Effect Of Warfarin Research Articles

Outcomes Associated with Novel Oral Anticoagulants and Warfarin in Patients with Cardiac Thrombus Following STEMI.

The treatment of cardiac thrombus after ST-segment elevation myocardial infarction (STEMI) is anticoagulation. There is conflicting data on effectiveness and safety of novel oral anticoagulants (NOACs) vs. warfarin. Using the national Medicare data, we identified patients with an admission diagnosis of STEMI and cardiac thrombus within six months after STEMI. Patients were divided into two groups based on initial type of anticoagulation medication (NOACs vs. warfarin). The two main outcomes were ischemic stroke/transient ischemic attack (TIA) and bleeding. Follow-up was performed through the end of 2023. Kaplan-Meier (KM) Curves and Cox proportional hazard models were utilized. Of 881 patients prescribed anticoagulation after STEMI with subsequent cardiac thrombus, 496 patients were prescribed NOACs (56.3%) and 385 patients (43.7%) warfarin. For ischemic stroke, the median follow-up time was 177 days (95% CI: 148-193) for warfarin and 266 days (95% CI: 204-326) for NOACs. There was significantly lower risk of ischemic stroke or TIA in cardiac thrombus patients treated with NOACs compared to warfarin [HR 0.73 (0.57-0.93)]. For bleeding, the median follow-up time was 192 days (95% CI: 175-232) for warfarin and 277 days (95% CI: 212-332) for NOACs. There was also a lower risk of bleeding in patients treated with NOACs compared to warfarin [HR 0.78 (CI 0.66-0.92)]. In conclusion, STEMI patients with cardiac thrombus had lower risk of ischemic stroke and bleeding when treated with NOACs compared to warfarin. Prospective randomized studies are needed to confirm these findings and further examine the comparative effectiveness of different anticoagulant strategies.

Comparison of interrupted and uninterrupted anticoagulation strategies for cardiac implantable electronic device insertion: a systematic review and meta-analysis

Abstract Introduction Up to 35% of patients who are candidates for a cardiac implantable electronic device (CIED) receive chronic anticoagulation. However, guidelines on anticoagulant management in the perioperative period of CIED insertion differ worldwide. It is uncertain whether interrupting or continuing anticoagulation in these settings provides optimal outcomes. Purpose To assess the effects of interrupting versus continuing chronic anticoagulation with either warfarin or a direct oral anticoagulant (DOAC) in the perioperative setting of CIED insertion. Methods CENTRAL, MEDLINE, Embase, Web of Science, and two trial registries were searched from inception to 26 November 2021. Randomised controlled trials (RCTs) assessing interrupting chronic warfarin or DOAC therapy, with or without heparin bridging, versus continuing anticoagulation in adults undergoing CIED insertion were included. Comparisons were divided into two categories: interrupted versus uninterrupted warfarin and interrupted versus uninterrupted DOAC. Outcomes were expressed as risk ratios (RR) with 95% confidence intervals (95%CI). Inverse variance random-effects models were used for the meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool, and certainty of evidence (CoE) per outcome was assessed with GRADE methods. Results Ten RCTs (n=2221) were included: five RCTs (n=1267) used warfarin; four RCTs (n=954) used DOACs. One additional RCT using warfarin was ongoing without any outcome data available. Bleeding events included device-pocket haematoma, haemothorax, cardiac tamponade, and non-tamponade pericardial effusion. Interrupted versus uninterrupted warfarin: The evidence is very uncertain on the effect of interrupted warfarin on device-pocket haematoma (RR 1.89, 95%CI 0.85 to 4.20, 5 RCTs, very low CoE) and bleeding events (RR 1.94, 95%CI 0.86 to 4.41, 5 RCTs, very low CoE). Interrupted warfarin may result in little to no difference in thromboembolic events (RR 0.85, 95%CI 0.18 to 4.11, 5 RCTs, low CoE) and ischaemic stroke (RR 1.01, 95%CI 0.11 to 9.61, 2 RCTs, low CoE). Interrupted warfarin may reduce all-cause mortality (RR 0.35, 95%CI 0.04 to 2.93, 3 RCTs, low CoE). Interrupted versus uninterrupted DOAC: The evidence is very uncertain on the effect of interrupted DOAC on device-pocket haematoma (RR 1.15, 95%CI 0.58 to 2.28, 4 RCTs, very low CoE) and bleeding events (RR 1.14, 95%CI 0.58 to 2.21, 4 RCTs, very low CoE). Interrupted DOAC may result in little to no difference in thromboembolic events (RR 0.98, 95%CI 0.06 to 15.63, 3 RCT, low CoE) and ischaemic stroke (RR 0.98, 95%CI 0.06 to 15.63, 2 RCTs, low CoE). Interrupted DOAC may reduce all-cause mortality slightly (RR 0.49, 95% CI 0.04 to 5.39, 2 RCTs, low CoE). Conclusion Interrupting anticoagulation with either warfarin or DOACs in patients undergoing CIED insertion produced similar outcomes as uninterrupted anticoagulation.Figure 1.Figure 2.

