Occurrence of intraocular hemorrhages under monotherapy or combination therapy of antiplatelets and anticoagulants using the Japanese Adverse Drug Event Report database.

Purpose: An intraocular hemorrhage is an adverse event that can lead to visual acuity impairment. Antithrombotic therapy with antiplatelet agents and anticoagulants may increase intraocular hemorrhage. However, since their frequency is low, studies on the risk of intraocular hemorrhage with these drugs, especially under combination therapy, are limited. This study aimed to investigate the occurrence of intraocular hemorrhages under monotherapy and combination therapy with antiplatelets and anticoagulants by analyzing a large pharmacovigilance database. Methods: Intraocular hemorrhage signals with oral antiplatelets and anticoagulants were evaluated by calculating reporting odds ratios and information components using the Japan Adverse Drug Reactions Report database from April 2004 to March 2022. In addition, differences in signals between younger and elderly patients, affecting factors, and time-to-onset from initial antiplatelet and anticoagulant treatments were analyzed. Results: Aspirin, clopidogrel, warfarin, apixaban, and rivaroxaban, but not ticagrelor, ticlopidine, prasugrel, dabigatran, and edoxaban showed intraocular hemorrhage signals under monotherapy. In combination therapy, dual therapy (aspirin + P2Y12 inhibitors, warfarin, direct oral anticoagulants, and P2Y12 inhibitors + warfarin) and triple therapy (aspirin + P2Y12 inhibitors + warfarin) resulted in intraocular hemorrhage signals. Intraocular hemorrhage signals were observed in younger patients receiving monotherapy with aspirin and in elderly patients receiving monotherapy and combination therapy with warfarin. Affecting factors were diabetes mellitus in patients with prasugrel, use of medications for intravitreal injections, and posterior sub-Tenon injections with some antiplatelets and anticoagulants. The median period of intraocular hemorrhage occurrence after starting monotherapy with aspirin, clopidogrel, warfarin, or rivaroxaban was within 90 days. Conclusion: In addition to monotherapy with several antiplatelets and anticoagulants, combination therapy using aspirin, P2Y12 inhibitors, and warfarin has the potential risk of intraocular hemorrhage. Particular attention should be paid to the occurrence of intraocular hemorrhages in younger patients taking aspirin, in elderly patients taking warfarin, and within the first 90 days of antiplatelet and anticoagulant use.

Oral anticoagulant switching in patients with atrial fibrillation: a scoping review.

INTRODUCTION: Oral anticoagulants (OACs) prevent stroke in patients with atrial fibrillation (AF). Several factors may cause OAC switching. OBJECTIVES: To examine the phenomenon of OAC switching in patients with AF, including all available evidence; frequency and patterns of switch, clinical outcomes, adherence, patient-reported outcomes, reasons for switch, factors associated with switch and evidence gaps. DESIGN: Scoping review. DATA SOURCES: MEDLINE, Embase and Web of Science, up to January 2022. RESULTS: Of the 116 included studies, 2/3 examined vitamin K antagonist (VKA) to direct-acting OAC (DOAC) switching. Overall, OAC switching was common and the definition of an OAC switch varied across. Switching from VKA to dabigatran was the most prevalent switch type, but VKA to apixaban has increased in recent years. Patients on DOAC switched more to warfarin than to other DOACs. OAC doses involved in the switches were hardly reported and patients were often censored after the first switch. Switching back to a previously taken OAC (frequently warfarin) occurred in 5%-21% of switchers.The risk of ischaemic stroke and gastrointestinal bleeding in VKA to DOAC switchers compared with non-switchers was conflicting, while there was no difference in the risk of other types of bleeding. The risk of ischaemic stroke in switchers from DOAC versus non-switchers was conflicting. Studies evaluating adherence found no significant changes in adherence after switching from VKA to DOAC, however, an increase in satisfaction with therapy were reported. Reasons for OAC switch, and factors associated with OAC switch were mostly risk factors for stroke and bleeding. Clinical outcomes, adherence and patient-reported outcomes were sparse for switches from DOACs. CONCLUSIONS: OAC switching is common in patients with AF and patients often switch back to an OAC they have previously been on. There are aspects of OAC switching that have received little study, especially in switches from DOACs.

The gray areas of oral anticoagulation for prevention of thromboembolic events in atrial fibrillation patients.

