Tandem lesions associate with angiographic progression of coronary artery stenoses.

Background: Although the clinical factors associated with progression of coronary artery disease have been well studied, the angiographic predictors are less defined. Objectives: Our objective was to study the clinical and angiographic factors that associate with progression of coronary artery stenoses. Methods: We conducted a retrospective analysis of consecutive patients undergoing multiple, clinically indicated invasive coronary angiograms with an interval greater than 6 months, between January 2013 and December 2016. Lesion segments were analysed using Quantitative Coronary Angiography (QCA) if a stenosis ≥ 20 % was identified on either angiogram. Stenosis progression was defined as an increase ≥ 10 % in stenosis severity, with progressor groups analysed on both patient and lesion levels. Mixed-effects regression analyses were performed to evaluate factors associated with progression of individual stenoses. Results: 199 patients were included with 881 lesions analysed. 108 (54.3 %) patients and 186 (21.1 %) stenoses were classified as progressors. The median age was 65 years (IQR 56-73) and the median interval between angiograms was 2.1 years (IQR 1.2-3.0). On a patient level, age, number of lesions and presence of multivessel disease at baseline were each associated with progressor status. On a lesion level, presence of a stenosis downstream (OR 3.07, 95 % CI 2.04-4.63, p < 0.001) and circumflex artery stenosis location (OR 1.81, 95 % CI 1.21-2.7, p = 0.004) were associated with progressor status. Other lesion characteristics did not significantly impact progressor status or change in stenosis severity. Conclusion: Coronary lesions which have a downstream stenosis may be at increased risk of stenosis progression. Further research into the mechanistic basis of this finding is required, along with its implications for plaque vulnerability and clinical outcomes.

Obicetrapib on Top of Maximally Tolerated Lipid-Modifying Therapies in Participants With or at High Risk for Atherosclerotic Cardiovascular Disease: Rationale and Designs of BROADWAY and BROOKLYN.

Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events. BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a) and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024. These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.

The Role of Whole Blood Hemostatic Resuscitation in Bleeding Geriatric Trauma Patients.

INTRODUCTION: Whole blood (WB) has recently gained increased popularity as an adjunct to the resuscitation of hemorrhaging civilian trauma patients. We aimed to assess the nationwide outcomes of using WB as an adjunct to component therapy (CT) versus CT alone in resuscitating geriatric trauma patients. METHODS: We performed a 5-y (2017-2021) retrospective analysis of the Trauma Quality Improvement Program. We included geriatric (age, ≥65 y) trauma patients presenting with hemorrhagic shock (shock index >1) and requiring at least 4 units of packed red blood cells in 4 h. Patients with severe head injuries (head Abbreviated Injury Scale ≥3) and transferred patients were excluded. Patients were stratified into WB-CT versus CT only. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications. Multivariable regression analysis was performed, adjusting for potential confounding factors. RESULTS: A total of 1194 patients were identified, of which 141 (12%) received WB. The mean ± standard deviation age was 74 ± 7 y, 67.5% were male, and 83.4% had penetrating injuries. The median [interquartile range] Injury Severity Score was 19 [13-29], with no difference among study groups (P = 0.059). Overall, 6-h, 24-h, and in-hospital mortality were 16%, 23.1%, and 43.6%, respectively. On multivariable regression analysis, WB was independently associated with reduced 24-h (odds ratio, 0.62 [0.41-0.94]; P = 0.024), and in-hospital mortality (odds ratio, 0.60 [0.40-0.90]; P = 0.013), but not with major complications (odds ratio, 0.78 [0.53-1.15]; P = 0.207). CONCLUSIONS: Transfusion of WB as an adjunct to CT is associated with improved early and overall mortality in geriatric trauma patients presenting with severe hemorrhage. The findings from this study are clinically important, as this is an essential first step in prioritizing the selection of WB resuscitation for geriatric trauma patients presenting with hemorrhagic shock.

Neural cell-types and circuits linking thermoregulation and social behavior.

Understanding how social and affective behavioral states are controlled by neural circuits is a fundamental challenge in neurobiology. Despite increasing understanding of central circuits governing prosocial and agonistic interactions, how bodily autonomic processes regulate these behaviors is less resolved. Thermoregulation is vital for maintaining homeostasis, but also associated with cognitive, physical, affective, and behavioral states. Here, we posit that adjusting body temperature may be integral to the appropriate expression of social behavior and argue that understanding neural links between behavior and thermoregulation is timely. First, changes in behavioral states-including social interaction-often accompany changes in body temperature. Second, recent work has uncovered neural populations controlling both thermoregulatory and social behavioral pathways. We identify additional neural populations that, in separate studies, control social behavior and thermoregulation, and highlight their relevance to human and animal studies. Third, dysregulation of body temperature is linked to human neuropsychiatric disorders. Although body temperature is a "hidden state" in many neurobiological studies, it likely plays an underappreciated role in regulating social and affective states.

