Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review and meta-analysis protocol.

INTRODUCTION: Whether bisphosphonates and RANKL inhibitors play a novel role in delaying cardiovascular calcification is unknown. Their action on regulatory enzymes in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism, may be a novel therapeutic target to manage coronary artery disease (CAD). Such therapies may particularly be relevant in those for whom traditional cardiovascular therapies are no longer sufficient to control disease progression. METHODS AND ANALYSIS: We will perform a systematic review which aims to synthesise evidence regarding whether use of bisphosphonates or use of the RANKL inhibitor denosumab delays coronary artery calcium (CAC) progression. Eligible studies will include longitudinal studies investigating CAC progression in patients aged >18 years taking either a bisphosphonate or denosumab compared with those who do not. Embase, MEDLINE and Cochrane will be searched using prespecified search terms. Studies will be screened by title and abstract independently and then in full to determine suitability for inclusion in the review. Extracted data will include that relating to study and participant characteristics. The primary outcome will be the CAC score. Secondary outcomes will include aortic and carotid artery calcification. Meta-analysis will be performed if sufficient data are available. ETHICS AND DISSEMINATION: This study does not require ethics as it is a systematic review of the literature. The results of the review described within this protocol will be distributed via presentations at relevant conferences and publication within a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: The systematic review pertaining to this protocol is registered with PROSPERO (Registration ID: CRD42022312377).

Investigating the association between blood transfusion and clinical outcomes in patients with acute coronary syndromes: a data linkage approach to Patient Blood Management.

BACKGROUND: The appropriateness of the use of blood transfusion in patients with acute coronary syndromes (ACS) remains contested. In general, studies addressing this issue were based on data from clinical trials, registries, or electronic medical records, and were conducted across different settings. Our study aimed to use a linked patient blood management data system from existing hospital databases to examine the association between blood transfusion and in-hospital mortality, length of stay (LOS) and readmission rates among patients with ACS, and to investigate this relationship at different haemoglobin (Hb) concentrations. MATERIALS AND METHODS: This was a retrospective observational study of patients admitted to participating hospitals between 1st January 2014 to 31st December 2017 with ACS recorded as primary diagnosis. Admission and nadir Hb concentrations were categorised as ≤100 g/L and >100 g/L. Generalised estimating equations were used to investigate the association between transfusion and clinical outcomes, while accounting for the correlation of multiple admissions from the same patients across hospitals over the study period. RESULTS: Of the 9,952 admissions included, blood transfusions occurred in 705 (7.1%). In unadjusted analyses, transfusion was associated with an increased risk of in-hospital mortality (OR: 2.97; 95% CI: 2.14-4.13) and an average LOS 3.55 (95% CI: 3.38-3.72) times longer. After adjusting for demographic and clinical factors, transfusion was associated with an increased risk of in-hospital mortality when Hb >100 g/L. Transfusion was not associated with the risk of readmission. DISCUSSION: The effect of transfusion on in-hospital mortality was largely dependent on the pre-transfusion Hb concentration. When Hb was >100 g/L transfusion was associated with increased mortality, whereas when Hb ≤100 g/L no association was observed.