Thromboembolic events (TEE) associated with atrial fibrillation (AF) are highly recurrent and usually severe, causing permanent disability or, even, death. Previous data consistently showed significantly lower TEE in anticoagulated patients. While warfarin, a vitamin K antagonist, is still used worldwide, direct-acting oral anticoagulants (DOACs) have shown noninferiority to warfarin in the prevention of TEE, and represent, to date, the preferred treatment. DOACs present favorable pharmacokinetic, safety and efficacy profiles, especially among vulnerable patients including the elderly, those with renal dysfunction or previous TEE. Yet, regarding specific settings of AF patients it is unclear whether oral anticoagulation therapy is beneficial, or otherwise it is the maintenance of sinus rhythm, mostly achieved through a catheter ablation-based rhythm control strategy, that prevents the causal complications linked to AF. While it is known that low-risk patients [CHA2DS2-VASc 0 (males), or score of 1 (females)] present low ischemic stroke or mortality rates (<1%/year), it remains unclear whether they need any prophylaxis. Furthermore, the appropriate anticoagulation regimen for those individuals requiring cardioversion, either pharmacologic or electric, as well as peri-procedural anticoagulation in patients undergoing trans-catheter ablation that nowadays encompasses different energies, are still a matter of debate. In addition, AF concomitant with other clinical conditions is discussed and, lastly, the choice of prescribing anticoagulation to asymptomatic patients diagnosed with subclinical AF at either wearable or implanted devices. The aim of this review will be to provide an update on current strategies in the above-mentioned settings, and to suggest possible therapeutic options, finally focusing on AF-related cognitive decline.

Factors Affecting Recanalization in Femoropopliteal Deep Vein Thrombosis.

Effects of warfarin and new-generation direct oral anticoagulants (DOACs) on thrombus resolution after the treatment of deep vein thrombosis (DVT) are still unknown. The study aimed to investigate the effects of warfarin and DOACs on thrombus resolution after DVT treatment. Methods: The study included 666 patients who were diagnosed with femoropopliteal DVT between January 2016 and January 2022 and had complete medical records without missing data. Patients with and without recanalization were added to groups 1 (n = 396) and 2 (n = 270), respectively. Ultrasonography/venous Doppler examinations of the patients during follow-up were performed by 3 radiologists. Recanalization was defined as the presence of complete flow in the femoral and popliteal veins and the absence of residual venous thrombus. Results: Among the included patients, recanalization was observed in 59.5% patients. The mean follow-up period was 23.6 ± 17.8 (range 1-72; median 17) months. There was no difference between the 2 groups in terms of the types of drugs used in the treatment (P = .208). Cox regression models were used to investigate the factors affecting recanalization. Analysis of the variables having significant differences between both groups revealed the low rate of recanalization in patients with coronary artery disease (odds ratio [OR], 2.3%; 95% confidence intervals [CI]: 1.6-3.4; P < .001) and diabetes mellitus (OR, 1.5; 95% CI: 1.1-1.9; P = .009). Conclusion: Thrombus resolution after femoropopliteal DVT is not affected by the drugs used in the treatment.

Outcomes of SUBGALEAL Drain Placement after two Burr-Holes Craniectomy for Chronic Subdural Hematoma.

OBJECTIVE: To evaluate the efficacy and complications of subgaleal drain placement after two burr-holes evacuation of chronic subdural hematoma (CSDH). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Neurosurgical unit of the Lady Reading Hospital, Peshawar, from April to November 2021. METHODOLOGY: Sixty-four consecutive patients diagnosed with surgically significant unilateral chronic subdural hematoma were prospectively included after obtaining informed consent. All the patients underwent two burr-holes craniectomies and evacuation, followed by subgaleal drain placement. Patient demographics, pre- and postoperative clinical information including hematoma resolution and complications were collected. RESULTS: This study included 44 (69%) males and 20 (31%) females with a mean age of 70.1 ± 8 years. The most common presenting symptoms were headaches (70%) and confusion (68%). Eighteen patients (28%) were taking warfarin or other anticoagulants, whereas, 23 patients (36%) were taking antiplatelet medications at the time of presentation. Thirty-six (56.3%) patients had a history of head trauma. Warfarin use was statistically significant in the patients with no history of head injury. Fifty-five patients (85%) showed no significant recurrence on the 2 week postoperative computed tomography (CT) scan. None of the patients had intraparenchymal hematoma or contusion of iatrogenic origin on postoperative CT scans. CONCLUSION: Subgaleal drain placement after two burr-holes craniectomy led to high-resolution rates. However, no parenchymal injuries were attributed to the procedure. KEY WORDS: Chronic subdural hematoma, Subdural drain, Subperiosteal drain, Burr-hole craniostomy.

Penile calciphylaxis in a patient with concurrent haemodialysis and Coumadin treatment.

