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The Canadian Journal of Cardiology Jun 2024Individuals with frailty are at higher risk of adverse cardiovascular outcomes and bleeding. The objective of this study was to determine whether the effects of...
BACKGROUND
Individuals with frailty are at higher risk of adverse cardiovascular outcomes and bleeding. The objective of this study was to determine whether the effects of rivaroxaban 2.5mg twice daily in addition to low-dose aspirin are similar among frail compared with non-frail patients with chronic atherosclerotic vascular disease.
METHODS
In the COMPASS trial (ClinicalTrials.gov number NCT01776424), patients with chronic atherosclerotic vascular disease were randomized to receive aspirin 100mg daily, aspirin 100mg daily and rivaroxaban 2.5mg twice daily or rivaroxaban 5mg twice daily. In this post hoc analysis, frailty was evaluated by constructing a cumulative deficit index from 37 diseases, signs, and symptoms. The frailty index for each participant was calculated as the proportion of the 37 deficits exhibited, with values >0.2 considered frail. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HR) and 95% confidence intervals (CI) are reported.
RESULTS
Frailty was present in 13% of the trial population. In non-frail individuals, adding rivaroxaban 2.5mg twice daily to aspirin reduced the primary outcome (HR, 95% CI: 0.69, 0.59-0.80) and mortality (0.75, 0.63-0.90) but increased major bleeding (1.87, 1.51-2.31); however, its effects on the primary outcome (1.06, 0.79-1.42), mortality (1.08, 0.80-1.46) and major bleeding (1.10, 0.71-1.70) were not evident among participants with frailty (respective interaction p-values 0.011, 0.049 and 0.032).
CONCLUSIONS
In adults with chronic atherosclerotic vascular disease, the benefit of adding rivaroxaban 2.5mg twice daily to aspirin was not evident in patients with frailty.
PubMed: 38914270
DOI: 10.1016/j.cjca.2024.06.017 -
Cureus May 2024Intra-abdominal hemorrhage resulting from a ruptured, large hepatic cyst in a polycystic liver disease (PCLD) patient is rare and potentially fatal if not addressed...
Successful Coil Embolization of Active Bleeding From a Replaced Left Hepatic Artery to the Left Gastric Artery Associated With a Traumatic Rupture of a Simple Hepatic Cyst Causing Hemodynamic Instability.
Intra-abdominal hemorrhage resulting from a ruptured, large hepatic cyst in a polycystic liver disease (PCLD) patient is rare and potentially fatal if not addressed promptly. Only a few isolated cases have previously been reported. The usual patient profile consists of elderly patients on anticoagulation, as is demonstrated in our case. Intra-hepatic cysts are broadly classified into congenital, traumatic, infectious, parasitic, and neoplastic. Congenital intra-hepatic cysts can consist of both simple and PCLD, as is outlined in our case. Simple cysts are usually asymptomatic, but occasionally they may achieve larger dimensions and lead to complications such as rupture, obstruction, infection, hemorrhage, and even portal hypertension. We present an uncommon case of a 78-year-old patient with PCLD on rivaroxaban who presented initially with diffuse abdominal pain, distension, and progression into hemodynamic instability. A computerized tomography (CT) scan revealed a ruptured left hepatic lobe cyst, causing hemoperitoneum and resulting in an acute abdomen. This case was complicated by the patient's anticoagulation status and anomalous hepatic vasculature pattern. Interventional radiology (IR) successfully identified the aberrant bleeding vessel and stopped the active extravasation with super-selective coil embolization.
PubMed: 38910654
DOI: 10.7759/cureus.60907 -
Scientific Reports Jun 2024The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants... (Observational Study)
Observational Study
The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants to such patients because of possible harm. The effects of frailty on anticoagulant therapy in older Japanese patients with nonvalvular atrial fibrillation (NVAF) are unclear. Herein, we prescribed rivaroxaban to Japanese patients with NVAF and monitored for a mean of 2.0 years. The primary endpoint was stroke or systemic embolism. The secondary endpoints were all-cause or cardiovascular death, composite endpoint, and major or non-major bleeding. Frailty was assessed using the Japanese long-term care insurance system. A multiple imputation technique was used for missing data. The propensity score (PS) was obtained to estimate the treatment effect of frailty and was used to create two PS-matched groups. Overall, 5717 older patients had NVAF (mean age: 73.9 years), 485 (8.5%) were classified as frail. After PS matching, background characteristics were well-balanced between the groups. Rivaroxaban dosages were 10 and 15 mg/day for approximately 80% and the remaining patients, respectively. Frailty was not associated with the primary endpoint or secondary endpoints. In conclusion, frailty does not affect the effectiveness or safety of rivaroxaban anticoagulant therapy in older Japanese patients with NVAF.Trial registration: UMIN000019135, NCT02633982.
Topics: Humans; Atrial Fibrillation; Aged; Male; Female; Frailty; Rivaroxaban; Aged, 80 and over; Anticoagulants; Japan; Stroke; Frail Elderly; Hemorrhage; Factor Xa Inhibitors; East Asian People
PubMed: 38909144
DOI: 10.1038/s41598-024-65237-4 -
Indian Journal of Pediatrics Jun 2024
PubMed: 38907863
DOI: 10.1007/s12098-024-05191-1 -
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