Direct Oral Anticoagulants Research Articles

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding

Monitoring the efficiency of reversal on anti-Xa direct oral anticoagulants using point-of-care viscoelastic testing

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually “blinded” with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5mg BID or rivaroxaban 10mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14-p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

Dose-adjusted direct oral anticoagulants (DOACs) in patients with acute leukemia: experience of a tertiary cancer care center.

Dose-adjusted direct oral anticoagulants (DOACs) in patients with acute leukemia: experience of a tertiary cancer care center.

Prospective study on the impact of different antithrombotic therapies on subclinical leaflet thickening and its temporal dynamics in transcatheter aortic valves—The NOTION-4 trial

Transcatheter aortic valve replacement (TAVR) has become the standard-of-care treatment for a majority of patients with severe, symptomatic aortic stenosis. The post-procedural anti-thrombotic therapeutic management is still a topic of debate and could affect the incidence of HALT, a phenomenon which can be assessed by four-dimensional computed tomography (4DCT). The NOTION-4 trial is a randomized controlled trial comprising TAVR patients with no indication for oral anticoagulant (OAC) therapy, comparing lifelong single anti-platelet therapy (standard arm) versus early 3-month direct oral anticoagulant (DOAC) therapy followed by single anti-plateletet therapy (experimental arm). The incidence of HALT and clinical endpoints will be evaluated in both groups at 3 months, 1 year and 5 years after randomization. The primary endpoint is the number of patients with at least one bioprosthetic aortic valve leaflet with HALT as assessed by cardiac 4DCT imaging at 1 year. The trial is powered for superiority testing and started enrollment in 2021. In total, 324 patients will be included. The last patient is expected to be enrolled by the end of 2024 and the primary endpoint is to be presented in 2026. The NOTION-4 trial aims to study whether an early 3-month DOAC therapy after TAVR can result in a sustained lower incidence of HALT in transcatheter aortic valves. This trial holds the potential to give valuable insights into whether early OAC therapy should be integrated in future guidelines for post-TAVR anti-thrombotic therapeutic management. NOTION-4, ClinicalTrials.gov ID NCT06449469, https://clinicaltrials.gov/study/NCT06449469.

6511 Provider Opinions on Holding Antiplatelet and Anticoagulant Drugs Prior to Thyroid Nodules FNA Biopsy: A Survey Study

Abstract Disclosure: M.D. Lundholm: None. P.P. Rao: None. Objective: It is thought that anticoagulant (AC) or antiplatelet (AP) therapy at the time of thyroid nodule fine needle aspiration biopsy (TNFNAB) may increase the risk of non-diagnostic results and post-procedure hematomas. However, interrupting a patient’s AC or AP can lead to procedural delays or have thrombotic consequences. Since there is currently no consensus on whether or not to hold these medications, this study aims to survey the expertise of our providers across multiple specialties. Methods: A survey was sent out to Cleveland Clinic providers who have performed TNFNABs for patients with an active prescription for AC or AP since 2010. Providers were asked if they routinely held a number of blood thinner medication classes and included a free response section for open-ended comments. Results: The survey responses represented 60 providers (of 68 invited, 88% response rate). Respondents were 51.7% medical endocrinologists, 30% interventional radiologists, 13% surgical endocrinologists, and 5% ENTs. Of respondents, 13.3% held aspirin 81 mg, 15.0% held aspirin 325 mg, 41.7% held other antiplatelet agents, 73.3% held warfarin, 43.3% held direct oral anticoagulants (DOACs), and 43.3% held heparin. No department was uniform in practice, with the least agreement (responses closest to 50%) amongst medical endocrinologists. In a subset of 15 providers who have performed ≥100 TNFNABs on patients with AC/AP, a consensus emerged not to hold aspirin at any dose, but there was no agreement in any other AC/AP categories (hold rates ranging 53.5-66.6%). Free response themes reiterated that the main concerns for continuing blood thinners are hematomas and non-diagnostic results. Other comments included consideration of the nodule features such as location as well as strategies used to lower risk for hematomas (i.e., small-gauge needles, ice, holding pressure). A couple responses referred to the Society of Interventional Radiology (SIR) and the International Society on Thrombosis and Haemostasis (ISTH) guidelines which offer INR and platelet goal recommendations prior to any procedure with a low bleeding risk. Discussion: A survey of Cleveland Clinic providers demonstrated that ≥85% continue aspirin therapies prior to TNFNAB. However, there is no such agreement in any other category of AC/AP medication, even amongst the most experienced providers. The closest guidelines available come from SIR and ISTH and rely on recent platelet and/or INR information, which may not be available in routine endocrinology practice. The caveat is that these recommendations are not specific to TNFNAB and do not take into account the nuances of this procedure. Conclusion: There is wide variation in provider opinions and practice patterns regarding AC and AP medications prior to TNFNAB. This highlights the need for further study into the safety and adequacy of TNFNAB performed on uninterrupted AC or AP therapy. Presentation: 6/3/2024

Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: an analysis from the Japan Stroke Data Bank.

Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage admitted within 24 hours after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5-6 at discharge. Of a total 9,810 patients with intracerebral hemorrhage (4,267 females; mean age, 70±15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5-22), 13 (5-26), 15 (5-30), and 13 (6-24), respectively, in the four groups. In multivariable analysis, the pre stroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio, 1.09 [95%confidence interval (CI), 1.06-1.13], with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 [95%CI, 0.98-1.02]) and DOAC group (0.98 [95%CI, 0.95-1.01]) was not. The rate of mRS 5-6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, pre stroke warfarin use was associated with mRS 5-6 (adjusted odds ratio: 1.90 [95%CI, 1.28-2.81], with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 [95%CI, 0.91-1.37]) and DOAC group (1.25 [95%CI, 0.88-1.77]) was not. Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.

Rates and risk factors of bleeding after gastric endoscopic submucosal dissection with continuous warfarin or 1-day withdrawal of direct oral anticoagulants.

The 2017 Japanese guidelines recommend continuing warfarin therapy during the perioperative period or discontinuing direct oral anticoagulants (DOACs) only on the day of endoscopic submucosal dissection for early gastric cancer. However, their safety has not been sufficiently explored. This study aimed to validate this management method. This retrospective, multicenter study analyzed the characteristics and outcomes of patients who underwent gastric endoscopic submucosal dissection between July 2017 and June 2019. The patients were categorized according to the use of warfarin or DOACs. Among the 62 eligible patients, 53 (85%) were male (median age, 76years). Warfarin was used in 10 patients (16%) and DOACs in 52 patients (84%). Fourteen patients taking DOACs (27%) used concomitant antiplatelet agents, with seven patients (13%) continuing treatment at the time of the endoscopic procedure. No postprocedural bleeding occurred in patients receiving warfarin (0%), whereas 10 cases (19%) of bleeding occurred in patients receiving DOACs: rivaroxaban, 0% (0/22); dabigatran, 0% (0/2); edoxaban, 43% (6/14); and apixaban, 29% (4/14). The type of anticoagulant (P<0.01) and continuation of antiplatelet therapy (P=0.02) were risk factors for postprocedural bleeding in patients receiving DOACs. Intraprocedural bleeding requiring transfusion or symptomatic thromboembolic events were not reported. Continuous warfarin therapy is preferred. DOAC withdrawal 1day before a procedure is associated with a high bleeding rate, which may differ for different types of anticoagulants. The continuation of antiplatelet medications in patients receiving DOACs carries a high risk of bleeding and is a future challenge.

Safety of edoxaban for delayed bleeding in gastrointestinal endoscopic procedures with a high risk of bleeding.

There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding. This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations. Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays. The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.

The utility of the dilute prothrombin time in the interpretation of antiphospholipid syndrome testing.

To evaluate the utility of the dilute prothrombin time (DPT) in diagnosing antiphospholipid syndrome (APS), alone and when paired with the dilute Russell viper venom time (DRVVT). Dilute prothrombin time and DRVVT testing was performed on plasma samples spiked with apixaban or rivaroxaban, or depleted of vitamin K-dependent clotting factors. A retrospective analysis of all functional APS testing results over a 44-month period at the University of Chicago Medical Center was performed. In spiking studies, the screening clotting time in the DPT (DPTS) is more sensitive to deficiency of vitamin K-dependent factors than is the screening clotting time in the DRVVT (DRVVTS). The converse is true for factor Xa direct oral anticoagulant (DOAC)-spiked plasma. In a 44-month retrospective analysis, only 2.6% of clinical APS panels showed isolated positivity in the DPT-based system. Comparing the DPT-based system with the DRVVT-based system showed utility in identifying false-positive DRVVT results due to anticoagulation. A DRVVTS/DPTS ratio of 0.785 or lower predicted an international normalized ratio of 1.5 or higher (sensitivity, 86.3%; specificity, 60.4%; likelihood ratio, 2.18). Conversely, a DRVVTS/DPTS ratio of 1.165 or higher was the optimal cutoff for predicting the identification of factor Xa DOAC (sensitivity, 61.8%; specificity, 77.8%; likelihood ratio, 2.78). Within the data set that had full DRVVT and DPT results, parameters were identified that could further improve identification of samples with anticoagulation interference. Dilute prothrombin time lupus anticoagulant assay is rarely the sole laboratory functional evidence for APS, but when combined with the DRVVT, the DPT can serve as an effective screen for common anticoagulant interference.