A man in his 30s, with a medical history of end-stage renal disease on haemodialysis three times a week after kidney transplant rejection, anaemia of inflammatory disease, hypertension, atrial fibrillation, hyperlipidaemia, subtotal parathyroidectomy and aortic valve replacement on Coumadin treatment, presented to our institution with glans penis pain. Examination of the penis revealed a painful black eschar with ulceration on the glans penis with surrounding erythema. CT scan of the abdomen and pelvis and penile Doppler ultrasound revealed calcifications of the abdominal, pelvic and penile blood vessels. He was diagnosed with penile calciphylaxis, a very rare manifestation of calciphylaxis characterised by penile blood vessel calcification leading to occlusion, ischaemia and necrosis. Treatment with low calcium dialysate and sodium thiosulfate was initiated with haemodialysis. Five days after the treatment started, the patient's symptoms improved.

Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients.

PURPOSE: Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation with DOACs compared to warfarin. METHODS: We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling. RESULTS: The median follow-up was longer for RTRs on warfarin (1098 days [IQR 521, 1517]) than DOACs (449 days [IQR 338, 942]). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been. CONCLUSIONS: DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.

Profile and outcome of patients with Warfarin Toxicity admitted in a tertiary care hospital in Bhutan: a cross-sectional study investigators and institutions.

OBJECTIVE: To study the profile, clinical presentation and outcome of hospital stay among patients admitted with warfarin toxicity at the Jigme Dorji Wangchuck National Referral Hospital, Bhutan. This was a cross-sectional study with a review of hospital records of patients admitted between 01 and 2018 and 30 June 2020. RESULTS: There were 22 admissions due to warfarin toxicity. The mean age of patients was 55.9 (± SD 20.2) years, the median duration of warfarin therapy was 30 months (IQR 4.8, 69 months). The indications for warfarin were atrial fibrillation (9, 40.9%), mechanical heart valves (6, 27.3%), deep vein thrombosis (6, 27.3%) and pulmonary thromboembolism (1, 4.5%). The mean of dosage of warfarin was 4.3 (± 2.6) mg and the cumulative dosage in the week prior to admission was 30.9 (± 18.6) mg. The mean of INR at presentation was 7.7 (± 4.3) with the maximum noted at 20. The patients presented with gastrointestinal bleeding, muscle haematomas, epistaxis and oral cavity bleeding. There was no mortality related to warfarin toxicity. The reasons for warfarin toxicity included patient dosing error and drug interactions. Warfarin therapy requires appropriate patient education, adequate facilities for follow-up and avoidance of warfarin wherever possible in clinical settings.

Standard-Intensity Versus Low-Intensity Anticoagulation with Warfarin in Asian Patients with Atrial Fibrillation: A Multi-Center, Randomized Controlled Trial.

Anticoagulation with warfarin in Asian patients with atrial fibrillation (AF) often has been decreased as an international normalized ratio (INR) of prothrombin time 1.6-2.6 due to fear of bleeding, although universal criteria recommend an INR of 2.0-3.0. In this randomized, open-label trial, low-intensity anticoagulation (INR 1.6-2.6) was compared with standard-intensity anticoagulation (INR 2.0-3.0) with warfarin. A total 616 patients with AF and at least 1 risk factor for stroke were randomized to low-intensity anticoagulation (n = 308) and standard-intensity anticoagulation (n = 308) groups. The intention-to-treat analysis was performed to determine differences. The baseline characteristics of the two groups were comparable. New-onset stroke occurred in 2 patients (0.44% per year) in the low-intensity group and 5 patients (1.05% per year) in the standard-intensity group (HR 0.42, 95% CI 0.08-2.15). Major bleeding occurred in 4 patients (0.89% per year) in the low-intensity group and 5 patients (1.06% per year) in the standard-intensity group (HR 0.84, 95% CI 0.22-3.11). The rate of the net clinical outcome (composite of stroke, systemic embolism, major bleeding, and death) was 1.33% per year in the low-intensity group compared with 2.12% per year in the standard-intensity group (HR 0.63, 95% CI 0.23-1.72). In Asian patients with AF, clinical outcomes were not different between low-intensity and standard-intensity anticoagulation with warfarin.

Detailed Experimental and In Silico Investigation of Indomethacin Binding with Human Serum Albumin Considering Primary and Secondary Binding Sites.

