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Journal of Managed Care & Specialty... Jun 2024The Centers for Medicare and Medicaid Services (CMS) are currently negotiating prices with pharmaceutical manufacturers for the first 10 Part D drugs selected for...
BACKGROUND
The Centers for Medicare and Medicaid Services (CMS) are currently negotiating prices with pharmaceutical manufacturers for the first 10 Part D drugs selected for Medicare drug price negotiation. Non-publicly available data, including the net prices of selected drugs and their therapeutic alternatives, will play a central role in the determination of the maximum fair prices (MFPs).
OBJECTIVE
To estimate price benchmarks involved in the derivation of the starting point of the CMS initial price offer for the 10 drugs selected for Medicare price negotiation.
METHODS
For the 10 drugs selected for negotiation, we reported (1) the list price, (2) the net price after manufacturer discounts, (3) the maximum negotiated price based on the minimum statutory discount, and (4) the ceiling of the MFP, estimated as the lowest of the latter 2. We also estimated net prices for therapeutic alternatives to the selected drugs. Net prices were estimated using peer-reviewed methodology that isolates commercial discounts negotiated between payers and manufacturers from mandatory discounts under government programs. All price benchmarks were estimated at the product level, for 30-day equivalent dosing, using 2021 data.
RESULTS
6 products (apixaban, rivaroxaban, empagliflozin, sacubitril/valsartan, etanercept, and insulin aspart) had therapeutic alternatives with lower net prices, which will be integrated with clinical benefit data in the derivation of initial price offers. The other 4 products (ustekinumab, ibrutinib, sitagliptin, and dapagliflozin) had therapeutic alternatives with higher net prices than the drugs selected for negotiation. For ibrutinib and ustekinumab, prices based on the minimum discounts were considerably lower than the estimated net prices and will likely set the starting point of the initial price offer. For dapagliflozin and sitagliptin, the starting point of the initial price offer will likely resemble their existing net prices.
CONCLUSIONS
Our analyses identify different negotiation scenarios for the first 10 drugs selected for Medicare price negotiation, based on key elements involved in the derivation of the initial price offer. Our analyses can help improve transparency in the negotiation process, because the CMS is not required to reveal the information used in the derivation of price offers.
PubMed: 38905356
DOI: 10.18553/jmcp.2024.24153 -
The Journal of International Medical... Jun 2024The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left...
The gold standard therapy for end-stage heart failure is cardiac transplantation. However, in the face of a donor shortage, a mechanical assist device such as the left ventricular assist device HeartMate 3 (Abbott Laboratories, Abbott Park, IL, USA) serves as bridging therapy to transplantation and/or destination therapy. Current guidelines recommend anticoagulation with a vitamin K antagonist in combination with low-dose aspirin. We herein report a challenging anticoagulation regimen in a patient with a HeartMate 3 in whom systemic anticoagulation with warfarin was not feasible for 4 years because of low compatibility and a rare X-factor deficiency. This is a rare hematological disorder, estimated to affect approximately 1 in every 500,000 to 1,000,000 people in the general population. The patient finally received a modified anticoagulation regimen involving the combination of rivaroxaban and clopidogrel without warfarin. Under this regimen, the patient remained free of thromboembolic complications for 4 years with placement of the left ventricular assist device. This case illustrates that under specific circumstances, long-term absence of warfarin therapy is feasible in patients with a HeartMate 3.
