombus. The treatment effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) and pooled by a random‐effects model. Seven retrospective studies involving 865 patients with left ventricular thrombus (266 NOAC and 599 VKA users) were included. The pooled analysis suggested no difference in the rate of thrombus resolution between the NOAC and VKA groups (OR = 0.83, 95% CI 0.61–1.13). There were also no differences in the rates of stroke or systemic embolism (OR = 0.62, 95% CI 0.20–1.97), bleeding events (OR = 0.73, 95% CI 0.37–1.45), or all‐cause death (OR = 0.92, 95% CI 0.50–1.69) between patients treated with NOACs and those treated with VKAs. In addition, the rates of thrombus resolution, stroke or systemic embolism, bleeding events, and all‐cause death between NOAC‐ and warfarin‐treated patients were also similar. Our current evidence suggested that NOAC and VKA users had similar rates of thrombus resolution and clinical outcomes among patients with left ventricular thrombus. Further large‐scale prospective studies should confirm our results.

Patient characteristics, adherence, and costs of oral anticoagulation therapy in non-valvular atrial fibrillation using the Dubai Real-World Claims Database

ABSTRACTBackground:Non-vitamin K antagonist oral anticoagulants (NOACs) reduce the risk of stroke in patients with non-valvular atrial fibrillation (NVAF) and have better safety profile than vitamin K antagonists (VKAs). However, there is a dearth of quality, real-world, patient data on the use of these drugs to guide healthcare policies in United Arab Emirates (UAE).Aims and Objectives:The aim is to address the knowledge gap in demographic and clinical profiles of NVAF patients on NOACs (apixaban, rivaroxaban, and dabigatran) and warfarin in UAE.Materials and Methods:This retrospective cohort analysis utilized the Dubai Real-World Claims Database to extract anonymized longitudinal data on NVAF patients with at least one NOAC or warfarin claim between January 2015 and March 2019. Data examined included comorbidities, healthcare resource utilization (HCRU), treatment adherence, and clinical events.Results:From 11,086 NVAF patients in the database, 940 patients on oral anticoagulant treatment were selected with mean age of 58.6 ± 14.7 years and 73.7% men. At baseline, the mean CHA2DS2-VASc risk score was 2.4, and the mean Deyo–Charlson comorbidity index (CCI) score was 1.6. Most patients (71%) started oral anticoagulation treatment on a standard index dose. High medication possession ratio (MPR) and proportion of days covered (PDC) were observed in 86.8% and 43.1% of the overall cohort. The mean number of HCRU claims and cost during the 180-day follow-up period was 18.5 and 9,747 USD, respectively. Warfarin users accounted for both the highest number of claims and cost, whereas apixaban accounted for the lowest figures. Time to first major bleeding was shorter for warfarin users compared with patients on NOACs. Longer times to first stroke/systemic embolism (SE) were observed for rivaroxaban and warfarin.Conclusion:This study provides important comparative insights about comorbidities, adherence, HCRU, and outcome events among NOAC and warfarin users from real-world clinical practice settings.

Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta-Analysis.

BackgroundEvidence on the differences in fracture risk associated with non‐vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta‐analysis to assess the fracture risk associated with NOACs and warfarin.Methods and ResultsWe searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random‐effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77–0.91; P<0.001) with low heterogeneity (I 2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81–0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54–1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real‐world cohort studies were quite consistent, indicating the robustness of our findings.ConclusionsCompared with warfarin, NOACs are associated with lower risks of bone fracture.