The interaction of indomethacin with human serum albumin (HSA) has been studied here considering the primary and secondary binding sites. The Stern-Volmer plots were linear in the lower concentration range of indomethacin while a downward curvature was observed in the higher concentration range, suggesting the presence of more than one binding site for indomethacin inside HSA due to which the microenvironment of the fluorophore changed slightly and some of its fraction was not accessible to the quencher. The Stern-Volmer quenching constants (KSV) for the primary and secondary sites were calculated from the two linear portions of the Stern-Volmer plots. There was around a two-fold decrease in the quenching constants for the low-affinity site as compared to the primary binding site. The interaction takes place via a static quenching mechanism and the KSV decreases at both primary and secondary sites upon increasing the temperature. The binding constants were also evaluated, which show strong binding at the primary site and fair binding at the secondary site. The binding was thermodynamically favorable with the liberation of heat and the ordering of the system. In principle, hydrogen bonding and Van der Waals forces were involved in the binding at the primary site while the low-affinity site interacted through hydrophobic forces only. The competitive binding was also evaluated using warfarin, ibuprofen, hemin, and a warfarin + hemin combination as site markers. The binding profile remained unchanged in the presence of ibuprofen, whereas it decreased in the presence of both warfarin and hemin with a straight line in the Stern-Volmer plots. The reduction in the binding was at a maximum when both warfarin and hemin were present simultaneously with the downward curvature in the Stern-Volmer plots at higher concentrations of indomethacin. The secondary structure of HSA also changes slightly in the presence of higher concentrations of indomethacin. Molecular dynamics simulations were performed at the primary and secondary binding sites of HSA which are drug site 1 (located in the subdomain IIA of the protein) and the hemin binding site (located in subdomain IB), respectively. From the results obtained from molecular docking and MD simulation, the indomethacin molecule showed more binding affinity towards drug site 1 followed by the other two sites.

Clinical Characteristics, Patterns of Use, and incidence of Adverse Events in Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants in Colombia.

Purpose: The aim was to analyze the characteristics, treatment patterns, and clinical outcomes of Colombian patients with non-valvular atrial fibrillation (NVAF) under treatment with oral anticoagulants (OAs). Patients and Methods: Retrospective cohort in patients with NVAF identified from a drug dispensing database, aged ≥18 years, with first prescription of an OA (index) between January/2013 and June/2018, and a follow-up until June/2019. Data from the clinical history, pharmacological variables, and outcomes were searched. International Classification of Diseases-10 codes were used to identify the patient sample and outcomes. Patients were followed until a general composite outcome of effectiveness (thrombotic events), bleeding/safety or persistence (switch/discontinuation of anticoagulant) events. Descriptive and multivariate analyzes (Cox regressions comparing warfarin and direct oral anticoagulants-DOACs) were carried out. Results: A total of 2076 patients with NVAF were included. The 57.0% of patients were women and the mean age was 73.3±10.4 years. Patients were followed for a mean of 2.3±1.6 years. 8.7% received warfarin before the index date. The most frequent OA was rivaroxaban (n=950; 45.8%), followed by warfarin (n=459; 22.1%) and apixaban (n=405; 19.5%). Hypertension was present in 87.5% and diabetes mellitus in 22.6%. The mean CHA2DS2-VASc Score was 3.6±1.5. The 71.0% (n=326/459) of the warfarin patients presented the general composite outcome, and 24.6% of those with DOACs (n=397/1617). The main effectiveness and safety outcomes were stroke (3.1%) and gastrointestinal bleeding (2.0%) respectively. There were no significant differences between patients with warfarin and DOACs regarding thrombotic events (HR: 1.28; 95% CI: 0.68-2.42), but warfarin was associated with higher bleeding/safety events (HR: 4.29; 95% CI: 2.82-6.52) and persistence events (HR: 4.51; 95% CI: 3.81 -5.33). Conclusion: The patients with NVAF in this study were mainly older adults with multiple comorbidities. Compared to warfarin, DOACs were found to be equally effective, but safer and had a lower probability of discontinuation or switch.

Left Atrial Appendage Closure: What the Evidence Does and Does Not Reveal-A View from the Outside.

This review summarizes the evidence for left atrial appendage closure (LAAC) as an alternative to oral anticoagulation (OAC) for stroke prevention in atrial fibrillation. LAAC reduces hemorrhagic stroke and mortality versus warfarin, but is inferior for ischemic stroke reduction based on randomized data. Whilst a feasible treatment in OAC-ineligible patients, questions remain over procedural safety, and the improvement in complications observed in nonrandomized registries is uncorroborated by contemporary randomized trials. Management of device-related thrombus and peridevice leak remain unclear, and robust randomized data versus direct OACs are required before recommendations can be made for widespread adoption in OAC-eligible populations.