Topics: Humans; Heart-Assist Devices; Warfarin; Thromboembolism; Anticoagulants; Male; Heart Failure; Middle Aged; Clopidogrel; Rivaroxaban; Withholding Treatment
PubMed: 38901839
DOI: 10.1177/03000605241258474 -
Pediatric Blood & Cancer Jun 2024Adolescent venous thromboembolism (VTE) has unique challenges in management, complications, and compliance to anticoagulants. Direct oral anticoagulants (DOACs) have... (Review)
Review
Adolescent venous thromboembolism (VTE) has unique challenges in management, complications, and compliance to anticoagulants. Direct oral anticoagulants (DOACs) have been approved for pediatric VTE management, with an increasing use especially in adolescents. Primary objective is to evaluate the safety and efficacy of DOAC therapy in adolescent VTE. Secondary objectives include adverse events, bleeding events, and overall mortality. A SR protocol was registered in PROSPERO 2022 (CRD42022363928). Databases were searched from inception to September 22, 2022. Studies with children aged 10-18 years, VTE diagnosis, DOAC therapy, randomized control trials (RCTs), cohort, and relevant study types were included. Studies including prophylaxis, non-DOAC therapy, arterial thrombosis, age outliers, non-relevant study types were excluded. Findings are reported in accordance to PRISMA 2020. Nine reports from five studies, published between 2016 and 2022, were included. Rivaroxaban was the most common DOAC. VTE recurrence was 0.02% in the rivaroxaban phase III trial and one patient in the dabigatran phase IIb/III trial. Complete/partial thrombus resolution (CR/PR) was 76.6% in the rivaroxaban phase III trial, and 83.9% in the dabigatran phase IIb/III trial. CR/PR was found to be 68.4% in Dhaliwal et al. study and 83.3% in Hassan et al. study. Major bleeding occurred in one patient. Headache and gastrointestinal symptoms were commonly seen. All-cause mortality occurred in a patient due to cancer progression. DOAC therapy in adolescent VTE had CR/PR in two-thirds of the patients, with low incidence of VTE recurrence and major bleeding. As there are only two randomized controlled trial (RCTs), future adolescents' studies are required to validate our results.
PubMed: 38899913
DOI: 10.1002/pbc.31131 -
Molecules (Basel, Switzerland) Jun 2024Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of...
Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity.
Topics: Humans; Atrial Fibrillation; Heart Failure; Machine Learning; Anticoagulants; Administration, Oral; Male; Female; Aged; Chronic Disease; Warfarin
PubMed: 38893525
DOI: 10.3390/molecules29112651 -
Expert Opinion on Drug Safety Jun 2024Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous...
OBJECTIVES
Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events.
METHODS
Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022.
RESULTS
Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system.
CONCLUSION
Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.
PubMed: 38889295
DOI: 10.1080/14740338.2024.2368815 -
Journal of Pharmacy Practice Jun 2024Describe direct oral anticoagulant (DOAC) level ordering and interpretation practices in association with clinical outcomes at a vascular medicine clinic. This study...
Describe direct oral anticoagulant (DOAC) level ordering and interpretation practices in association with clinical outcomes at a vascular medicine clinic. This study was a retrospective, observational study including patients who had a DOAC level ordered and assessed while on DOAC therapy. The primary outcome was the proportion of DOAC levels within previously reported ranges. Secondary outcomes included thrombotic events, major and clinically relevant non-major bleeding events, and the proportion of DOAC level results which prompted a change in the therapeutic plan. A total of 43 patients who had a DOAC level ordered while on DOAC therapy were included in the study. More patients were on apixaban than other DOACs, and the most common indication for anticoagulation was deep vein thrombosis (DVT) or pulmonary embolism (PE). The most common reasons for ordering DOAC levels included history of gastric bypass (n = 20) and drug-drug interactions (n = 8). Most patients on apixaban had in-range levels (n = 24) compared to out of-range levels (5 patients). More patients on rivaroxaban had a level out-of-range (n = 10) than in-range (n = 4). One patient had a DVT, resulting in hospitalization and change in DOAC therapy. Two patients had bleeding events, with 1 hospitalization and change in DOAC therapy. DOAC level results also prompted changes in therapeutic plans for 9 of the patients. DOAC level results did not always correlate with expected outcomes, and further research is warranted to clarify which clinical situations may benefit from ordering DOAC levels.
PubMed: 38884944
DOI: 10.1177/08971900241262363 -
Research and Practice in Thrombosis and... May 2024The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although...
BACKGROUND
The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although specific and nonspecific hemostatic biotherapies are available, there is a need for small-molecule DOAC reversal agents that are simple and cost-effective to produce, store, and administer.
OBJECTIVES
To identify and characterize a small molecule with procoagulant activity as a DOAC reversal agent.
METHODS
We sought to identify a small procoagulant molecule by screening a chemical library with a plasma clotting assay. The selected molecule was assessed for its procoagulant properties and its ability to reverse the effects of the DOACs in a thrombin generation assay. Its activity as a DOAC reversal agent was also evaluated in a tail-clip bleeding assay in mice.
RESULTS
The hemostatic molecule (HeMo) dose-dependently promoted thrombin generation in plasma, with dose values effective in producing half-maximum response ranging between 3 and 5 μM, depending on the thrombin generation assay parameter considered. HeMo also restored impaired thrombin generation in DOAC-spiked plasma and reversed DOAC activity in the mouse bleeding model. HeMo significantly reduced apixaban-induced bleeding from 709 to 65 μL (vs 43 μL in controls; < .01) and dabigatran-induced bleeding from 989 to 155 μL (vs 126 μL in controls; < .01).
