Daily Cardiology Research Analysis

BACKGROUND: People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack. METHODS: ARTESiA is a double-blind, double-dummy, randomised controlled trial conducted at 247 sites in 16 countries across Europe and North America. Adults aged 55 years or older with device-detected subclinical atrial fibrillation lasting from 6 min to 24 h and a CHA FINDINGS: Between May 7, 2015, and July 30, 2021, 4012 people with subclinical atrial fibrillation were randomly allocated either apixaban (n=2015) or aspirin (n=1997). A history of stroke or transient ischaemic attack was present in 346 (8·6%) participants (172 assigned to apixaban and 174 to aspirin), among whom the annual rate of stroke or systemic embolism was 1·20% (n=7; 95% CI 0·48 to 2·48) with apixaban versus 3·14% (n=18; 1·86 to 4·96) with aspirin; (hazard ratio [HR] 0·40, 95% CI 0·17 to 0·95). In participants without a history of stroke or transient ischaemic attack (n=3666; 1843 assigned to apixaban and 1823 to aspirin), the annual rate of stroke or systemic embolism was 0·74% (n=48; 95% CI 0·55 to 0·98) with apixaban versus 1·07% (n=68; 95% CI 0·83 to 1·36) with aspirin (HR 0·69, 95% CI 0·48 to 1·00). The absolute risk difference in incidence of stroke or systemic embolism at 3·5 years of follow-up was 7% (95% CI 2 to 12) in participants with versus 1% (0 to 3) in participants without a history of stroke or transient ischaemic attack. The annual rate of major bleeding in participants with a history of stroke or transient ischaemic attack was 2·26% with apixaban (n=13; 95% CI 1·21 to 3·87) versus 1·16% with aspirin (n=7; 0·47 to 2·39; HR 1·94, 95% CI 0·77 to 4·87). The absolute risk difference in major bleeding events at 3·5 years was 3% (-1 to 8) in individuals with a versus 1% (-1 to 2) in those without a history of stroke or transient ischaemic attack. INTERPRETATION: Treatment with the direct-acting oral anticoagulant apixaban in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack led to a 7% absolute risk reduction in stroke or systemic embolism over 3·5 years, compared with a 1% absolute risk reduction for individuals without a previous history of stroke or transient ischaemic attack. The corresponding absolute increase in major bleeding was 3% and 1%, respectively. Apixaban could be considered for secondary stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack. FUNDING: The Canadian Institutes of Health Research, Bristol-Myers Squibb-Pfizer Alliance, Heart and Stroke Foundation of Canada, Canadian Stroke Prevention and Intervention Network, Hamilton Health Sciences, Accelerating Clinical Trials Network, Population Health Research Institute, and Medtronic.

BACKGROUND: The Scottish Computed Tomography of the Heart (SCOT-HEART) trial demonstrated that management guided by coronary CT angiography (CCTA) improved the diagnosis, management, and outcome of patients with stable chest pain. We aimed to assess whether CCTA-guided care results in sustained long-term improvements in management and outcomes. METHODS: SCOT-HEART was an open-label, multicentre, parallel group trial for which patients were recruited from 12 outpatient cardiology chest pain clinics across Scotland. Eligible patients were aged 18-75 years with symptoms of suspected stable angina due to coronary heart disease. Patients were randomly assigned (1:1) to standard of care plus CCTA or standard of care alone. In this prespecified 10-year analysis, prescribing data, coronary procedural interventions, and clinical outcomes were obtained through record linkage from national registries. The primary outcome was coronary heart disease death or non-fatal myocardial infarction on an intention-to-treat basis. This trial is registered at ClinicalTrials.gov (NCT01149590) and is complete. FINDINGS: Between Nov 18, 2010, and Sept 24, 2014, 4146 patients were recruited (mean age 57 years [SD 10], 2325 [56·1%] male, 1821 [43·9%] female), with 2073 randomly assigned to standard care and CCTA and 2073 to standard care alone. After a median of 10·0 years (IQR 9·3-11·0), coronary heart disease death or non-fatal myocardial infarction was less frequent in the CCTA group compared with the standard care group (137 [6·6%] vs 171 [8·2%]; hazard ratio [HR] 0·79 [95% CI 0·63-0·99], p=0·044). Rates of all-cause, cardiovascular, and coronary heart disease death, and non-fatal stroke, were similar between the groups (p>0·05 for all), but non-fatal myocardial infarctions (90 [4·3%] vs 124 [6·0%]; HR 0·72 [0·55-0·94], p=0·017) and major adverse cardiovascular events (172 [8·3%] vs 214 [10·3%]; HR 0·80 [0·65-0·97], p=0·026) were less frequent in the CCTA group. Rates of coronary revascularisation procedures were similar (315 [15·2%] vs 318 [15·3%]; HR 1·00 [0·86-1·17], p=0·99) but preventive therapy prescribing remained more frequent in the CCTA group (831 [55·9%] of 1486 vs 728 [49·0%] of 1485 patients with available data; odds ratio 1·17 [95% CI 1·01-1·36], p=0·034). INTERPRETATION: After 10 years, CCTA-guided management of patients with stable chest pain was associated with a sustained reduction in coronary heart disease death or non-fatal myocardial infarction. Identification of coronary atherosclerosis by CCTA improves long-term cardiovascular disease prevention in patients with stable chest pain. FUNDING: The Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Edinburgh and Lothian's Health Foundation Trust, British Heart Foundation, and Heart Diseases Research Fund.

Metabolic rewiring underlies effective macrophages defense to respond disease microenvironment. However, the underlying mechanisms driving metabolic rewiring to enhance macrophage effector functions remain unclear. Here, we demonstrated that the metabolic reprogramming in inflammatory macrophages depended on the acetylation of CLYBL, a citramalyl-CoA lyase, at lysine 154 (K154), and blocking CLYBL-K154 acetylation restricted the release of pro-inflammatory factors. Mechanistically, we found a crucial AMPK-CLYBL acetylation positive feedback loop, triggered by toll-like receptors (TLRs), involving AMPK hypophosphorylation and CLYBL hyperacetylation. The deacetylase enzyme SIRT2 acted as the bridge between AMPK phosphorylation and CLYBL acetylation, thereby regulating macrophage polarization and the release of pro-inflammatory cytokines. Furthermore, CLYBL hypoacetylation decreased monocyte infiltration, thereby alleviating cardiac remodeling. These findings suggest that the AMPK-CLYBL acetylation positive feedback loop serves as a metabolic switch driving inflammatory response and inhibiting CLYBL-K154 acetylation may offer a promising therapeutic strategy for inflammatory response-related disorders.