Clinical implications of combination proton pump inhibitor and triple therapies in patients with atrial fibrillation following percutaneous intervention: a guide for clinicians.

INTRODUCTION: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. AREAS COVERED: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. EXPERT OPINION: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

Design, Rationale and Initial Findings From HERA-FIB on 10 222 Patients With Atrial Fibrillation Presenting to an Emergency Department Over An 11-Year Period.

BACKGROUND: For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. METHODS AND RESULTS: HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all-cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. CONCLUSIONS: HERA-FIB is one of the largest real-world single-center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non-vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Treatment of Persistent Left Atrial Appendage Thrombus in Patients with Atrial Fibrillation on Adequate Oral Anticoagulation: Pathways of Care for All-comers and Heart Failure Patients.

In patients with AF, the presence of left atrial/left atrial appendage (LA/LAA) thrombus is related to an increased risk of thromboembolic events. Anticoagulation therapy, either with vitamin K antagonists or novel oral anticoagulants (NOACs) is therefore mandatory in AF with LA/LAA thrombus in order to lower the risk of stroke or other systemic embolic events. Despite the efficacy of these treatments, some patients will have persistent LAA thrombus remaining or may have contraindications to oral anticoagulation. Currently, little is known about the occurrence, risk factors and resolution rate of LA/LAA thrombus in patients who are already under optimal chronic oral anticoagulation, including vitamin K antagonists or NOACs. The common action in clinical practice in this scenario is switching from one to another anticoagulant drug exhibiting a different mechanism of action. Repeated cardiac imaging is then advised within several weeks to visually verify thrombus dissolution. Finally, there is a substantial scarcity of data on the role and optimal use of NOACs after LAA occlusion. The aim of this review is to critically evaluate data and provide up-to-date information on the best antithrombotic strategies in this challenging clinical scenario.

Atraumatic Splenic Rupture: A Notable Complication of Rivaroxaban Use.

Direct oral anticoagulants (DOACs) are well known to be associated with bleeding complications. However, little is known about their association with atraumatic splenic rupture, a potentially fatal condition. We present the case of a 73-year-old female with paroxysmal atrial fibrillation managed with rivaroxaban who developed a spontaneous atraumatic splenic rupture. This highlights the importance of recognizing this complication in patients without previous risk factors, such as abdominal trauma or infiltrative splenic disease, who are under anticoagulation with DOACs. There is a strong need for further research on this complication's underlying mechanism and management.

Contemporary trends and barriers to oral anticoagulation therapy in Non-valvular atrial fibrillation during DOAC predominant era.

There is a need to reassess contemporary oral anticoagulation (OAC) trends and barriers against guideline directed therapy in the United States. Most previous studies were performed before major guideline changes recommended direct oral anticoagulant (DOAC) use over warfarin or have otherwise lacked patient level data. Data on overuse of OAC in low-risk group is also limited. To address these knowledge gaps, we performed a nationwide analysis to analyze current trends. This is a retrospective cohort study assessing non-valvular AF identified using a large United States de-identified administrative claims database, including commercial and Medicare Advantage enrollees. Prescription fills were assessed within a 90-day follow-up from the patient's index AF encounter between January 1, 2016, and December 31, 2020. Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, moderate-, and high-risk groups (according to CHA2DS2-VASc score). An over (29.6%) and under (52.2%) utilization of OAC was reported in low- and high-risk AF patients. A considerably high frequency for warfarin use was also noted among high-risk group patients taking OAC (33.1%). The results suggest that anticoagulation use for stroke prevention in the United States is still comparable to the pre-DOAC era studies. About half of newly diagnosed high-risk non-valvular AF patients remain unprotected against stroke risk. Several predictors of OAC and DOAC use were also identified. Our findings may identify a population at risk of complications due to under- or over-treatment and highlight the need for future quality improvement efforts.

Recurrent Nonbacterial Thrombotic Endocarditis and Primary Antiphospholipid Antibody Syndrome.