ANTICOAGULATION BEFORE AND AFTER CARDIOVERSION OR ABLATION. CHALLENGES, PROBLEMS AND MISTAKES

Background: Limited data exists addressing the daily use of anticoagulants for atrial fibrillation (AF) and atrial flutter (AFL) patients before and after electrical cardioversion (ECV) or catheter ablation procedures. The purpose of the study was to evaluate the appropriateness of anticoagulant therapy. Methods: We evaluated the prescribed dosage of anticoagulant therapy for 257 non-valvular AF and AFL patients scheduled for ECV or catheter ablation and the appropriateness of periprocedural anticoagulation according to European Society of Cardiology (ESC) AF Guidelines. The statistical analysis was performed using IBM SPSS Statistics software (v.26.0). Results: The majority of the patients (84%) used nonvitamin K antagonist oral anticoagulants (NOACs) for pre-procedural anticoagulation. An intervention was not performed for 12.2% of warfarin users because of insufficient hypocoagulation, while anamnesis of patients’ missed doses with a possibility of inadequate hypocoagulation occurred only in 1.9% of patients on NOACs. The odds of having insufficient pre-procedural hypocoagulation were 7.4 times higher for warfarin users compared to the NOACs group (p=0.001, OR=7.4). An incorrect NOAC dose was assigned to 22 (8.6%) patients. Rivaroxaban was the most prescribed NOAC and this group of patients had the highest percentage of incorrect dosage according to the ESC guidelines. Conclusions: Mistakes of prescribing the dosage of anticoagulant therapy are common. The majority of the patients in the study were prescribed with NOACs before and after ECV or catheter ablation procedures. Warfarin users had higher odds of the intervention not being performed and not reaching sufficient hypocoagulation prior to the procedure compared to NOACs users.

The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis.

ObjectiveOur study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin.MethodsWe searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893).ResultsWe included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81–1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82–1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80–0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76–0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin.ConclusionThe meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

Adherence to oral anticoagulation in ischemic stroke patients with atrial fibrillation

Background Non-vitamin K antagonist oral anticoagulants (NOAC) have superior safety and comparable efficacy profile compared to vitamin-K antagonists (VKAs), with more convenient dosing schemes. However, issues with adherence to the NOACs remain unsolved. Aims We sought to investigate the adherence to oral anticoagulation (OAC) and baseline factors associated with poor adherence after ischaemic stroke in patients with atrial fibrillation (AF). Methods We recruited hospitalised patients (2013–2019) from two prospective stroke registries in Larissa and Helsinki University Hospitals and invited survived patients to participate in a telephone interview. We assessed adherence with the Adherence to Refills and Medications Scale (ARMS) and defined poor adherence as a score of over 17. In addition to demographics, individual comorbidities, and stroke features, we assessed the association of CHA2DS2-VASc and SAMe-TT2R2 scores with poor adherence. Results Among 396 patients (median age 75.0 years, interquartile range [IQR] 70–80; 57% men; median time from ischaemic stroke to interview 21 months [IQR 12–33]; median ARMS score 17 [IQR 17–19]), 56% of warfarin users and 44% of NOAC users reported poor adherence. In the multivariable regression model adjusted for site, sex, and age, poor adherence was independently associated with tertiary education, absence of heart failure, smoking history, use of VKA prior to index stroke, and prior ischaemic stroke. CHA2DS2-VASc and SAMe-TT2R2 scores were not associated with poor adherence. Conclusions Adherence was poor in half of AF patients who survived an ischaemic stroke. Independent patient-related factors, rather than composite scores, were associated with poor adherence in these patients. KEY MESSAGES Adherence was poor in half of the atrial fibrillation patients who survived an ischaemic stroke. Independent patient-related factors rather than composite scores were associated with poor adherence. The findings support the importance of recognising adherence support as a crucial part of holistic patient care recommended by recent AF guideline.

Prevalence of drug-drug interactions for oral anticoagulant drugs in patients with atrial fibrillation and relationship with outcomes: a population-based cohort study

