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This phase 3 trial evaluated the safety and efficacy of inclisiran, a small interfering RNA that inhibits hepatic PCSK9 synthesis, in 482 adults with heterozygous familial hypercholesterolemia, who received subcutaneous injections of inclisiran or placebo on days 1, 90, 270, and 450. Changes in cholesterol were assessed up to day 540.

Inclisiran, a small interfering RNA therapeutic, reduces hepatic synthesis of PCSK9. In two separate randomized trials, subcutaneous injections of inclisiran on day 1, day 90, and then every 6 months reduced LDL cholesterol levels by approximately 50% at month 17, with a modest excess of injection-site adverse events.

Inclisiran, a small interfering RNA that targets PCSK9 mRNA, was given as a single injection at baseline or in two doses at baseline and 90 days. At 180 days, LDL cholesterol was significantly lowered among persons at high cardiovascular risk who had elevated levels at baseline. Low-density lipoprotein (LDL) cholesterol is a causal factor in atherosclerotic cardiovascular disease. Statins have been shown to reduce LDL cholesterol levels and cardiovascular events in large outcome trials, findings that have made them the therapeutic cornerstone of clinical practice. 1 Despite the proven efficacy of statins, there is considerable variability in individual responses to these drugs. 2 Furthermore, some observational data suggest that as many as half of persons who begin statin therapy discontinue it within a year. 3 Moreover, among patients receiving statin therapy who are at high risk for cardiovascular disease and who have persistent elevation of LDL cholesterol levels, the . . .

Dalcetrapib, an inhibitor of cholesteryl ester transfer protein, raises HDL cholesterol levels. In this clinical trial involving patients with an acute coronary syndrome, dalcetrapib had no beneficial effect on clinical outcomes, despite raising HDL cholesterol levels. High-density lipoproteins (HDLs) participate in the process of cellular cholesterol efflux and may have additional protective effects against atherothrombosis. 1 An inverse association between levels of HDL cholesterol and incident events of coronary heart disease has been shown in observational studies 2 , 3 and persists in most post hoc analyses and meta-analyses of trials of statin therapy for patients with cardiovascular risk factors, chronic cardiovascular disease, or recent acute coronary syndrome. 4 – 10 However, it remains uncertain whether pharmacologic intervention that raises HDL cholesterol levels results in decreased cardiovascular risk. 11 – 16 Moreover, changes in HDL cholesterol levels may not reflect changes in the . . .

The US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA. We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data. CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = -0.52, p=0.002) between CCP usage per hospital admission and deaths occurring 2 weeks after admission, and this finding was robust to examination of deaths taking place 1, 2, or 3 weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021. A strong inverse correlation between CCP use and mortality per admission in the USA provides population-level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths. There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

To define the effect of a history of cancer on in-hospital and long-term mortality after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). In this retrospective cohort study of 2346 patients with STEMI enrolled in the Mayo Clinic PCI registry from November 1, 2000, through October 31, 2010, we identified 261 patients (11.1%) with a history of cancer. The in-hospital and long-term outcomes (median follow-up, 6.2 years; interquartile range=4.3-8.5 years), including cardiac and noncardiac death and heart failure hospitalization, of these patients were compared with those of 1313 cancer-negative patients matched on age, sex, family history of coronary artery disease, and date of STEMI. Patients with cancer had higher in-hospital noncardiac (1.9% vs 0.4%; P=.03) but similar cardiac (5.8% vs 4.6%; P=.37) mortality as matched controls. The group at highest acute mortality risk were those diagnosed as having cancer within 6 months before STEMI (hazard ratio [HR]=7.0; 95% CI, 1.4-34.4; P=.02). At 5 years, patients with cancer had similar cardiac mortality (4.2% vs 5.8%; HR=1.27; 95% CI, 0.77-2.10; P=.35) despite more heart failure hospitalizations (15% vs 10%; HR=1.72; 95% CI, 1.18-2.50; P=.01) but faced higher noncardiac mortality (30.0% vs 11.0%; HR=3.01; 95% CI, 2.33-3.88; P<.001) than controls, attributable solely to cancer-related deaths. One in 10 patients in this contemporary registry of patients undergoing primary PCI for STEMI has a history of cancer. These patients have more than a 3 times higher acute in-hospital and long-term noncardiac mortality risk but no increased acute or long-term cardiac mortality risk with guideline-recommended cardiac care.

The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. In this paper, we review case series that report on patients with the transient left ventricular apical ballooning syndrome to better characterize patients presenting with the syndrome. We identified 7 case series that reported on at least 5 consecutive patients with the transient left ventricular apical ballooning syndrome. The syndrome more often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years). Patients commonly present with ST-segment elevation in the precordial leads, chest pain, relatively minor elevation of cardiac enzyme and biomarker levels, and transient apical systolic left ventricular dysfunction despite the absence of obstructive epicardial coronary disease. An episode of emotional or physiologic stress frequently precedes presentation with the syndrome. The in-hospital mortality rate seems to be low, as does the risk for recurrence.

Obesity is linked to cardiovascular disease. The global increase in sedentary lifestyle is an important factor contributing to the rising prevalence of the obesity epidemic. Traditionally, counseling has focused on moderate- to vigorous-intensity exercise, with disappointing results. Nonexercise activity thermogenesis (NEAT) is an important component of daily energy expenditure. It represents the common daily activities, such as fidgeting, walking, and standing. These high-effect NEAT movements could result in up to an extra 2000 kcal of expenditure per day beyond the basal metabolic rate, depending on body weight and level of activity. Implementing NEAT during leisure-time and occupational activities could be essential to maintaining a negative energy balance. NEAT can be applied by being upright, ambulating, and redesigning workplace and leisure-time environments to promote NEAT. The benefits of NEAT include not only the extra calories expended but also the reduced occurrence of the metabolic syndrome, cardiovascular events, and all-cause mortality. We believe that to overcome the obesity epidemic and its adverse cardiovascular consequences, NEAT should be part of the current medical recommendations. The content of this review is based on a literature search of PubMed and the Google search engine between January 1, 1960, and October 1, 2014, using the search terms physical activity, obesity, energy expenditure, nonexercise activity thermogenesis, and NEAT.

Cardiac arrest is the leading cause of death in Europe and the United States. Many patients who are initially resuscitated die in the hospital, and hospital survivors often have substantial neurologic dysfunction. Most cardiac arrests are caused by coronary artery disease; patients with coronary artery disease likely benefit from early coronary angiography and intervention. After resuscitation, cardiac arrest patients remain critically ill and frequently suffer cardiogenic shock and multiorgan failure. Early cardiopulmonary stabilization is important to prevent worsening organ injury. To achieve best patient outcomes, comprehensive critical care management is needed, with primary goals of stabilizing hemodynamics and preventing progressive brain injury. Targeted temperature management is frequently recommended for comatose survivors of cardiac arrest to mitigate the neurologic injury that drives outcomes. Accurate neurologic assessment is central to managing care of cardiac arrest survivors and should combine physical examination with objective neurologic testing, with the caveat that delaying neurologic prognosis is essential to avoid premature withdrawal of supportive care. A combination of clinical findings and diagnostic results should be used to estimate the likelihood of functional recovery. This review focuses on recent advances in care and specific cardiac intensive care strategies that may improve morbidity and mortality for patients after cardiac arrest. •Coronary angiography is associated with improved outcomes after cardiac arrest.•Early cardiopulmonary stabilization may improve outcomes after cardiac arrest.•Targeted temperature management is recommended for comatose cardiac arrest patients.•Multimodality testing is needed to determine neurologic prognosis after arrest.