Third-party virus specific T cells for the treatment of double stranded DNA viral reactivation and PTLD after solid organ transplant.

Reactivation or primary infection with double stranded DNA viruses is common in recipients of solid organ transplants and is associated with significant morbidity and mortality. Treatment with conventional anti-viral medications is limited by toxicities, resistance, and lack of effective options for adenovirus and BKPyV. Virus-specific T-cells (VSTs) have been shown to be an effective treatment for infections with adenovirus, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Most of these studies have been conducted in stem cell recipients and no large studies have been published in the solid organ transplant population to date. In this study we report on the outcome of quadrivalent third party VST infusions in 98 recipients of solid organ transplants in the context of an open label phase 2 trial. The ninety-eight patients received a total of 181 infusions, with a median of 2 infusions per patient. The overall response rate was 45% for BKPyV, 65% for CMV, 68% for Adenovirus, and 61% for EBV. Twenty percent of patients with PTLD had a complete response and 40% a partial response. All the VST infusions were well tolerated. We conclude that VSTs are safe and effective in the treatment of viral infections in solid organ transplant recipients.

Pediatric Acute Compartment Syndrome in Long Bone Fractures: Who is at Risk?

INTRODUCTION: There is a paucity of large-scale data on the factors that suggest an impending or underlying extremity pediatric acute compartment syndrome (ACS). In addition, literature regarding the timing of operative fixation and the risk of ACS is mixed. We aimed to describe the factors associated with pediatric ACS. METHODS: Analysis of 2017-2019 Trauma Quality Improvement Program. We included patients aged <18 y diagnosed with upper extremity (UE) and lower extremity (LE) fractures. Burns and insect bites/stings were excluded. Multivariable regression analyses were performed to identify the predictors of ACS. RESULTS: 61,537 had LE fractures, of which 0.5% developed ACS. 76,216 had UE fractures, of which 0.16% developed ACS. Multivariable regression analyses identified increasing age, male gender, motorcycle collision, and pedestrian struck mechanisms of injury, comminuted and open fractures, tibial and concurrent tibial and fibular fractures, forearm fractures, and operative fixation as predictors of ACS (P value <0.05). Among LE fractures, 34% underwent open reduction internal fixation (time to operation = 14 [8-20] hours), and 2.1% underwent ExFix (time to operation = 9 [4-17] hours). Among UE fractures, 54% underwent open reduction internal fixation (time to operation = 11 [6-16] hours), and 1.9% underwent ExFix (time to operation = 9 [4-14] hours). Every hour delay in operative fixation of UE and LE fractures was associated with a 0.4% increase in the adjusted odds of ACS (P value <0.05). CONCLUSIONS: Our results may aid clinicians in recognizing children who are "at risk" for ACS. Future studies are warranted to explore the optimal timing for the operative fixation of long bone fractures to minimize the risk of pediatric ACS.

Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Healthcare and economic cost burden of emergency medical services treated non-traumatic shock using a population-based cohort in Victoria, Australia.

OBJECTIVES: We aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock. DESIGN: We conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method. The impact on productivity was assessed using a Markov state-transition model with a 3-year horizon. SETTING: Patients older than 18 years of age with shock not related to trauma who received care by EMS (1 January 2015-30 June 2019) in Victoria, Australia were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome assessed was the total healthcare expenditure. Secondary outcomes included healthcare expenditure stratified by shock aetiology, years of life lived (YLL), productivity-adjusted life-years (PALYs) and productivity losses. RESULTS: A total of 21 334 patients (mean age 65.9 (±19.1) years, and 9641 (45.2%) females were treated by EMS with non-traumatic shock with an average healthcare-related cost of $A11 031 per episode of care and total cost of $A280 million. Annual costs remained stable throughout the study period, but average costs per episode of care increased (Ptrend=0.05). Among patients who survived to hospital, the average cost per episode of care was stratified by aetiology with cardiogenic shock costing $A24 382, $A21 254 for septic shock, $A19 915 for hypovolaemic shock and $A28 057 for obstructive shock. Modelling demonstrated that over a 3-year horizon the cohort lost 24 355 YLLs and 5059 PALYs. Lost human capital due to premature mortality led to productivity-related losses of $A374 million. When extrapolated to the entire Australian population, productivity losses approached $A1.5 billion ($A326 million annually). CONCLUSION: The direct healthcare costs and indirect loss of productivity among patients with non-traumatic shock are high. Targeted public health measures that seek to reduce the incidence of shock and improve systems of care are needed to reduce the financial burden of this syndrome.