Abstract Introduction The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) changed the treatment of atrial fibrillation (AF) patients, promising a better safety profile and a lower chance of interaction with drugs than vitamin K antagoniste (VKA). Aim To evaluate the prevalence of possible drug-drug interactions (DDIs) in a cohort of newly anticoagulated AF patients, their impact on outcomes and possible differences between VKA and NOACs users. Methods We performed an analysis derived from administrative databases in Lombardy Italian region. All patients ≥40 years admitted from 01/06/2013 to 30/06/2018 with an AF diagnosis that were VKA or NOACs new users were included in this analysis. Possible DDIs were evaluated according to the prescription of OAC therapy, on the basis of current available evidence. Stroke, intracerebral hemorrhage (ICH), any bleeding and all-cause death were the study outcomes. Results Among the 122816 patients included in the analysis, mean (SD) age 76.3 (9.6) with 47.3% females, a mean (SD) CHA2DS2-VASc of 3.5 (1.4) was found. A total of 70180 (57.1%) patients were prescribed with VKA and 52636 (42.9%) with NOACs. A possible DDI was recorded in 63273 (51.5%). Patients exposed to DDIs were older and less likely female (both p&amp;lt;0.0001) and with a higher mean (SD) CHA2DS2-VASc (p&amp;lt;0.0001). Rate of stroke, ICH, any bleeding and all-cause death were higher in those patients exposed to DDIs (all p&amp;lt;0.001). After full adjustment, exposure to possible DDIs was associated with an increased risk for any bleeding (HR: 1.08, 95% CI: 1.05–1.12) and all-cause death (HR: 1.10, 95% CI: 1.07–1.13), with no differences for stroke and ICH. Comparing VKA and NOACs patients exposed to possible DDIs, we found that VKA users exposed to possible DDIs, after adjustments, were at higher risk for all the outcomes (Table). Conclusions In a large cohort of AF patients newly prescribed with OAC, possible DDIs were largely prevalent, in particular in VKA users. Presence of a possible DDI is associated with an increased risk of any bleeding and all-cause death. VKA users exposed to a possible DDI were at higher risk for any outcome than NOACs users exposed to a possible DDI. Funding Acknowledgement Type of funding source: None

Association of anticoagulant therapy with risk of dementia among patients with atrial fibrillation.

To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs). This observational, population-based cohort study enrolled 53236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74-0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC. In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.

Cardiovascular risks and bleeding with non-vitamin K antagonist oral anticoagulant versus warfarin in patients with type 2 diabetes: a tapered matching cohort study

BackgroundWe compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM).Methods862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017–30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i–vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i–vi.ResultsThe 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97–3.84), 2.14 (1.03–4.44), 2.31 (1.10–4.85), 2.42 (1.14–5.14), 2.41 (1.12–5.18), and 2.51 (1.17–5.38) through steps i–vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i–vi: 2.21 (1.04–4.68), 2.13 (1.01–4.52), 2.47 (1.08–5.62), 2.46 (1.02–5.94), 2.51 (1.01–6.20), and 2.66 (1.02–6.94).ConclusionsIncident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted.

Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant

Aims We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin-K antagonist oral anticoagulant (NOAC) therapy. Methods This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis. Results Overall rate of minor bleeds was 19.2 per 100 patient years of follow-up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use). Limitation This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting. Conclusion Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding.

Community pharmacy-based study of adherence to non-vitamin K antagonist oral anticoagulants

ObjectiveThis study aimed to assess implementation adherence (how well the patient’s actual intake matches the prescribed dosing regimen) to non-vitamin K antagonist oral anticoagulants (NOACs) and to explore experiences with...

Association Between Nonvitamin K Antagonist Oral Anticoagulants or Warfarin and Liver Injury: A Cohort Study.

The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, and apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests. Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010 and 2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities, and medications by propensity score on a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression. After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% confidence interval: 0.58-0.89). When comparing individual NOACs, only dabigatran (hazard ratio: 0.63; 95% confidence interval: 0.48-0.82) was associated with a lower risk of liver injury. Among patients with AF, NOACs as a group, and dabigatran alone were associated with a significantly lower risk of laboratory-based liver injury when compared with warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials.

Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study

We investigated the prevalence of retinal vascular occlusion and intraocular bleeding and compare their risks in patients undergoing anticoagulant therapy, either with non-vitamin K-antagonist oral anticoagulants (NOAC) or warfarin. We performed a cohort study (January 2015 to April 2018) in 281,970 patients with nonvalvular atrial fibrillation (AF) using health claims in the nationwide database of the Health Insurance Review and Assessment service of Korea. A Cox-proportional hazard regression was used to calculate the hazard ratio (HR) for retinal vascular occlusion or intraocular bleeding. The HR of retinal vascular occlusion was estimated to 1.59 (95% confidence interval [CI], 1.35–1.86) for NOAC users compared to that with warfarin users. Among the various types of NOACs, all NOACs showed higher risk of retinal vascular occlusion than did warfarin. For intraocular bleeding, the HR was estimated to be 0.86 (95% CI, 0.75–0.98) for NOAC users compared with that with warfarin users. The risk of retinal vascular occlusion was higher in NOAC users than in warfarin users, while the risk of intraocular bleeding was lower with NOAC therapy. NOACs were not found to be as effective as warfarin for retinal vascular occlusion, but safe in terms of intraocular bleeding.

Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study

AimsThe aim of this study was to compare the risk of stroke or systemic embolism (SE) and major bleeding in patients with atrial fibrillation (AF) using dabigatran, rivaroxaban, and apixaban in routine clinical practice.Methods and resultsUsing nationwide registries in Norway from January 2013 to December 2017, we established a cohort of 52 476 new users of non-vitamin K antagonist oral anticoagulants (NOACs) with AF. Users of individual NOACs were matched 1:1 on the propensity score to create three pairwise-matched cohorts: dabigatran vs. rivaroxaban (20 504 patients), dabigatran vs. apixaban (20 826 patients), and rivaroxaban vs. apixaban (27 398 patients). Hazard ratios (HRs) for the risk of stroke or SE and major bleeding were estimated. In the propensity-matched comparisons of the risk of stroke or SE, the HRs were 0.88 [95% confidence interval (CI) 0.76–1.02] for dabigatran vs. rivaroxaban, 0.88 (95% CI 0.75–1.02) for dabigatran vs. apixaban, and 1.00 (95% CI 0.89–1.14) for apixaban vs. rivaroxaban. For the risk of major bleeding, the HRs were 0.75 (95% CI 0.64–0.88) for dabigatran vs. rivaroxaban, 1.03 (95% CI 0.85–1.24) for dabigatran vs. apixaban, and 0.79 (95% CI 0.68–0.91) for apixaban vs. rivaroxaban.ConclusionIn this nationwide study of patients with AF in Norway, we found no statistically significant differences in risk of stroke or SE in propensity-matched comparisons between dabigatran, rivaroxaban, and apixaban. However, dabigatran and apixaban were both associated with significantly lower risk of major bleeding compared with rivaroxaban.

Concomitant Use of NSAIDs or SSRIs with NOACs Requires Monitoring for Bleeding.

PurposeNon-vitamin K antagonist oral anticoagulants (NOACs) are widely used in patients with atrial fibrillation (AF) because of their effectiveness in preventing stroke and their better safety, compared with warfarin. However, there are concerns for an increased risk of bleeding associated with concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs) with NOACs. In this study, we aimed to evaluate the risk of bleeding events in individuals taking concomitant NSAIDs or SSRIs with NOACs after being diagnosed with AF.Materials and MethodsA nested case-control analysis to assess the safety of NSAIDs and SSRIs among NOAC users with AF was performed using data from Korean National Health Insurance Service from January 2012 to December 2017. Among patients who were newly prescribed NOACs, 1233 cases hospitalized for bleeding events were selected, and 24660 controls were determined.ResultsThe risk of bleeding events was higher in patients receiving concomitant NSAIDs [adjusted odds ratio (aOR) 1.41; 95% confidence interval (CI) 1.24–1.61] or SSRIs (aOR 1.92; 95% CI 1.52–2.42) with NOACs, compared to no use of either drug, respectively. The risk of upper gastrointestinal bleeding was higher in patients receiving concomitant NSAIDs or SSRIs without proton pump inhibitors (PPIs) (NSAIDs: aOR 2.47; 95% CI 1.26–4.83, SSRI: aOR 10.8; 95% CI 2.41–2.48) compared to no use.ConclusionWhen NSAIDs or SSRIs are required for NOAC users with AF, physicians need to monitor bleeding events and consider the use of PPIs, especially for combined use of both drugs or when initiating NOACs treatment.

Real-world comparisons of reduced-dose non-vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation: a systematic review and meta-analysis.