In 2015, a 37-year-old man was referred for evaluation of hypertension and was found to have a mobile structure on the posterior mitral valve leaflet on echocardiography. Laboratory investigations yielded a diagnosis of primary antiphospholipid antibody syndrome (APLS). He underwent excision of the lesion and mitral valve repair. Histology confirmed the diagnosis of nonbacterial thrombotic endocarditis (NBTE). The patient was anticoagulated with warfarin up until 2018, which was substituted for rivaroxaban because of an erratic international normalised ratio. Serial echocardiography up to 2020 was unremarkable. In 2021, he presented with breathlessness and peripheral oedema. Echocardiography demonstrated large vegetation on both mitral valve leaflets. At the operation, vegetations were also evident on the left and noncoronary cusps of the aortic valve and he underwent mechanical aortic and mitral valve replacement. Histology confirmed NBTE. The case is unusual and highlights recurrent NBTE requiring re-do valve surgery.

Safety of a single bolus administration of heparin without the measurement of activated clotting time during cryoballoon ablation: a prospective randomized controlled trial.

BACKGROUND: Single-shot ablation has emerged as an effective technique for index atrial fibrillation (AF) ablation, with an advantage of short procedure time. Although recent guidelines recommend peri-procedural uninterrupted oral anticoagulants (OACs), the intra-procedural anticoagulation strategy remains uncertain under non-vitamin K OACs (NOACs). We investigated procedural safety of a single bolus administration of heparin without activated clotting time (ACT) measurement during cryoballoon ablation (CBA). METHODS: Two hundred patients (64.2 ± 10.0 years, 70% with non-paroxysmal AF) who underwent CBA with uninterrupted NOACs were randomly assigned to No-ACT group and ACT group. A bolus of heparin (100 U/kg) was routinely administered immediately after transseptal puncture. In the ACT group, an additional injection of heparin (30 U/kg) was administered if ACT at 30 min after the initial bolus was < 300 s. RESULTS: There were no differences in baseline characteristics including CHA2DS2-VASc score between the two groups. The left atrium indwelling and procedure times were 60.4 ± 13.1 min and 78.9 ± 13.9 min, respectively, and not significantly different between the two groups. The mean ACT was 335.2 ± 59.9 s in the ACT group. Any bleeding rate was 3.2% in all patients and there was no statistically significant difference in bleeding complications between the two groups. In the ACT group, groin hematoma, laryngopharyngeal bleeding, and hemoptysis occurred in 3, 1, and 1 patient, respectively. Cardiac tamponade occurred in 1 patient in the No-ACT group. No thromboembolic events occurred during the 30-day follow-up after CBA. CONCLUSIONS: Single bolus administration of heparin without ACT measurement is a feasible anticoagulation strategy for CBA in patients with uninterrupted NOAC intake.

Patient factors associated with receiving reversal therapy in oral anticoagulant-related intracerebral hemorrhage.

BACKGROUND: We aimed to describe baseline characteristics of patients with oral anticoagulant-related intracerebral hemorrhage (OAC-ICH) in Sweden and to identify predictive variables associated with receiving hemostatic treatment in the event of OAC-ICH. METHODS: We performed an observational study based on data from Riksstroke and the Swedish Causes of Death Register to define baseline characteristics of patients with OAC-ICH who received reversal treatment compared with patients who did not receive reversal treatment during 2017-2019. Predictive analysis was performed using multivariable logistic regression to identify odds ratios for factors associated with receiving OAC reversal treatment. RESULTS: We included 1902 patients ((n = 1146; OAC reversal treatment) (n = 756; no OAC reversal treatment)). The proportion of non-Vitamin K oral anticoagulant associated ICH (NOAC-ICH) patients who received reversal treatment was 48.4% and the proportion of Vitamin K antagonist-associated ICH (VKA-ICH) patients was 72.9%. Factors associated with a lower odds of receiving reversal treatment were increased age (OR = 0.98; 95% CI: 0.96-0.99), previous stroke (OR = 0.78; 95% CI: 0.62-0.98), comatose LOC (OR = 0.36;95%CI: 0.27-0.48; ref. = alert), pre-stroke dependency (OR = 0.72; 95% CI: 0.58-0.91), and NOAC treatment (OR = 0.34; 95% CI: 0.28-0.42). Care at a university hospital was not associated with higher odds of receiving reversal treatment compared to treatment at a county hospital. CONCLUSION: Treatment with a reversal agent following OAC-ICH was related to several patient factors including type of OAC drug. We identified that only 48% of patients with NOAC-ICH received hemostatic treatment despite an increase in these cases. Further studies are required to guide the use of reversal therapies more precisely, particularly in NOAC-ICH.

