Background Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesised systematically, nor has the quality of evidence been considered. We synthesised systematic review evidence of cardiovascular toxicity of individual targeted agents. Methods We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (PROSPERO CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes, based on statistical significance, study quality and size. Results From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including: high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (ATE; includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade ATE for trastuzumab, and all-grade ATE for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction (LVEF) decline or congestive heart failure (CHF) for bevacizumab and trastuzumab, and all-grade LVEF decline/CHF for pazopanib and sunitinib; and all-grade QTc interval prolongation for vandetanib. Conclusion Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.

Recent years have seen developments in distributed ledger technologies, such as blockchain, that have led to significant growth in the number and type of digital assets available. In this article we review the current practice of the small number of firms globally reporting digital assets on their financial statements. We then assess potential treatments under current GAAP, namely as intangibles, inventory or financial instruments. Finally, we provide policy advice to standard setters, with a call to either develop a new stand‐alone standard or to amend the definition of financial instruments to include cryptocurrencies, to allow greater comparability and understandability in firms’ reporting.Recent years have seen significant growth in the number and type of digital assets available. We review the current practices of firms reporting digital assets. We then assess potential treatments under current GAAP. Finally, we provide policy advice to standard setters, with a call to either develop a new stand‐alone standard or to amend the definition of financial instruments.

IntroductionThe introduction of targeted therapies for cancer has contributed to dramatic improvements in patient survival. Nevertheless, several targeted therapies have been associated with ‘off-target’ adverse effects, based on varying levels of evidence. To date, this evidence has not been systematically synthesised. We will synthesise published systematic review evidence of cardiovascular toxicity associated with targeted cancer therapies.Methods and analysisWe will include systematic reviews of randomised controlled trials and observational studies that report on cardiovascular outcomes for individual agents. We will identify systematic reviews by applying predeveloped, standardised search strategies within Embase, Medline and Cochrane Central. Two independent reviewers will identify reviews published up to 31 December 2016 using predefined eligibility criteria. They will resolve ambiguous cases through consensus, arbitrated by a third reviewer if required. The reviewers will extract and report data according to methodological guidelines for overviews provided by the Cochrane Collaboration, Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. They will assess the quality of included reviews by applying the Assessment of Multiple Systematic Reviews tool. They will judge the quality of evidence in included reviews based on their assessment of bias and incorporation into the interpretation of findings. In synthesising the evidence, we will classify agents based on systematic review evidence of toxicity (sufficient, probable, possible or indeterminate) for specific cardiovascular outcomes (congestive heart failure, myocardial infarction, ischaemic heart disease, left ventricular ejection fraction decline, cerebrovascular disease, pulmonary embolism, thrombosis and hypertension). This will provide clinicians and patients with an accessible synthesis based on robust methodology.Ethics and disseminationEthics approval is not required for overviews. We will conduct the study in collaboration with consumer representatives. We will submit results for peer-review publication, and disseminate them through established clinical and consumer networks.PROSPERO registration numberCRD42017080014.