Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum.

Chronic kidney disease (CKD) is a global health problem and an independent risk factor for cardiovascular morbidity and mortality. Despite evidence-based therapies significantly improving cardiovascular mortality outcomes in the general population and those with non-dialysis-dependent CKD, this risk reduction has not translated to patients with end-stage kidney disease (ESKD). Absent from all major antiplatelet trials, this has led to insufficient safety data for P2Y12 inhibitor prescriptions and treatment inequity in this subpopulation. This review article presents an overview of the progression of research in understanding antiplatelet therapy for ischaemic heart disease in patients with advanced CKD (defined as eGFR <30 mL/min/1.73 m2). Beyond trial recruitment strategies, new approaches should focus on registry documentation by CKD stage, risk stratification with biomarkers associated with inflammation and haemorrhage and building a knowledge base on optimal duration of dual and single antiplatelet therapies.

What is the context? Patients with kidney disease are more likely to experience a heart attack than those without.Those with advanced kidney disease have a higher risk of death following a heart attack.Over the past two decades, advances in treatment following a heart attack have reduced the risk of death, however this has not translated to those with advanced kidney disease.Progression of kidney disease influences antiplatelet (e.g. clopidogrel) treatment efficacy.What is new?This contemporary review analyses registry and trial data to highlight some of the issues surrounding treatment inequity in patients with advanced kidney disease.This article describes potential mechanisms by which progression of kidney disease can influence clotting, bleeding and antiplatelet treatments.What is the impact?Further research into antiplatelet therapy for patients with advanced kidney disease is required.Registry and trial data can improve upon classification of kidney disease for future research.Future trials in antiplatelet therapy for advanced kidney disease are anticipated.

Digital endpoints in clinical trials: emerging themes from a multi-stakeholder Knowledge Exchange event.

BACKGROUND: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people's chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person's health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. METHODS: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day's discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. RESULTS: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. CONCLUSIONS: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.

Meta-analysis of echocardiographic quantification of left ventricular filling pressure.

AIMS: The clinical reliability of echocardiographic surrogate markers of left ventricular filling pressures (LVFPs) across different cardiovascular pathologies remains unanswered. The main objective was to evaluate the evidence of how effectively different echocardiographic indices estimate true LVFP. METHODS AND RESULTS: Design: this is a systematic review and meta-analysis. DATA SOURCE: Scopus, PubMed and Embase. Eligibility criteria for selecting studies were those that used echocardiography to predict or estimate pulmonary capillary wedge pressure or left ventricular end-diastolic pressures. Twenty-seven studies met criteria. Only eight studies (30%) reported both correlation coefficient and bias between non-invasive and invasively measured LVFPs. The majority of studies (74%) recorded invasive pulmonary capillary wedge pressure as a surrogate for left ventricular end-diastolic pressures. The pooled correlation coefficient overall was r = 0.69 [95% confidence interval (CI) 0.63-0.75, P < 0.01]. Evaluation by cohort demonstrated varying association: heart failure with preserved ejection fraction (11 studies, n = 575, r = 0.59, 95% CI 0.53-0.64) and heart failure with reduced ejection fraction (8 studies, n = 381, r = 0.67, 95% CI 0.61-0.72). CONCLUSIONS: Echocardiographic indices show moderate pooled association to invasively measured LVFP; however, this varies widely with disease state. In heart failure with preserved ejection fraction, no single echocardiography-based metric offers a reliable estimate. In heart failure with reduced ejection fraction, mitral inflow-derived indices (E/e', E/A, E/Vp, and EDcT) have reasonable clinical applicability. While an integrated approach of several echocardiographic metrics provides the most promise for estimating LVFP reliably, such strategies need further validation in larger, patient-specific studies.

Autoinflammatory constrictive pericarditis and chronic myelomonocytic leukaemia: when one speciality is not enough.

We present a case of constrictive pericarditis with concomitant blood and bone marrow appearances of chronic myelomonocytic leukaemia (CMML). Despite surgical treatment with pericardiectomy, the patient deteriorated into multiorgan failure. Pericardial histology disclosed a typical inflammatory picture with no evidence of monocytic or malignant infiltrate. Following intensive collaboration between cardiologists, haematologists and rheumatologists via daily email exchanges, a diagnosis was reached of autoinflammatory constrictive pericarditis with a non-infiltrative coexisting CMML. The key to achieving a rapid and sustained response was a trial of high-dose steroids followed by intravenous immunoglobulins. This achieved restoration of cardiac function, resolution of symptoms and near normalisation of inflammatory markers. A diagnosis of concurrent CMML was confirmed at 3 months. The patient remains well, taking colchicine and steroids.