Edoxaban for stroke prevention in atrial fibrillation and age-adjusted predictors of clinical outcomes in routine clinical care.

AIMS: Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes. METHODS AND RESULTS: The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P < 0.0001). Low kidney function at baseline was the strongest predictor of major bleeding (Wald χ2: 30.68; P < 0.0001). History of heart failure (HF) was the strongest predictor of all-cause (Wald χ2: 146.99; P < 0.0001) and cardiovascular death (Wald χ2: 100.38; P < 0.0001). CONCLUSION: Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively.

Major Bleeding Risk in Atrial Fibrillation Patients Co-Medicated With Non-Vitamin K Oral Anticoagulants and Antipsychotics.

Major bleeding risks associated with non-vitamin K oral anticoagulants (NOACs) used with and without concurrent antipsychotics in patients with non-valvular atrial fibrillation (AF) were assessed. A total of 98,863 patients with non-valvular AF receiving at least one NOAC prescription from Taiwan's National Health Insurance database were enrolled. Major bleeding was defined as a primary diagnosis of intracranial or gastrointestinal hemorrhage or bleeding at other sites. The adjusted incidence rate difference (AIRD) per 1,000 person-years and adjusted rate ratio of major bleeding were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. A total of 8,037 major bleeding events occurred during 705,521 person-quarters with NOAC prescriptions. Antipsychotics were used in 26.35% of NOAC-exposed patients. Compared to using NOAC alone, co-medication of either typical (AIRD: 79.18, 95% confidence interval [CI]: 70.63-87.72) or atypical (AIRD: 40.5, 95% CI: 33.64-47.35) antipsychotic with NOAC had a significant increase in the adjusted incidence rate per 1,000 person-years of major bleeding. The concomitant use of a NOAC with chlorpromazine (AIRD: 103.87, 95% CI: 51.22-156.52), haloperidol (AIRD: 149.52, 95% CI: 125.03-174.00), prochlorperazine (AIRD: 90.43, 95% CI: 78.55-102.32), quetiapine (AIRD: 44.6, 95% CI: 37.11-52.09), or risperidone (AIRD: 41.55, 95% CI: 22.86-60.24) (All p < 0.01) showed a higher adjusted incidence rate of major bleeding than using NOACs alone. The concomitant use of typical (chlorpromazine, haloperidol, or prochlorperazine) or atypical (quetiapine or risperidone) antipsychotic with NOACs was associated with a significantly increased risk of major bleeding.

Non-Vitamin K Oral Anticoagulant After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

Objective: We aimed to compare non-vitamin K oral anticoagulants (NOACs) with a traditional antithrombotic such as vitamin K antagonist (VKA) and antiplatelet agents in patients after transcatheter aortic valve replacement (TAVR). Methods: We conducted a search in PubMed, EMBASE, and the Cochrane Library until November 2021 for studies involving comparisons of any type of NOACs, including dabigatran, apixaban, rivaroxaban, and edoxaban, with VKA or antiplatelet agents after TAVR. A comparison of NOACs versus VKA was performed in patients with an indication for oral anticoagulation. In addition, we compared NOACs versus antiplatelet in patients without such indication. We calculated the hazard ratios with 95% confidence intervals (CIs) to determine long-term outcomes. The primary outcome was a combined endpoint consisting of all-cause mortality, stroke, major bleeding, or any related clinical adverse events. Secondary outcomes were all-cause mortality, major bleeding, and stroke, respectively. Results: A total of 10 studies including 10,563 patients after TAVR were included in this meta-analysis. There were no significant differences in any of the long-term outcomes between the NOAC and VKA groups. Although there were no significant differences in the combined endpoint, major bleeding, or stroke, a significant difference was observed in the all-cause mortality (HR 1.74, 95% CI 1.25-2.43, p = 0.001) between the NOAC and antiplatelet groups. Conclusion: For patients with an indication for oral anticoagulation after TAVR, NOACs seem to be associated with noninferior outcomes compared with VKA therapy. However, for patients without an indication for oral anticoagulation, NOACs appear to be associated with a higher risk of all-cause death as compared with antiplatelet treatment. Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020155122.

Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. METHODS: We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). RESULTS: Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). CONCLUSIONS: The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

Non-Vitamin K Antagonists Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with atrial fibrillation and bioprosthetic valves are at high risk for thromboembolic events. The pooled efficacy and safety of non-vitamin K oral anticoagulants (NOACs), as a class, relative to warfarin in this population is not well-known. We aimed to compare the efficacy and safety of NOACs relative to warfarin in patients with bioprosthetic valves or valve repair. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials comparing NOACs to warfarin in patients with atrial fibrillation and bioprosthetic valves or valve repair. We pooled outcomes for stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, and major bleeding. RESULTS: We included 4 trials with 1379 patients, of whom 723 (52.4%) received a NOAC. Mean follow-up ranged from 90 days to 2.8 years. In the pooled analysis, stroke or systemic embolism was significantly lower in patients treated with NOACs (1.9%) compared with warfarin (3.7%) (odds ratio [OR] 0.43; 95% confidence interval [CI] 0.22-0.85; P = .02). Ischemic stroke (OR 0.72; 95% CI 0.18-2.93), hemorrhagic stroke (OR 0.18; 95% CI 0.03-1.05), cardiovascular death (OR 0.78; 95% CI 0.38-1.62), and all-cause mortality (OR 0.94; 95% CI 0.55-1.62) were not significantly different among groups. Major bleeding was significantly lower in patients treated with NOAC (2.8%) compared with warfarin (4.7%) (OR 0.49; 95% CI 0.28-0.88; P = .02). CONCLUSIONS: In patients with atrial fibrillation and bioprosthetic valves or valve repair, NOACs are associated with a reduced incidence of thromboembolic events and major bleeding as compared with warfarin. Thus, NOACs may be considered a preferred option for this patient population.

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

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.

The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients.

OBJECTIVE: Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin's impact on the decline in renal function from a large cohort with AF. METHODS: This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI). RESULTS: 3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p <  0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p <  0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: - 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461). CONCLUSIONS: During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.

Direct comparison of non-vitamin K antagonist oral anticoagulant versus warfarin for stroke prevention in non-valvular atrial fibrillation: a systematic review and meta-analysis of real-world evidences.

BACKGROUND: To overcome the several drawbacks of warfarin, non-vitamin K antagonist oral anticoagulants (NOACs) were developed. Even though randomized controlled trials (RCTs) provided high-quality evidence, the real-world evidence is still needed. This systematic review and meta-analysis proposed to measure the safety and efficacy profile between warfarin and NOACs in non-valvular atrial fibrillation (NVAF) patients in preventing stroke. RESULTS: We collected articles about the real-world studies comparing warfarin and NOACs for NVAF patients recorded in electronic scientific databases such as Embase, ProQuest, PubMed, and Cochrane. The pooled hazard ratio (HR) and 95% confidence interval (CI) were estimated using the generic inverse variance method. A total of 34 real-world studies, including 2287288 NVAF patients, were involved in this study. NOACs effectively reduced the stroke risk than warfarin (HR 0.77; 95% CI 0.69 to 0.87; p < 0.01). Moreover, NOACs effectively lowered all-cause mortality risk (HR 0.71; 95% CI 0.63 to 0.81; p < 0.01). From the safety aspect, compared to warfarin, NOACs significantly reduced major bleeding risk (HR 0.68; 95% CI 0.54 to 0.86; p < 0.01) and intracranial bleeding risk (HR 0.54; 95% CI 0.42 to 0.70; p < 0.01). However, NOACs administration failed to decrease gastrointestinal bleeding risk (HR 0.78; 95% CI 0.58 to 1.06; p = 0.12). CONCLUSIONS: In NVAF patients, NOACs were found to be more effective than warfarin at reducing stroke risk. NOACSs also lowered the risk of all-cause mortality, cerebral hemorrhage, and severe bleeding in NVAF patients compared to warfarin.