Antibiotic prescribing patterns and risk of antibiotic-resistant infections and Clostridium difficile in Warfarin and Direct Oral Anticoagulant users: matched population-based cohort study

BackgroundWarfarin and Direct Oral Anticoagulant (DOAC) users may have more frequent antibiotic prescriptions than non-users. The aim of this study was to estimate rates of common and resistant infections, and antibiotic prescribing amongst warfarin and DOAC users versus non-users.MethodsThis matched retrospective cohort study used data from patients registered with General practices in England contributing to the Clinical Practice Research Datalink GOLD. We included 61,750 adults who initiated warfarin or a DOAC between 1st January 2011 and 31st December 2019, matched 1:1 to non-users. We estimated Incident Rate Ratios (IRR) and 95% Confidence Intervals for three common infections and all-cause antibiotic prescribing. We estimated hazard ratios (HRs) and 95% CIs for the risk of methicillin resistance Staphylococcus aureus (MRSA), other antibiotic-resistant organisms, or Clostridium difficile. We assessed the extent to which any of the effect of warfarin and DOAC use on antibiotic resistant infections or Clostridium difficile was mediated by antibiotic prescribing patterns.Results37,143 warfarin users and 24,607 DOAC users were matched 1:1 to non-users. Warfarin and DOAC users had greater relative consultation rates for respiratory, urinary, and skin infections. All-cause antibiotic prescribing was greater in warfarin and DOAC users (warfarin; adjusted IRR 1.47, 95% CI 1.45–1.50, DOAC; adjusted IRR 1.66, 95% CI 1.63–1.69). Largest effect sizes were observed for flucloxacillin (adjusted IRR 2.11, 95% CI 2.01–2.20), and erythromycin (adjusted IRR 2.32, 95% CI 2.00–2.70). Warfarin users had significantly higher risk of MRSA (adjusted HR 1.68, 95% CI 1.38–2.05) and hospital admission with antibiotic resistant infections (adjusted HR 1.91, 95% CI 1.11–3.30). DOAC users had significantly higher risk of MRSA (adjusted HR 1.57, 95% CI 1.20–2.06), hospital admission with antibiotic resistant infections (adjusted HR 2.13, 95% CI 1.61–2.82), and Clostridium difficile (adjusted HR 1.45, 95% CI 1.10–1.92). We found little evidence to suggest that the increased risks of studied outcomes were mediated by rates of antibiotic prescription.ConclusionWarfarin and DOAC use was associated with greater rates of infection consultations, all-cause antibiotic prescribing, antibiotic resistant infections, and Clostridium difficile, but there was little evidence that antibiotic prescribing rates mediated risk of resistant infections or Clostridium difficile.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study

ObjectiveResidents of nursing homes are usually excluded from clinical trials, including trials to assess treatments for common conditions such as nonvalvular atrial fibrillation (NVAF). We aimed to quantify the real-world comparative safety and effectiveness of direct-acting oral anticoagulants (DOACs) vs warfarin among nursing home residents with NVAF. DesignRetrospective cohort study using 100% national Minimum Data Set and linked Medicare claims from January 2011 through December 2018. Setting and ParticipantsLong-term care nursing home residents aged ≥66 years enrolled in fee-for-service Medicare. We included individuals diagnosed with NVAF newly initiating oral anticoagulants. MethodsWe identified exposure to DOACs (apixaban, dabigatran, rivaroxaban, and edoxaban) vs warfarin. Outcomes were hospitalization for ischemic stroke/systemic embolism, major bleeding, pneumonia (negative control outcome), and all-cause death. We used inverse probability of treatment weighting competing risk regression models for clinical outcomes and Cox proportional hazards regression for all-cause death. ResultsOf 38,983 individuals newly initiating anticoagulants, 19,366 (49.7%) initiated DOACs and 19,617 (50.3%) initiated warfarin. In the inverse probability of treatment weighting analysis, compared with warfarin, there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84–1.05] or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96–1.10). DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91–0.98). Conclusions and ImplicationsAmong nursing home residents with NVAF, DOACs and warfarin were associated with a similar risk of ischemic stroke/systemic embolism and major bleeding. However, the use of DOACs was associated with a slightly reduced risk of all-cause mortality.

