Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.

Transcatheter aortic valve implantation (TAVI) is a guideline-directed treatment for severe aortic stenosis and degenerated aortic bioprostheses. When new transcatheter heart valve (THV) platforms for TAVI are launched, they should be compared with best-in-practice contemporary THVs for their short-term and long-term performance. The COMPARE-TAVI 1 trial was designed to provide a head-to-head comparison of the SAPIEN 3 or SAPIEN 3 Ultra THVs and the Myval or Myval Octacor THVs.

Coronary artery disease has long been understood through the paradigm of epicardial coronary artery obstruction, causing myocardial ischaemia (a mismatch between myocardial blood supply and demand). However, this model, which focuses on diagnosing and managing coronary artery disease based on ischaemia and cardiovascular events, is flawed. By the time ischaemia manifests, it is often too late for optimal intervention, limiting the effectiveness of treatment options. Despite decades of medical advances, coronary artery disease continues to be a leading cause of morbidity and mortality globally, highlighting the inadequacy of this traditional ischaemic-centric approach. The central limitation of current approaches is the focus on the temporary solutions of restoring myocardial blood flow after obstruction, rather than tackling the underlying disease. Coronary artery disease, caused by atherosclerosis, often results in myocardial infarction through mechanisms that emerge earlier in the progression of disease. The focus of medical care has predominantly been on the recognition of symptoms and treatment of acute events, missing opportunities for early detection and prevention of disease. Billions of dollars in health-care funding continue to be spent on identifying and managing coronary ischaemia; yet, the dominant mechanisms for myocardial infarction are atherosclerotic plaque rupture or erosion and, to a lesser extent, erupted calcified nodules that can emerge at a much earlier stage of the disease. This Commission advocates for a shift in the conceptual framework of coronary artery disease. We suggest reclassifying the condition as atherosclerotic coronary artery disease (ACAD), moving away from the traditional emphasis on ischaemia and acute cardiac events towards a more systematic understanding of atherosclerosis. This reframing will enable the identification and management of the disease much earlier in its course, potentially saving millions of lives worldwide. Risk of ACAD develops over a lifetime, beginning in utero, progressing through childhood and adolescence, and continuing into older age. The early stages of disease, which involve the formation of atherosclerotic plaques, are often undetected. A major shift is needed from acute event-centred care to strategies focused on early diagnosis, prevention, and management of atherosclerosis. In this new framework, ACAD should be recognised across all stages, from the earliest signs of atheroma formation to the advanced stages of disease. Our goals should not just to be to manage symptoms and events but to prevent the disease from developing in the first place and, where possible, reverse its course.

Mixed dyslipidaemia, characterised by elevated concentrations of circulating triglycerides and LDL cholesterol (LDL-C), is associated with an increased risk of atherosclerotic cardiovascular disease. Solbinsiran, a GalNAc-conjugated small interfering RNA targeting hepatic angiopoietin-like protein 3 (ANGPTL3), reduced triglycerides and LDL-C concentrations in a phase 1 study. This study aimed to assess the durability and efficacy of solbinsiran in reducing concentrations of atherogenic lipoproteins in adults with mixed dyslipidaemia.