Efficacy and Safety of Direct Oral Anticoagulants in Venous Thromboembolism Compared to Traditional Anticoagulants in Morbidly Obese Patients: A Systematic Review and Meta-Analysis.

Background Randomized clinical trials comparing the efficacy and safety of direct oral anticoagulants (DOAC) with vitamin K antagonist (VKA) or low molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) generally exclude patients who are morbidly obese (body mass index ≥ 40 kg/m2 or weight ≥ 120 kg). Recently, smaller studies have compared DOACs with warfarin or low molecular weight heparin (LMWH) in morbidly obese patients with VTE. We aim to systematically review and do a meta-analysis of the studies that directly compared DOACs with VKAs or LMWH in morbidly obese patients. Methods Studies comparing DOAC with warfarin or LMWH in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, clinicaltrials.gov, and the Cochrane Library up to March 2020. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) guidelines. Study-specific odds ratios (OR) were calculated and combined using a random-effects model meta-analysis. Result Five studies were identified. Recurrent VTE occurred in 95 of 3207 (2.96%) patients in the DOAC group and 81 of 3181 (2.54%) patients in the VKA and LMWH group (OR: 1.17; 95% CI 0.87 to 1.59, p=.30). Major bleeding occurred in 63 of 3316 (1.89%) patients in the DOAC group, and 83 of 3259(2.54%) patients in the VKA or LMWH group (OR: 0.74; 95% CI: 0.53 to 1.03, p=.08). Sensitivity analysis comparing factor Xa inhibitors apixaban and rivaroxaban to warfarin also yielded consistent findings. Conclusion DOACs showed similar efficacy and safety in the prevention of recurrent VTE risk and major bleeding events in morbidly obese patients when compared to warfarin/LMWH. Our study underscores the need for further modifications of therapy to reduce the high VTE recurrence rate irrespective of whether the patient is on a DOAC or VKA. This might be possible through a very large multi-institutional randomized clinical trial.

Longitudinal Patterns in Antithrombotic Therapy in Patients with Atrial Fibrillation after Percutaneous Coronary Intervention in the Non-Vitamin K Oral Anticoagulant Era: A Nationwide Population-Based Study.

We investigated whether longitudinal patterns in antithrombotic therapy have changed after the introduction of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI). Using a claims database of the Korean AF population who underwent PCI between 2012 and 2016 (n = 18,691), we analyzed prescription records of oral anticoagulants (OACs) and antiplatelets at 3-month intervals over 2 years after PCI. The study population was stratified (pre-NOAC, transition, and NOAC era) using time-periods of NOAC introduction in Korea and an expansion of reimbursement for NOAC in AF as indicators. The overall rates of OAC were low at baseline (24.9%, 26.9%, and 35.2% in pre-NOAC, transition, and NOAC era, respectively), contrary to high rates of dual antiplatelet therapy (DAPT) (73.3%, 71.4%, and 63.6%). However, OAC prescription rates were increased at 1-year (18.5%, 22.5%, and 31.6%), and 2-year follow-up (17.8%, 24.2%, and 31.8%) from pre-NOAC to NOAC era. In NOAC era, 63.5% of baseline OAC prescriptions comprised NOAC, of which 96.4% included triple therapy with DAPT. Over 2 years, we observed increasing rates of double therapy with a single antiplatelet (18.3% and 20.0% at 1- and 2-year follow-up) and OAC monotherapy (2.7% and 8.9% at 1- and 2-year follow-up).