Surgical stabilization of rib fractures: The impact of volume and the need for standardized indications.

INTRODUCTION: We aimed to examine impact of trauma center (TC) surgical stabilization of rib fracture (SSRF) volume on outcomes of patients undergoing SSRF. METHODS: Blunt rib fracture patients who underwent SSRF were included from ACS-TQIP2017-2021. TCs were stratified according to tertiles of SSRF volume:low (LV), middle, and high (HV). Outcomes were time to SSRF, respiratory complications, prolonged ventilator use, mortality. RESULTS: 16,872 patients were identified (LV:5470,HV:5836). Mean age was 56 years, 74% were male, median thorax-AIS was 3. HV centers had a lower proportion of patients with flail chest (HV41% vs LV50%), pulmonary contusion (HV44% vs LV52%) and had shorter time to SSRF(HV58 vs LV76 â€‹h), less respiratory complications (HV3.2% vs LV4.5%), prolonged ventilator use (HV15% vs LV26%), mortality (HV2% vs LV2.6%) (all p â€‹< â€‹0.05). On multivariable regression analysis, HV centers were independently associated with reduced time to SSRF(ߠ​= â€‹-18.77,95%CI â€‹= â€‹-21.30to-16.25), respiratory complications (OR â€‹= â€‹0.67,95%CI â€‹= â€‹0.49-0.94), prolonged ventilator use (OR â€‹= â€‹0.49,95%CI â€‹= â€‹0.41-0.59), but not mortality. CONCLUSIONS: HV SSRF centers have improved outcomes, however, there are variations in threshold for SSRF and indications must be standardized. LEVEL OF EVIDENCE: Level III. STUDY TYPE: Therapeutic/Care Management.

Optimal Medical Therapy for Stable Ischemic Heart Disease in 2024: Focus on Blood Pressure and Lipids.

Hypertension and dyslipidemia are 2 highly prevalent and modifiable risk factors in patients with stable ischemic heart disease. Multiple lines of evidence demonstrate that lowering blood pressure and low-density lipoprotein cholesterol improves clinical outcomes in patients with ischemic heart disease. Accordingly, clinical guidelines recommend intensive treatment targets for these high-risk patients. This article summarizes the pathophysiology, supporting evidence, and treatment recommendations for management of hypertension and dyslipidemia among patients with manifest ischemic heart disease and points to future research and unmet clinical needs.

Defining the Problem: 53 Years of Firearm Violence Afflicting America's Schools.

BACKGROUND: Firearm violence and school shootings remain a significant public health problem. This study aimed to examine how publicly available data from all 50 states might improve our understanding of the situation, firearm type, and demographics surrounding school shootings. STUDY DESIGN: School shootings occurring in the US for 53 years ending in May 2022 were analyzed, using primary data files that were obtained from the Center for Homeland Defense and Security. Data analyzed included situation, injury, firearm type, and demographics of victims and shooters. We compared the ratio of fatalities per wounded after stratifying by type of weapon. Rates (among children) of school shooting victims, wounded, and fatalities per 1 million population were stratified by year and compared over time. RESULTS: A total of 2,056 school shooting incidents involving 3,083 victims were analyzed: 2,033 children, 5 to 17 years, and 1,050 adults, 18 to 74 years. Most victims (77%) and shooters (96%) were male individuals with a mean age of 18 and 19 years, respectively. Of the weapons identified, handguns, rifles, and shotguns accounted for 84%, 7%, and 4%, respectively. Rifles had a higher fatality-to-wounded ratio (0.45) compared with shooters using multiple weapons (0.41), handguns (0.35), and shotguns (0.30). Linear regression analysis identified a significant increase in the rate of school shooting victims (ß = 0.02, p = 0.0003), wounded (ß = 0.01, p = 0.026), and fatalities (ß = 0.01, p = 0.0003) among children over time. CONCLUSIONS: Despite heightened public awareness, the incidence of school shooting victims, wounded, and fatalities among children has steadily and significantly increased over the past 53 years. Understanding the epidemic represents the first step in preventing continued firearm violence in our schools.

