In patients presenting with acute coronary syndromes and multivessel coronary artery disease, the question of whether to undertake a strategy of complete revascularisation in cases in which percutaneous coronary intervention (PCI) is performed routinely on non-culprit lesions (in addition to the culprit lesion) or whether to restrict PCI only to the culprit lesion is a common dilemma. The Complete Revascularisation Trialists' Collaboration aimed to determine, based on the totality of data from randomised trials, the effect of a complete revascularisation strategy on major cardiovascular events and whether it reduces cardiovascular death.

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce albuminuria and risk of progression of chronic kidney disease. Non-steroidal mineralocorticoid receptor antagonists (MRA) have similar effects in patients with type 2 diabetes with chronic kidney disease. We aimed to assess efficacy and safety of the novel MRA balcinrenone combined with the SGLT2 inhibitor dapagliflozin in a randomised controlled trial.

Coagulation factor XI (FXI) inhibitors can reduce the incidence of thrombosis without increasing bleeding risk. FXI is activated by factor XIIa (FXIIa) or thrombin. REGN7508Cat is an antibody that binds to the FXI catalytic domain, blocking both its activity and activation by FXIIa and thrombin. REGN9933A2 binds to the FXI apple 2 domain and blocks FXI activation by FXIIa. We aimed to compare the efficacy and safety of REGN9933A2 and enoxaparin, with apixaban as an exploratory comparator, and REGN7508Cat and enoxaparin for venous thromboembolism prevention.

Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment.

Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity.

We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can activate the renin-angiotensin system (RAS) and potentially undermine the cardiorenal benefits of these therapies. Paradoxically, new-generation amylin-based therapies, such as CagriSema, showed substantial blood pressure reductions in phase 3 trials. Beyond amylin's weight loss-mediated effects, we hypothesise that concurrent use of RAS inhibitors (angiotensin-converting enzyme [ACE] inhibitors or angiotensin-receptor blockers) redirects amylin-induced RAS activation towards the protective alternative RAS pathway, which is characterised by vasodilatory, anti-inflammatory, and antiproliferative effects via Mas receptors, potentially explaining part of their therapeutic benefit and cardioprotective and renoprotective potential. To test this, we propose: (1) preclinical studies investigating amylin-RAS interactions with or without RAS blockade; (2) post-hoc analyses of phase 2/3 trials stratified by RAS inhibitor use; (3) biomarker studies monitoring renin, aldosterone, angiotensin-(1-7), and ACE2; and (4) mechanistic human studies prospectively assessing cardiovascular-kidney metabolic effects by RAS inhibitor status. These suggestions aim to determine whether RAS inhibition enhances the overall efficacy of amylin-based therapies, and whether RAS blockers should be strongly recommended in patients receiving them.