Direct Oral Anticoagulants for RheumaticHeart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95%CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Comparative Efficacy and Safety of Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients with Chronic Liver Disease: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia. Direct oral anticoagulants (DOACs), with superior efficacy and safety, have emerged as a promising alternative to warfarin. This systematic review and meta-analysis aimed to compare the safety and efficacy of DOACs and warfarin in patients with AF and chronic liver disease (CLD). A systematic search was undertaken in PubMed, the Cochrane Library, and Google Scholar to identify studies comparing the effectiveness of DOACs and warfarin in patients diagnosed with AF and CLD. Subsequent analyses were carried out using the random-effects model. This meta-analysis included eight studies involving 20,684 participants; baseline characteristics indicated a prevalent male presence (56.7%), with an average age of 61.63 ± 9 years. Primary outcomes demonstrated that DOACs were associated with significantly reduced all-cause mortality (relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.95; I 2 = 84%; P = .02) and ischemic stroke risk (RR, 0.62; 95% CI, 0.45-0.86; I 2 = 61%; P = .004). Secondary outcomes revealed a significantly reduced risk of major bleeding with DOACs compared to warfarin, while gastrointestinal bleeding showed a non-significant decrease. Intracranial hemorrhage risk was significantly lower with DOACs compared to warfarin. DOACs demonstrate superior safety and efficacy compared to warfarin, evidenced by reduced rates of all-cause death, ischemic stroke, severe bleeding, and cerebral hemorrhage. Further randomized controlled trials are essential to enhance the evidence base for DOACs across diverse patient populations.

Feto-Maternal Complications of Anticoagulant Use Before and After Childbirth

Anticoagulants prevent blood clotting, but their use in pregnancy poses challenges due to bleeding risks, particularly during delivery and postpartum. Objectives: To evaluate the maternal and fetal complications associated with anticoagulant use before and after childbirth, considering the safety and effectiveness of low molecular weight heparin and Warfarin. Methods: A cohort study was conducted at the Tertiary Care Hospital of Sindh, from August 2022 to July 2023. 266 pregnant women were chosen via consecutive sampling. Pregnant women with a gestational age of > 12 weeks, aged 18-35 years probably taking anti-coagulation therapy during pregnancy and puerperium were included in the study. While women suffering from any major systemic illness and women taking any other potential teratogenic drugs were excluded. Results: Maternal complications occurred in 53% of participants, with postpartum hemorrhage being the most frequent (19.9%), significantly higher in the low molecular weight heparin group (p<0.05). Pre-eclampsia affected 10.5% of participants, predominantly in low molecular weight heparin users (p=0.028). Fetal complications were reported in 59.3% of cases, with intrauterine growth restriction (13.5%) and premature birth (18.0%) being the most common. Stillbirths were more frequent among Warfarin users. Neonatal intensive care admission was required for 11.3% of infants, with low molecular weight heparin exposure showing the highest incidence. Conclusions: It was concluded that low molecular weight heparin was with poor maternal outcomes such as postpartum hemorrhage, wound hematoma, deep vein thrombosis, and pre-eclampsia, while fetal complications included intrauterine growth restriction, stillbirth, premature birth and low birth weight.

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non‐valvular atrial fibrillation in Japan

AbstractAimsThere are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non‐valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan.MethodsThis retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest‐neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE).ResultsAfter PS matching, 2955 DOAC‐ and 1603 warfarin‐treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β‐blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50–1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78–1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47–0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22–3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10–3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05–4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22–2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24–2.83).ConclusionsDOAC‐treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin‐treated patients. Prior stroke was shown to augment stroke risk by approximately three‐fold. This large real‐world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

Pharmacokinetic and Pharmacodynamic Interactions between Food or Herbal Products and Oral Anticoagulants: Evidence Review, Practical Recommendations, and Knowledge Gaps.

Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants. Since the RCT evidence was slim, we also reviewed prospective longitudinal studies, case series, and case reports to identify possible associations between foods and anticoagulation therapy. We referred to basic or translational studies that shared putative explanations for such interactions, but we failed to identify high-quality evidence in most cases. The limited evidence, small sample size of the studies, conflicting results, and possible heterogeneity in the contents of herbal products prevent a conclusive assessment of these interactions. Existing evidence suggests that (1) cranberry juice consumption (up to 240 mL/d and probably even more) with warfarin is safe; (2) use of green leafy vegetables with a high daily content (more than 250 µg) of vitamin K should be cautioned for patients receiving warfarin, because it may decrease warfarin efficacy. It is also advisable for patients to maintain highly constant intake of green leafy vegetables to ensure stable warfarin effectiveness; (3) ginger, even in small quantities (excluding commercial ginger-flavored beverages, which contain only negligible amounts of ginger), and mango (more than one fruit) can both potentiate warfarin effects; (4) patients taking OACs should avoid St. John's wort due to diminished anticoagulant effect; and (5) consumption of less than 240 mL of grapefruit juice daily is unlikely to interact with OACs. Future longitudinal observational cohort studies and RCTs with larger sample sizes are needed to study specific interactions between food or herbal products and OACs.

Safety and Effectiveness of Direct Oral Anticoagulants Versus Warfarin in Patients with Venous Thromboembolism using Real-World Data: A Systematic Review and Meta-Analysis.

Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs' effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE. A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis. A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69-0.85), major bleeding (HR 0.77, 95% CI 0.72-0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77-0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68-0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83-1.10). This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin.

Coronary thrombosis and myocardial ischemia in Kawasaki disease: a case report

BackgroundCoronary artery thrombosis and myocardial ischemia caused by giant coronary aneurysms are the main causes of death in children with Kawasaki disease. The use of thrombolytic therapy in children with Kawasaki disease who have coronary thrombosis is a controversial topic, especially with respect to the timing of treatment.Case presentationIn this article, we report a case of a child aged two years and nine months with Kawasaki disease whose coronary arteries had no involvement in the acute phase. However, by only one week after discharge, the patient returned because we found giant coronary aneurysms complicated by thrombosis via echocardiography. Despite aggressive thrombolytic therapy, the child developed myocardial ischemia during thrombolytic therapy. Fortunately, because of timely treatment, the child’s thrombus has dissolved, and the myocardial ischemia has resolved.ConclusionsThis case suggests that for patients at high risk of coronary artery aneurysms, echocardiography may need to be reviewed earlier. Low-molecular-weight heparin should be added to antagonize the early procoagulant effects of warfarin when warfarin therapy is initiated. In the case of first-detected coronary thrombosis, aggressive thrombolytic therapy may be justified, particularly during the acute and subacute phases of the disease course.

Comparative effectiveness and safety of direct oral anticoagulants and warfarin in atrial fibrillation patients with dementia.

Developing an effective stroke prevention strategy is crucial for elderly atrial fibrillation (AF) patients with dementia. This is due to the limited and inconsistent evidence available on this topic. In this nationwide, population-based cohort study, we aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in AF patients with dementia. We identified AF patients with dementia, aged 50 years or older, from Taiwan's National Health Insurance Research Database between 2010 and 2019. The primary outcome was a composite of hospitalizations due to ischemic stroke, acute myocardial infarction, intracranial hemorrhage, or major bleeding, as well as all-cause mortality. We used 1:1 propensity score matching and Cox proportional hazard models to adjust for confounding factors when comparing outcomes between warfarin and DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban) users or warfarin and each individual DOAC. There were 2952 patients in the DOAC-warfarin matched cohort. The apixaban-, dabigatran-, edoxaban-, and rivaroxaban-warfarin matched cohorts had 2346, 2554, 1684, and 2938 patients, respectively. The DOAC group, when compared to warfarin, was associated with a lower risk of both the composite outcome (hazard ratio (HR), 0.81; 95% confidence interval (CI) 0.69-0.95) and ischemic stroke (HR 0.65; 95% CI 0.48-0.87). Apixaban (HR 0.79; 95% CI 0.66-0.94), dabigatran (HR 0.64; 95% CI 0.53-0.77), and rivaroxaban (HR 0.82; 95% CI 0.70-0.97) were also associated with a lower risk of the composite outcome. Compared to warfarin, DOACs, whether as a group or apixaban, dabigatran, or rivaroxaban individually, were associated with a reduced risk of the composite outcome in elderly patients with concurrent AF and dementia.

