Daily Cardiology Research Analysis

BACKGROUND: Reducing LDL cholesterol prevents atherosclerotic cardiovascular disease (ASCVD) events. The aim of this study was to evaluate the LDL cholesterol-lowering efficacy of a fixed-dose combination (FDC) of obicetrapib, a CETP inhibitor, and ezetimibe. METHODS: This randomised, double-blind trial across 48 US sites including hospitals, private and group practices, and independent research centres included participants at least 18 years old with pre-existing or high risk for ASVCD or heterozygous familial hypercholesterolaemia with LDL cholesterol concentrations of 1·8 mmol/L (70 mg/dL) or greater despite maximally tolerated lipid-lowering therapy excluding ezetimibe, or having statin intolerance. Participants were randomly assigned (1:1:1:1) to obicetrapib 10 mg plus ezetimibe 10 mg FDC, obicetrapib 10 mg monotherapy, ezetimibe 10 mg monotherapy, or placebo administered daily for 84 days. The co-primary endpoints in the intention-to-treat population were the percent LDL cholesterol changes in the FDC group compared with placebo, ezetimibe monotherapy, and obicetrapib monotherapy, and the placebo-adjusted change in the obicetrapib monotherapy group. The trial was prospectively registered (NCT06005597) and is completed. FINDINGS: Between March 4 and July 3, 2024, 407 participants were randomly assigned. The median age was 68·0 years (IQR 62·0-73·0) and 177 (43%) were female. Mean baseline LDL cholesterol was 2·4 mmol/L, 2·5 mmol/L, 2·6 mmol/L, and 2·5 mmol/L in the placebo (n=102), ezetimibe monotherapy (n=101), obicetrapib monotherapy (n=102), and FDC groups (n=102), respectively. At day 84, percent differences in LDL cholesterol reduction with the FDC were -48·6% (95% CI -58·3 to -38·9) versus placebo, -27·9% (-37·5 to -18·4) versus ezetimibe, and -16·8% (-26·4 to -7·1) versus obicetrapib. Obicetrapib monotherapy decreased LDL cholesterol by 31·9% (22·1 to 41·6) versus placebo. Adverse event rates were similar in the FDC (52 [51%] of 102), obicetrapib (55 [54%] of 102), and ezetimibe (54 [53%] of 101) groups and lowest with placebo (38 [37%] of 102). Serious adverse event rates were generally similar across FDC (three [3%] of 102), obicetrapib (six [6%] of 102), ezetimibe (seven [7%] of 101), and placebo (four [4%] of 102) groups. Deaths occurred in one [1%] of 102 participants with FDC, one [1%] of 102 with obicetrapib, one [1%] of 101 with ezetimibe, and none with placebo.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly used for severe aortic stenosis, but debris embolization during the procedure can lead to strokes, impacting survival and quality of life. The role of cerebral embolic protection devices (CEPDs) in mitigating stroke risk remains debated. We aim to evaluate the impact of CEPDs on the risk of stroke and neurocognitive outcomes after TAVI. METHODS: Six databases (PubMed, Scopus, Web of Science, Cochrane, Embase, and Ovid) were searched until 20 January 2023. Original randomized controlled trials (RCTs) were only included and critically appraised using the Cochrane risk of bias (ROB) tool. RESULTS: Seven RCTs (4091 patients) were analyzed. CEPDs significantly reduced the risk of disabling stroke within 2-5 days post-TAVI (relative risk = 0.455, 95% CI: [0.214, 0.967]; p = 0.041). However, there was no significant difference in disabling stroke risk between the two groups at the 30-day follow-up (relative risk = 1.295, 95% CI: [0.373, 4.493]; p = 0.684). No significant differences were observed in non-disabling or overall stroke rates at 2-5 days, 30 days, or 90 days. Additionally, CEPDs did not significantly affect risks of life-threatening bleeding, major vascular complications, mortality, or acute kidney injury. CONCLUSION: CEPDs are effective in reducing disabling stroke risk in the immediate post-TAVI period (2-5 days) but did not significantly affect the rates of non-disabling stroke, overall stroke, or disabling stroke after 30 days when compared to non-CEPD use. These findings suggest that CEPDs may offer short-term neuroprotection.

We assessed if implementation of a high-sensitivity cardiac troponin I (hs-cTnI) assay and 0/2-hour diagnostic protocol for evaluation of suspected acute coronary syndromes was associated with improved resource utilization by retrospectively studying adult emergency department (ED) encounters for chest pain/discomfort at 21 hospitals in an integrated health system. The hs-cTnI assay (Beckman Access) and corresponding 0/2-hour protocol were introduced on November 16, 2022. The preimplementation period was January 1, 2018 to June 30, 2019 (prior to the COVID-19 pandemic) and the postimplementation period was January 1, 2023 to June 30, 2024. Co-primary outcomes were ED disposition and 30-day coronary testing, assessed following adjustment for confounders and within strata of predicted risk. There were 87,647 preimplementation and 97,677 postimplementation encounters with similar demographics (median age 59 years, 55.2% vs 55.5% female) and risk factors (diabetes 26.6% vs 25.8%; chronic kidney disease 13.5% vs 13.6%; coronary revascularization 12.3% vs 10.6%). Adjusted prepost analyses revealed an increase in ED discharges (75.0% vs 78.9%, adjusted difference +3.9%, 95% CI +3.4% to +4.4%) and a decrease in 30-day coronary testing (36.2% vs 24.1%, adjusted difference-12.1%, 95% CI -12.9% to --11.4%). Notably, results differed by predicted risk strata, with decreased ED discharges and increased 30-day coronary testing among nonlow risk encounters. In conclusion, hs-cTnI assay and protocol implementation was associated with decreased overall resource utilization among ED patients with chest pain, despite increased utilization among nonlow risk encounters. Structured use of hs-cTn assays can improve alignment between risk and resource allocation in this population.