CONCLUSION
HeMo is a small-molecule procoagulant that can counterbalance hemostatic disruption by a thrombin inhibitor (dabigatran) or factor Xa inhibitors (apixaban and rivaroxaban). The compound's effective clot formation and versatility make it a possible option for managing the inherent hemorrhagic risk during DOAC therapy.
PubMed: 38882463
DOI: 10.1016/j.rpth.2024.102426 -
Heart Rhythm Jun 2024There are no clinical trials with head-to-head comparison between the two most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial...
BACKGROUND
There are no clinical trials with head-to-head comparison between the two most commonly used oral anticoagulants (apixaban and rivaroxaban) in patients with atrial fibrillation (AF). The comparative efficacy and safety between these drugs remain unclear, especially among older patients who are at the highest risk for stroke and bleeding.
OBJECTIVE
To compare the risk of major bleeding and thromboembolic events with apixaban versus rivaroxaban in older patients with AF.
METHODS
We conducted a population-based, retrospective cohort study of all adult patients (66 years or older) with AF in Ontario, Canada who were treated with apixaban or rivaroxaban between April 1, 2011 and March 31, 2020. The primary safety outcome was major bleeding and the primary efficacy outcome was thromboembolic events. Secondary outcomes included any bleeding. Rates and hazard ratios (HRs) were adjusted for baseline comorbidities with inverse probability of treatment weighting (IPTW).
RESULTS
This study included 42,617 patients with AF treated with apixaban and 30,725 patients treated with rivaroxaban. After IPTW using the propensity score, patients in the apixaban and rivaroxaban groups were well balanced for baseline values of demographics, comorbidities and medications; both groups had similar mean age of 77.4 years and 49.9% were female. At one year, the apixaban group had reduced risk for both major bleeding with an absolute risk reduction at one year of 1.1% (2.1% vs 3.2%; HR 0.65 [95% CI, 0.59-0.71]) and any bleeding (8.1% vs 10.9%; HR 0.73 [95% CI, 0.69-0.77]) with no difference in the risk for thromboembolic events (2.2% vs 2.2%; HR 1.02 [95% CI, 0.92-1.13]).
CONCLUSIONS
Among AF patients, 66 years or older, treatment with apixaban was associated with reduced risk for major bleeding with no difference in risk for thromboembolic events compared with rivaroxaban.
PubMed: 38878942
DOI: 10.1016/j.hrthm.2024.06.010 -
Thrombosis Research Jun 2024Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K...
BACKGROUND
Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens.
METHODS
A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software.
RESULTS
A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively.
CONCLUSIONS
The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC.
PubMed: 38875846
DOI: 10.1016/j.thromres.2024.109057 -
Breast Disease 2024An 85-year-old Chinese lady presented with a 5-day history of a painless left breast lump. There was no fever, nipple discharge, or history of trauma. She had a past...
An 85-year-old Chinese lady presented with a 5-day history of a painless left breast lump. There was no fever, nipple discharge, or history of trauma. She had a past medical history of atrial fibrillation that was managed with an oral anticoagulant. Mammography demonstrated a dense mass in the upper outer quadrant of the left breast. Ultrasound showed an irregular, heterogeneous 4.7 cm lesion containing debris and cystic spaces with raised peripheral vascularity at the 2 o'clock position, 3 cm from nipple. No internal vascularity was detected. This was managed as a haematoma and rivaroxaban was withheld. Follow-up imaging 3-weeks later showed persistence of the lesion. Bedside needle aspiration yielded haemoserous fluid with immediate reduction in size of the lesion. However, 2 weeks after aspiration, there was recurrence of the 'haematoma'. Multidisciplinary review of the clinical history, examination and imaging was sought, and biopsy of the irregularly thickened areas with vascularity along the periphery of the lesion was recommended. Vacuum-assisted biopsy was performed, and histology returned as metaplastic carcinoma. A recurring 'haematoma' should always prompt a search for a secondary cause, with features such as irregular thickened walls and papillary/nodular components requiring further evaluation with biopsy for histopathological correlation.
Topics: Humans; Female; Hematoma; Breast Neoplasms; Aged, 80 and over; Diagnosis, Differential; Mammography; Metaplasia; Recurrence
PubMed: 38875024
DOI: 10.3233/BD-240006