The effectiveness of visualising plaque on cardiac computed tomography in modifying risk factors for cardiovascular disease: A systematic review.

Cardiovascular disease (CVD) is the leading cause of disease burden worldwide, with a significant proportion of cases and deaths attributable to modifiable risk factors. Recent interest has emerged in using cardiac computed tomography (CT) imaging as a tool to enhance motivation and drive positive behavioural changes. However, the impact of providing visual feedback of plaque from CT on risk factor control and individual health behaviours remains understudied. This study aimed to assess the effects of visual feedback from cardiac CT imaging on health-related behaviours and risk factor control. A systematic search of electronic databases was conducted, yielding nine studies (five randomised controlled trials and four observational studies) for analysis. The results varied, but based on the limited low-quality data, CT imaging appears to have short-term favourable effects on cholesterol levels and systolic blood pressure reductions, and positive dietary behavioural changes. Further research is warranted to better understand the long-term impact of cardiac CT imaging on health behaviours and risk factor modification.

Managing hypercholesterolaemia.

Hypercholesterolaemia is one of the most common conditions treated by clinicians in Australia. Low-density lipoprotein cholesterol (LDL-C) plays a causal role in the development and progression of atherosclerosis and cardiovascular disease. Every 1 mmol/L reduction in LDL-C concentration is associated with a 21 to 25% reduction in the relative risk of prospective atherosclerotic cardiovascular events, and emerging evidence suggests this benefit increases over time. Absolute cardiovascular risk assessment identifies patients likely to derive the most benefit from lowering LDL-C concentration, and helps determine the intensity of their treatment regimens and targets. Optimal management of LDL-C may require combination treatment with multiple classes of drugs.

Impact of Resuscitation Adjuncts on Post-Intubation Hypotension in Patients with Isolated TBI.

INTRODUCTION: Post-intubation hypotension (PIH) is a risk factor of endotracheal intubation (ETI) after injury. For those with traumatic brain injury (TBI), one episode of hypotension can potentiate that injury. This study aims to identify the resuscitation adjuncts which may decrease the incidence of PIH in this patient population. METHODS: This is a 4-year (2019-2022) prospective observational study at a level I trauma center. Adult (≥18) patients with isolated TBI requiring ETI in the trauma bay were included. Blood pressures were measured 15 minutes pre- and post-intubation. Primary outcome was PIH, defined as a decrease in SBP ≥ 20% from baseline or to<80 mmHg, or any decrease in MAP to ≤60 mmHg. Multivariable logistic regression was performed to identify the associations of pre-intubation vasopressor, hypertonic saline (HTS), PRBC, and crystalloids on PIH incidence. RESULTS: Of the 490 enrolled patients, 16% had mild (Head AIS ≤ 2), 35% moderate (Head AIS 3-4), and 49% severe (Head AIS ≥ 5) TBI. Mean age was 42 ± 22 years and 71% were male. Median ISS, head-AIS, and GCS were 26[19-38], 4[3-5], and 6[3-11], respectively. Mean SBP 15 minutes pre- and post-intubation were 118 ± 46 and 106 ± 45, respectively. Before intubation, 31% received HTS, 10% vasopressors, 20% crystalloids, and 14% at least one unit of PRBC (median, 2[1-2]U). Overall, 304 (62%) patients developed PIH. On multivariable regression analysis, pre-intubation use of vasopressors and HTS were associated with significantly decreased odds of PIH independent of TBI severity, 0.310 (0.102-0.944, p = 0.039) and 0.393 (0.219-0.70, p = 0.002) respectively. CONCLUSIONS: Nearly two-thirds of isolated TBI patients developed PIH. Pre-intubation vasopressors and HTS are associated with a decreased incidence of PIH. Such adjuncts should be considered prior to ETI in patients with suspected TBI. LEVEL OF EVIDENCE: III; Prospective Observational.

Could nudges reduce health literacy disparities in CVD prevention? An experiment using alternative messages for CVD risk assessment screening.