We performed this meta-analysis to compare the efficacy and safety of reduced-dose non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF). The PubMed and Embase databases were systematically searched until July 2019 for eligible studies that comparing the effect between any reduced-dose NOAC and warfarin in patients with AF. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled by using a random-effects model. A total of 14 observational cohorts were included. Compared with warfarin use, the use of reduced-dose NOACs was associated with decreased risks of stroke or systemic embolism (RR, 0.83; 95% CI 0.74-0.93), ischemic stroke (RR, 0.87; 95% CI 0.77-0.98), major bleeding (RR, 0.71; 95% CI 0.60-0.84), intracranial hemorrhage (RR, 0.51; 95% CI 0.44-0.60), and gastrointestinal bleeding (RR, 0.72; 95% CI 0.54-0.94), but not all cause death (RR, 0.84; 95% CI 0.67-1.06). In the subgroup analyses, all NOAC users had lower or similar rates of thromboembolic and bleeding events; and the reductions in stroke or systemic embolism, all-cause death, major bleeding, and gastrointestinal bleeding were more prominent in Asians than non-Asians. In conclusion, current published data suggest that the use of reduced-dose NOACs is non-inferior to warfarin in patients with AF (in particular Asians).

The optimal drug adherence to maximize the efficacy and safety of non-vitamin K antagonist oral anticoagulant in real-world atrial fibrillation patients.

To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Using the Korean National Health Insurance Service database, we identified 96197 patients with non-valvular AF who initiated NOAC or warfarin in 2013-16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69-0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72-0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91-1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93-1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03-1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.

64Risk of dementia in patients treated with non-vitamin k antagonist oral anticoagulant or warfarin for nonvalvular atrial fibrillation

Abstract Background Evidence is accumulating that use of oral anticoagulants (OACs) decreases the risk of dementia in patients with atrial fibrillation (AF), but it is unclear if there is a difference between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in protecting against dementia. Purpose To compare the risk of dementia between patients taking either NOAC or warfarin using a nationwide cohort data covering the entire Korean population. Methods Using the Korean national health insurance service database, 68,984 new OAC users with non-valvular AF aged ≥50 years and no prior diagnosis of dementia were identified during the period of 2013–2016 (39,687 NOAC users and 29,297 warfarin users). Starting from OAC initiation, participants were followed up until the date of dementia, death, or December 31, 2016. We compared the rates of dementia in 1:1 propensity score-matched cohorts of NOAC (n=18,925) and warfarin users (n=18,925). Results During the 52,259 person-years of follow-up, there were 2,750 dementia events. Use of NOAC was associated with significant lower risk of dementia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.69–0.81], compared with warfarin. The risk reduction was prominent for vascular dementia (HR 0.60, 95% CI 0.52–0.71), whereas there was no significant difference in the risk of Alzheimer dementia (HR 0.92, 95% CI 0.83–1.02). Restricting the analyses to patients with no stroke diagnosis prior to OAC initiation (primary prevention) showed no significant difference between NOAC and warfarin in any types of dementia, but in the subgroup with prior stroke (secondary prevention), NOAC significantly reduced the risk of overall (HR 0.70, 95% CI 0.63–0.78) and vascular dementia (HR 0.59, 95% CI 0.49–0.69). Subgroup analysis according to stroke Hx Patient N Overall dementia Alzheimer dementia Vascular dementia HR (95% CI) P for interaction HR (95% CI) P for interaction HR (95% CI) P for interaction Total 37,850 0.75 (0.69–0.81) 0.92 (0.83–1.02) 0.60 (0.52–0.71) Without prior stroke 24,773 0.90 (0.78–1.05) 0.948 0.98 (0.83–1.15) 0.235 0.85 (0.56–1.28) 0.863 With prior stroke 13,077 0.70 (0.63–0.78) 0.90 (0.79–1.03) 0.59 (0.49–0.69) CI, confidence interval; HR, hazard ratio. KM curves of dementia incidence Conclusion In this propensity-weighted nationwide cohort of non-valvular AF patients, NOAC was associated with reduced risk of dementia, compared with warfarin. This association was the most pronounced for vascular dementia in patients with prior stroke. Acknowledgement/Funding The Korean Ministry of Education, Science and Technology (NRF-2017R1A2B3003303) and the Korean Ministry of Health &amp; Welfare (HI16C0058, HI15C1200)