A-163 Stability of apixaban in Li-heparin plasma stored refrigerated over mint green-top tube separator gel

Abstract Background Apixaban is a factor Xa inhibitor used as a direct oral anticoagulant (DOAC). The laboratory was asked to provide measurements of plasma apixaban in the context of studies regarding interaction of apixaban with other therapeutic drugs. One study involved isolation of plasma from to-be-discarded specimens, where such specimens were those originally collected in mint green-top tubes (Li-heparin tubes containing plasma separator gel), and that had been centrifuged and stored refrigerated for 5 days. Whereas apixaban concentration is known to be stable in refrigerated plasma specimens for up to two weeks, stability of apixaban concentration in plasma stored refrigerated for prolonged periods over plasma separator gel was unknown. Our objective was to examine stability of apixaban in plasma stored refrigerated for 5 days over plasma separator gel. Methods Pharmacy records were reviewed to identify inpatients who were prescribed apixaban, and for whom a mint green-top tube specimen (Becton-Dickinson BD Vacutainer PST Gel and Lithium Heparin, #367961) had been drawn for routine chemistry tests. From such specimens, 500 uL aliquots of plasma were obtained on day 1 (A) and day 5 (B) of storage under refrigeration (4 °C). Apixaban concentrations for A and B were measured by LC-MS/MS and compared. Additionally, short term (1 day) stability of apixaban was examined by comparison of replicate measurements of apixaban in a single spiked pooled purple-top plasma specimen (Becton-Dickinson BD Vacutainer K2 EDTA, #367856), with (C) or without (D) exposure to mint green-top tube separator gel for a 24h refrigeration period. Data analyses were conducted using R (version 4.0.5). Results A total of 21 specimen pairs (A, B) were examined. [Apixaban] ranged from 30-1000 ng/mL. The ratio B/A was 1.007 ± 0.034, consistent with no effect on plasma [apixaban] of refrigerated storage over separator gel between day 1 and day 5 (by paired t-test: p&amp;gt;0.8). Experiments for replicates of (C, D) specimens (n = 4, average [apixaban] = 410 ng/mL) gave D/C ratio of 1.009 ± 0.019, consistent with no effect on plasma [apixaban] of short term (1 day) refrigerated storage of plasma over separator gel (by paired t-test: p&amp;gt;0.4). Conclusions For plasma specimens collected and centrifuged in mint-green plasma separator tubes, there was no effect on plasma [apixaban] of refrigerated storage over separator gel for periods of 0-5 days.

Prevention and treatment of cancer-associated thrombosis during chemotherapy

In patients with malignant neoplasms, the incidence of symptomatic venous thromboembolism (VTE) is 4–7 times higher than in the general population. The presence of distant metastases of solid tumors increases the risk of VTE. Most often, VTE develops in pancreatic and stomach cancers. Chemotherapy increases the risk of VTE development. Low-molecular-weight heparin and direct oral anticoagulants are used for the treatment of VTE in patients receiving chemotherapy.Prior to the start of chemotherapy, it is necessary to assess the risk of VTE development using the Khorana risk score. Outpatient patients with high-risk cancer (Khorana score &gt;3 before the start of a new systemic chemotherapy regimen) may be prescribed thromboprophylaxis.

Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry

ObjectiveTo evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).DesignObservational cohort analysis based on a...

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.

An Evaluation of the Safety of Half-Dose Direct Oral Anticoagulants Following Total Joint Arthroplasty: A Pilot Study.