OBJECTIVE: To explore the effect of SMS nudge messages amongst people with varying health literacy on their intention to get a Heart Health Check. METHODS: A 3 (Initial SMS: scarcity, regret, or control nudge) x 2 (Reminder SMS: social norm or control nudge) factorial design was used in a hypothetical online experiment. 705 participants eligible for Heart Health Checks were recruited. Outcomes included intention to attend a Heart Health Check and psychological responses. RESULTS: In the control condition, people with lower health literacy had lower behavioural intentions compared to those with higher health literacy (p = .011). Scarcity and regret nudges closed this gap, resulting in similar intention levels for lower and higher health literacy. There was no interactive effect of the reminder nudge and health literacy (p = .724). CONCLUSION: Scarcity and regret nudge messages closed the health literacy gap in behavioural intentions compared to a control message, while a reminder nudge had limited additional benefit. Health literacy should be considered in behavioural intervention evaluations to ensure health equity is addressed. PRACTICE IMPLICATIONS: Results informed a national screening program using a universal precautions approach, where messages with higher engagement for lower health literacy groups were used in clinical practice.

Effect of PCC on outcomes of severe traumatic brain injury patients on preinjury anticoagulation.

INTRODUCTION: This study aims to evaluate effect of 4-factor PCC on outcomes of severe TBI patients on preinjury anticoagulants undergoing craniotomy/craniectomy. METHODS: In this analysis of 2018-2020 ACS-TQIP, patients with isolated blunt severe TBI (Head-AIS≥3, nonhead-AIS<2) using preinjury anticoagulants who underwent craniotomy/craniectomy were identified and stratified into PCC and No-PCC groups. Outcomes were time to surgery and mortality. Multivariable binary logistic and linear regression analyses were performed. RESULTS: 1598 patients were identified (PCC-107[7 %], No-PCC-1491[93 %]). Mean age was 74(11) years, 65 % were male, median head AIS was 4. Median time to PCC administration was 109 â€‹min. On univariable analysis, PCC group had shorter time to surgery (PCC-341, No-PCC-620 â€‹min, p â€‹= â€‹0.002), but higher mortality (PCC35 %, No-PCC21 %,p â€‹= â€‹0.001). On regression analysis, PCC was independently associated with shorter time to surgery (ߠ​= â€‹-1934,95 %CI â€‹= â€‹-3339to-26), but not mortality (aOR â€‹= â€‹0.70,95 %CI â€‹= â€‹0.14-3.62). CONCLUSION: PCC may be a safe adjunct for urgent reversal of coagulopathy in TBI patients using preinjury anticoagulants.

Asymptomatic coronary artery disease in ischaemic stroke survivors: A systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke and coronary artery disease share risk factors and stroke survivors experience a high rate of cardiac events. Recent work suggests a high burden of asymptomatic coronary artery disease (CAD) in ischaemic stroke survivors. Thus, we performed this systematic review and meta-analysis to A) estimate the prevalence of CAD in ischaemic stroke survivors without known CAD and B) evaluate the association between coronary atherosclerosis and future major adverse cardiovascular events (MACE) in stroke survivors. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis according to the PRISMA statement. We included studies investigating acute ischaemic stroke or transient ischaemic attack where participants underwent anatomical assessment of all coronary arteries. For objective B) we included studies that reported an association between coronary atherosclerosis and MACE. Two reviewers used the Newcastle-Ottawa Scale to assess risk of bias. We used random-effects modelling for our analyses. RESULTS: We identified 2983 studies of which 17 were included. These studies had a total of 6862 participants between 2008 and 2022. The pooled prevalence of any coronary atherosclerosis was 66.8% (95% CI 57.2%-75.1%) with substantial heterogeneity (I2 = 95.2%). The pooled prevalence of obstructive (>50%) stenosis was 29.3% with substantial heterogeneity (I2 = 91%). High-risk coronary anatomy (triple vessel disease or left main stenosis) was found in 7.0% (95% CI 4%-12%) with high heterogeneity I2 = 72%. One study examined high-risk plaques and found a prevalence of 5.9%. Five studies reported the association of coronary atherosclerosis with future MACE. The presence of obstructive CAD confers a HR of 8.0 (95% CI 1.7-37.1, p = 0.007) for future MACE. DISCUSSION AND CONCLUSIONS: Asymptomatic CAD is common in ischaemic stroke survivors. The presence and severity of asymptomatic CAD strongly associates with the risk of future MACE. Further evaluation of the benefits of routine coronary assessment in ischaemic stroke is warranted.

Impact of Bempedoic Acid on Total Cardiovascular Events: A Prespecified Analysis of the CLEAR Outcomes Randomized Clinical Trial.

Importance: The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. Objective: To determine the impact of bempedoic acid on the total incidence of MACE. Design, Setting, and Participants: Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Interventions: Patients were randomly assigned to treatment with bempedoic acid or placebo daily. Main Outcomes and Measures: The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. Results: A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Conclusion and Relevance: Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.