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study

BackgroundThis retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China.MethodsA retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected.ResultsPatients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0–1, 2–3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0–1 (20.0%) than those with score 2–3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0–1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2–3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0–1 and 2–3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy.ConclusionCompared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0–1.

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. Population-based cohort study. Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). Nonrandomized treatment selection. Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. National Institutes of Health.

Observing INR Results in Patients Who Switched from Brand-Name to Generic Warfarin during the COVID-19 Pandemic at KAMC, Riyadh, Saudi Arabia

Abstract Background: Since the global spread of coronavirus disease 2019 (COVID-19), multiple challenges have faced the medical field, including the suspension of numerous drug companies, leading to a shortage in drug supplies to hospitals. Hospitals were required to use a bioequivalent generic form of a drug for continuing treatment of the patients. Objective: This study assessed the International Normalized Ratio (INR) score for the patients who were switched from Coumadin® (Bristol-Myers Squibb Pharma Company), brand-name warfarin, to a generic form of warfarin in the anticoagulant clinic due to the shortage of Coumadin® during the COVID-19 pandemic. Materials and Methods: A retrospective, cross-sectional chart review study was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. Patients who switched from Coumadin® to generic warfarin from February 2020 to February 2021 were included. This study compared the brand-name and generic forms of warfarin to determine their effectiveness and if the generic form can be used as a therapeutic equivalent. All the data were collected from the electronic health records in KAMC. Each patient file was reviewed for the INR results before and after the switch of warfarin to determine if there was a mean difference between the two variables. Results: In total, 2,197 patients’ medical records were reviewed, yielding 15,499 INR values. The majority (n = 1,362, 80.4%) of the 1,709 mechanical valve INRs were low (INR < 2.1), and 10,697 (77.5%) of the non-mechanical valve INR values were low (INR < 1.6). The Wilcoxon two-sample test was used to evaluate the change in the INR value before and after the switch. The results demonstrate that there is a statistical significance between the effectiveness of Coumadin and generic warfarin. The P values were 0.026 and <0.0001 for the mechanical valve group and the non-mechanical valve group, respectively. Conclusion: The findings of this study indicate that there is a significant difference between the effectiveness of Coumadin and generic warfarin.

Construction of warfarin population pharmacokinetics and pharmacodynamics model in Han population based on Bayesian method

The purpose of this paper is to study the genetic polymorphisms of related gene loci (CYP2C9*3, VKORC1-1639G > A) based on demographic and clinical factors, and use the maximum a posterior Bayesian method to construct a warfarin individualized dose prediction model in line with the Chinese Han population. Finally, the built model is compared and analyzed with the widely used models at home and abroad. In this study, a total of 5467 INR measurements are collected from 646 eligible subjects in our hospital, and the maximum a posterior Bayesian method is used to construct a warfarin dose prediction that conforms to the Chinese Han population on the basis of the Hamberg model. The model is verified and compared with foreign models. This study finds that body weight and concomitant use of amiodarone have a significant effect on the anticoagulant effect of warfarin. The model can provide an effective basis for individualized and rational dosing of warfarin in Han population more accurately. In the performance of comparison with different warfarin dose prediction models, the new model has the highest prediction accuracy, and the prediction percentage is as high as 72.56%. The dose predicted by the Huang model is the closest to the actual dose of warfarin. The population pharmacokinetics and pharmacodynamics model established in this study can better reflect the distribution characteristics of INR values after warfarin administration in the Han population, and performs better than the models reported in the literature.