Background Total joint arthroplasty (TJA) patients on preoperative anticoagulation therapy present a challenge for adult reconstructionsurgeons. The goal in managing such patients is to limit bleeding complications associated with administering the medications while preventing medical complications from withholding them. At our institution, we began a protocol in 2017 that utilizes a half-dose direct oral anticoagulant (DOAC) regimen for one week followed by resuming of the full-dose regimen in select patients who underwent TJA. This study investigated the 90-day safety profile associated with this protocol compared to previous literature. Methodology A retrospective review of 898 patients from a single institution was conducted including allpatients receiving a half-dose DOAC protocol for one week followed by resuming of the full-dose regimen after total knee and total hip arthroplasty between 2017 and 2022. Data were collected on patient demographics, type of surgery, and DOAC dosage. Ninety-day complications were collected and separated into reduced dose complications of DOAC (such as cerebrovascular accidents (CVAs) or venothrombotic events (VTEe)) and DOAC therapy-related complications (including wound and bleeding complications). Results In the total hip arthroplasty (THA) subgroup (n = 396, 44.10%), there were four major VTE occurrences, aligning with therange seen in historical protocols. Deep vein thrombosis (DVT) and pulmonary embolism (PE) incidents were three and one, respectively, both within the historical range. In the total knee arthroplasty (TKA) subgroup of 502 (55.90%) patients, there were seven major VTE events, with five DVTs and two PEs, also aligning with historical ranges. Medical complications in the THA group included no CVA events and one myocardial infarction, with the latter slightly higher than the historical range. In the TKA group, there were two medical complications, both being CVAs. Regarding bleeding complications, THA patients showed four major bleeding incidents, two blood transfusions, and two hemorrhages, with these numbers comparable to or lower than historical ranges. There were seven minor bleeding events. For TKA, there were two major bleeding events, two blood transfusions, no hemorrhages, and five minor bleeding events. Wound complications in THA included five surgery-related complications, two cases of wound dehiscence, and three infections. TKA patients experienced 17 surgery-related complications, six cases of wound dehiscence, and 11 infections. Conclusions This study suggests that the half-dose DOAC protocol in patients undergoing TJA is non-inferior to historical full-dose DOACprotocolswarranting further investigation to generalize across broader populations.

Real-world antithrombotic strategies in patients with atrial fibrillation and recently developed acute coronary syndrome

BackgroundThe antithrombotic strategy for patients with atrial fibrillation (AF) and coronary artery disease following percutaneous coronary intervention is shifting towards less intensive. Nevertheless, for patients with AF and acute coronary syndrome (ACS), an optimal antithrombotic strategy is yet to be established. Methods and resultsWe conducted a multi-center cohort study involving 146 Japanese centers that had prospectively registered 460 patients with AF and ACS followed for 2 years. Primary endpoint was the composite of thrombotic and bleeding events, and secondary endpoints included heart failure hospitalization. At the time of study registration, 86% of participants had received direct oral anticoagulants (DOACs) and 75% had received aspirin-based triple antithrombotic therapy (TAT) between March 2017 and August 2019. Apixaban was the most frequently used DOAC (29%). While the proportion of anticoagulants did not change according to the time course, the intensity of antiplatelets significantly attenuated over time (dual antiplatelet at baseline: 75%, and at 2-years: 7%). The cumulative incidence of the primary outcome measure was similar in patients with warfarin and DOACs. However, the risk of heart failure hospitalization was significantly higher in those with warfarin compared to DOACs (Hazard ratio: 2.8, 95% confidence interval: 1.1-5.8, p=0.022). ConclusionsThe present findings suggest the appropriate optimization of antithrombotic medication balancing in patients with AF and ACS in Japan by reducing the intensity of antiplatelets during the study period.

Anticoagulation Therapy Timing in patients with Atrial Fibrillation after Acute and Chronic Subdural Haematoma (ATTAACH): a pilot randomised controlled trial

IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding...

The Effects of Removing the Requirement for Prior Reimbursement Approval on Anticoagulant Use in Ireland: A Cross-Sectional Study.

Prior approval for reimbursement is a policy of cost containment while ensuring oversight and governance of medicines. It has been employed in Ireland to address financial challenges due to the shift from warfarin to direct oral anticoagulants (DOACs). Studies assessing the effectiveness of this policy are limited. Thus, we aimed to examine the effectiveness of prior approval for reimbursement of DOACs (apixaban, rivaroxaban) as a cost containment policy in Ireland. The Irish Health Service Executive-Primary Care Reimbursement Service database was used in this cross-sectional study. We examined the prescribing frequencies and associated costs of the oral anticoagulants; [(OACs) apixaban, rivaroxaban and warfarin] listed in the top 100 most frequently prescribed drugs, between 2018 and 2021. Time series negative binomial regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020. The prescribing frequency of OACs increased by almost 20% from 2018 to 2021. This study showed there were significant differences in the proportion of OACs prescribed among the Community Drug Schemes. A statistically significant decreased use of apixaban (< 1%, p < 0.05) occurred when prior approval was removed for all DOACs. The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place to minimise any negative effects associated with their use.

