Anticoagulation Strategies in Patients With Cancer: JACC Review Topic of the Week

Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.     

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia

Background

Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice.

Cardiac Implantable Electronic Devices in Patients With Left Ventricular Assist Systems

Recent progress and evolution in device engineering, surgical implantation practices, and periprocedural management have advanced the promise of durable support with left ventricular assist systems (LVAS) in patients with stage D heart failure. With greater uptake of LVAS globally, a growing population of LVAS recipients have pre-existing cardiac implantable electronic devices (CIEDs). Strategies for optimal clinical management of CIEDs in patients with durable LVAS are evolving, and clinicians will increasingly face complex decisions regarding implantation, programming, deactivation, and removal of CIEDs. Traditional decision-making pathways for CIEDs may not apply to LVAS-supported patients, as few patients die of arrhythmic causes and many arrhythmias may be well tolerated. Given limited data, treatment decisions must be individualized and made collaboratively among electrophysiologists, advanced heart failure specialists, and patients and their caregivers. Large, prospective, well-conducted studies are needed to better understand the contemporary utility of CIEDs in patients with newer-generation LVAS.     

Oral Anticoagulation in Patients With Liver Disease

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are “auto-anticoagulated” and thus protected from thrombotic events. Warfarin and non–vitamin K–antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.     

Retraction: Radio frequency triggered curcumin delivery from thermo and pH responsive nanoparticles containing gold nanoparticles and its in vivo localization studies in an orthotopic breast tumor model

Retraction of ‘Radio frequency triggered curcumin delivery from thermo and pH responsive nanoparticles containing gold nanoparticles and its in vivo localization studies in an orthotopic breast tumor model’ by N. Sanoj Rejinold et al., RSC Adv., 2014, 4, 39408–39427, DOI: 10.1039/C4RA05727A.

We, the named authors, hereby wholly retract this RSC Advances article due to duplication of images in Fig. 9–12, 15, 18 and 19, which affect the reliability of the data and the overall conclusions presented in the published article.Signed: N. Sanoj Rejinold, Reju George Thomas, Muthunarayanan Muthiah, K. P. Chennazhi, In-Kyu Park, K. Manzoor and R. Jayakumar, 24th July 2020.Yong Yeon Jeong was contacted but did not respond.Retraction endorsed by Laura Fisher, Executive Editor, RSC Advances.     

Incidence and Outcomes of Pneumonia in Patients With Heart Failure

BackgroundThe incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).ObjectivesThis study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials.MethodsThe authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro–B-type natriuretic peptide).ResultsIn PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58).ConclusionsThe incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor–Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711)