CO5 Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Cancer: A Target Trial Emulation From SEER-Medicare Database

CO5 Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Cancer: A Target Trial Emulation From SEER-Medicare Database

Evaluation of the use and efficacy of prothrombin complex concentrates in patients presenting to the emergency department with warfarin

Aims: Warfarin administration has been a standard treatment for preventing thromboembolism in patients with atrial fibrillation prosthetic heart valves for many years. It is one of the leading drugs implicated in emergency room visits for adverse drug reactions. Because of a narrow therapeutic window, as many as 3% to 7% of patients taking warfarin are at risk of significant, life-threatening bleeding, and it is generally considered that this requires rapid and complete warfarin reversal. Although there are treatments such as vitamin K and fresh frozen plasma to reverse the effects of warfarin, the most effective method involves using prothrombin complex concentrates (PCC). This study aims to evaluate the use and efficacy of PCC in patients with warfarin-induced bleeding in the emergency department. Methods: The patients receiving PCC for warfarin reversal in the emergency department between January 1, 2019 – April 1, 2021, were identified from the hospital's electronic database. Demographic data, reasons for warfarin use, PCC indications, INR values before and after PCC, and mortality of the patients were evaluated. The four-factor PCC dose was determined according to the patient's body weight, admission INR level, and target INR level. The study was conducted with 73 patients. Results: The mean age of the patients was 69.3 ± 15.5 years. The female/male ratio was 1/1.5. The most common PCC indications were gastrointestinal bleeding (32.9%), urogenital bleeding (23.3%), epistaxis (12.3%), and urgent surgical need (12.3%), respectively. The median international normalized ratio (INR) before and after treatment with PCC was 9.2 (min-max 2.1-11.8) and 1.8 (min-max 1.0-4.6). The mean dose of PCC was 1500 IU (min-max 750-3250 IU). In addition to PCC, all patients received vitamin K; 17.8% received erythrocyte suspension, and 10.9% received fresh frozen plasma. There were no PCC-related complications in the emergency department. While 38.4% of the patients consulted the inpatient services after the emergency department, 5.5% were referred to an external center, and 56.2% were discharged from the emergency department after successful treatment. 26% of the patients were followed in the intensive care unit. No patient died in the emergency department. However, in-hospital mortality was 5.5%. Conclusion: Four-factor PCC is an effective and safe treatment for reversing warfarin-associated bleeding.

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Cancer: A Target Trial Emulation from SEER-Medicare Database

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Cancer: A Target Trial Emulation from SEER-Medicare Database

Effects of Salvianolate Injection on the Pharmacodynamics and Pharmacokinetics of Warfarin in Rats In vivo

Background:: Both Salvianolate Injection and warfarin are widely prescribed in patients with cardiovascular diseases, but the interaction between them is unknown and needs to be investigated. Objective:: This research aims to study the effects and mechanism of Salvianolate Injection on the pharmacodynamics and pharmacokinetics of warfarin in rats. Methods:: Male Wistar rats were intraperitoneally injected Salvianolate Injection (18 mg/kg) with or without oral administration of warfarin (0.2 mg/kg). A coagulation analyzer evaluated prothrombin time (PT) and activated partial thromboplastin time (APTT). International normalized ratio (INR) was calculated based on PT. UPLC-MS/MS combined with a chiral column was used to separate and measure the plasma concentration of R-warfarin and S-warfarin. Agilent SB-C18 column (1.8 μm, 2.1 mm × 50 mm) was used for separation, column temperature at 20°C. The isocratic mobile phase was acetonitrile-aqueous ammonium acetate (5 mM, pH 4) at a flow rate of 0.2 mL/min and 11.5 min for each injection. Pharmacokinetic parameters were calculated using DAS 2.0 software. Results:: Salvianolate Injection increased PT and INR (p < 0.05), while APTT was unaffected (p > 0.05). Compared with the warfarin group, the co-administration of Salvianolate Injection and singledose warfarin enlarged PT and INR (p < 0.05). Similar increases in pharmacokinetic parameters of R-warfarin and S-warfarin, including Cmax, AUC0-t, AUC0-∞, t1/2, and CL/F (p < 0.05), were observed in the co-administration group. A steady-state study of warfarin indicated that PT and INR in the coadministration group are longer than those in the warfarin group (p < 0.05). On days 7th and 8th of warfarin treatment (two and three days after Salvianolate Injection treatment), the plasma concentration of R-warfarin increased by 47.22% and 50.16% (p < 0.05), and plasma concentration of Swarfarin increased by 32.39% and 45.99% (p < 0.05), respectively. Conclusion:: Salvianolate Injection exhibits an anticoagulation effect in rats. Salvianolate Injection can enhance the anticoagulant effect of warfarin by slowing metabolism and increasing the concentration of both enantiomers. These results suggest that the combination of Salvianolate Injection and warfarin should be avoided or closely monitored in case of increasing bleeding risk.