Choosing safe and effective anticoagulation to treat idiopathic ovarian vein thrombosis: using first principles of deep vein thrombosis management to treat a rare diagnosis: a case report and review of the literature.

BACKGROUND: Ovarian vein thrombosis (OVT) often presents in the post-partum period and is associated with significant complications including inferior vena cava extension, pulmonary embolism, sepsis, and renal obstruction. Idiopathic OVT is rare, and no consensus has been agreed upon regarding its diagnosis and management. This case presents a patient who was diagnosed with idiopathic OVT and was treated with apixaban. A literature review was performed collating reported cases of idiopathic OVT to form a recommendation regarding optimal management and follow up. CASE PRESENTATION: A 42-year-old Chinese woman presenting with right lower quadrant pain underwent a CT abdomen after urinary tract obstruction was excluded on ultrasound. She was subsequently diagnosed with an idiopathic 35 mm ovarian vein thrombus (OVT) given no history of primary coagulopathy nor secondary aetiology. A literature review was performed collating 18 case reports with method of diagnosis and management summarized. Treatment alternatives included low molecular weight heparin, warfarin, rivaroxaban and apixaban. Most were diagnosed after work up for suspected renal calculus or appendicitis. Follow up imaging was performed from between 6 weeks to 6 months after initiation of anticoagulation. CONCLUSIONS: Direct oral anticoagulants were an effective treatment for OVT, however warfarin should be commenced in those suspected of antiphospholipid syndrome awaiting confirmation or exclusion of the diagnosis.

Bleeding related to oral anticoagulants: Trends in US emergency department visits, 2016-2020.

BACKGROUND: Clinical trials suggest lower rates of major bleeding with direct-acting oral anticoagulants (DOACs) than with warfarin, but anticoagulant-related bleeding remains one of the most common outpatient adverse drug events. METHODS: We estimated the number of emergency department (ED) visits and subsequent hospitalizations for oral anticoagulant-related bleeding in 2016-2020 based on active surveillance in a nationally representative, size-stratified probability sample of 60 U.S. hospitals. We estimated rates of ED visits using a nationally-projected retail prescription dispensing database. RESULTS: Based on 19,557 cases, oral anticoagulant-related bleeding resulted in an estimated 1,270,259 (95 % Confidence Interval [CI], 644,686-1,895,832) ED visits for the five years 2016-2020, of which 47.8 % (95 % CI, 40.6 %-55.0 %) resulted in hospitalization. Oral anticoagulant-related bleeding resulted in an estimated 230,163 (95% CI, 109,598-350,728) ED visits in 2016 and 301,433 (95% CI, 138,363-464,503) in 2020. During 2016-2020, ED visits for DOAC-related bleeding increased by an average of 27.9 % (95 % CI, 24.0 %-32.0 %; p < .001) per year, while ED visits for warfarin-related bleeding decreased by an average of 8.8 % (95 % CI, -10.7 % to -7.0 %; p = .001) per year. The estimated rate of bleeding visits per 100 patients dispensed oral anticoagulants at least once in 2016-2020 was highest for patients aged ≥ 80 years (13.1; 95 % CI, 6.2-20.0) and lowest for those aged <45 years (4.0; 95 % CI, 2.6-5.5); it was 5.9 visits per 100 patients dispensed DOACs [95 % CI, 2.5-9.2] and 13.0 visits per 100 patients dispensed warfarin [95 % CI, 7.4-18.7]. CONCLUSIONS: Although the rates of ED visits for anticoagulant-related bleeding may be lower for DOACs than for warfarin, persistently large numbers of patients requiring ED visits for anticoagulant-related bleeding despite increased use of DOACs and declining use of warfarin suggest that efforts to improve appropriate prescribing and monitoring of anticoagulants remain important.

Aortic Stenosis and Outcomes in Patients With Atrial Fibrillation: A Nationwide Cohort Study.

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Oral anticoagulants and concurrent rifampin administration in tuberculosis patients with non-valvular atrial fibrillation.

BACKGROUND: Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited. METHODS: Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes. RESULTS: Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499). CONCLUSIONS: In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

PURPOSE OF REVIEW: Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. RECENT FINDINGS: Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90 days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Quality of anticoagulant control and patient experience associated with long-term warfarin in Canadian patients with non-valvular atrial fibrillation: A multicentre, prospective study.

BACKGROUND: Despite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients. OBJECTIVES: In a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy. METHODS: Five hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori). RESULTS: Four hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient's province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment. CONCLUSIONS: We showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients' health related quality of life or daily work and activities was low.