Use of antithrombotic therapy and the risk of cardiovascular outcomes and bleeding in cancer patients at the end of life: a Danish nationwide cohort study

BackgroundDespite uncertain benefit-risk profile near the end of life, antithrombotic therapy (ATT) is prevalent in patients with terminal cancer. ObjectivesTo examine adherence and persistence with ATT in terminally ill cancer patients and investigate risks of major and clinically relevant bleeding, venous thromboembolism (VTE), and arterial thromboembolism (ATE) by ATT exposure. MethodsUsing a Danish nationwide cohort of terminal cancer patients, ATT adherence in the year following terminal illness declaration was measured by the proportion of days covered (PDC) by prescription. Discontinuation was defined as a treatment gap of ≥30 days between prescription renewals. One-year cumulative incidences of bleeding complications, VTE, and ATE were calculated, considering the competing risk of death. ResultsDuring 2013-2022, 86 732 terminally ill cancer patients were identified (median age, 75 years; 47% female; median survival, 57 days). At terminal illness declaration, 37.5% were receiving ATT (66.6% platelet inhibitors, 23.0% direct oral anticoagulants, and 10.4% vitamin K antagonists [VKAs]). The mean PDC was 88% (SD, 30%), highest among platelet inhibitor users (mean PDC, 89%) and lowest among VKA users (73%). One-year ATT discontinuation incidence was 7.9% (95% CI, 7.7%-8.1%). Most patients continued ATT until death (74.8% platelet inhibitors, 58.8% direct oral anticoagulants, and 61.6% VKAs). Patients receiving ATT had a lower 1-year VTE risk but higher risks of ATE and major bleeding. ConclusionDespite uncertain benefit-risk profile, most terminally ill cancer patients continue ATT until the end of life. These findings provide insights into current ATT utilization and discontinuation dynamics in the challenging context of terminal illness.

Impact of antiplatelet and anticoagulant drugs on postoperative bleeding in reverse total shoulder arthroplasty

BackgroundThe decision to withdraw or continue antiplatelet and anticoagulant drugs would be balanced on the bleeding risk and the cardiovascular risk. The purpose of this study was to investigate perioperative bleeding in reverse shoulder arthroplasty (RSA) to determine the impact of oral antiplatelet and anticoagulant medications in the absence of drug withdrawal. The hypothesis was that the continuation of antiplatelet and anticoagulant drugs would increase postoperative bleeding but to a limited extent. MethodsDuring the study period, RSA cases were prospectively included and retrospectively reviewed. Cases of revision for arthroplasty, proximal fracture, and cemented stem fixation were excluded. Cases with dual therapy of aspirin and clopidogrel and cases with heparin bridges were also excluded. Age, gender, height, weight, American Society of Anesthesiologists physical status anesthesia risk (ASA), smoking status, preoperative diagnosis, preoperative blood sampling data within one month of surgery (estimated glomerular filtration rate (eGFR), Prothrombin Time-International Normalized Ratio (PT-INR), and activated partial thromboplastin time (APTT)), surgical time, stem length (standard or short stem), and use of tranexamic acid were identified. The presence of diabetes mellitus, rheumatoid arthritis, and hypertension were confirmed as comorbidities. Hemoglobin (Hb) and hematocrit (Ht) values were recorded preoperatively and on the third postoperative day, and estimated blood loss was calculated by Gross formula using the change in preoperative Ht and postoperative day 3 Ht values. Multiple regression models were used to determine predictors of the estimated blood loss. P values less than .05 were considered statistically significant. Results315 RSA cases were analyzed (172 females, a mean age of 77.2 years). The estimated blood loss was 819 ml. The regression equation was statistically significant (P < .0001, R2=0.21), and aspirin, direct oral anticoagulants (DOAC), tranexamic acid, height, and surgery time were statistically significant explanatory variables, showing the predicted changes in bleeding volume for each drug were +283 ml for aspirin, +180 ml for DOAC, and -237 ml for tranexamic acid, respectively. Warfarin and cilostazol were not employed due to P values and Akaike's Information Criterion. Two blood transfusions (without antiplatelet or anticoagulant medications) were administered. One patient on aspirin had a cardiovascular event. ConclusionsThe current study showed that the use of aspirin and DOAC were significant predictors of increased perioperative blood loss, but the amount of increase was in the acceptable range, suggesting that continued antiplatelet and anticoagulant were relatively safe in primary RSA. Administration of tranexamic acid was shown to reduce bleeding significantly.