Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Coronary artery disease (CAD) with associated myocardial infarction (MI) is the most common cause of morbidity and mortality in the United States.¹ Often MI is the first symptom of CAD, suggesting the need for more effective screening of high-risk, asymptomatic patients.^1,2

Background: Air pollution is associated with greater cardiovascular event risk, but the types of events and specific persons at risk remain unknown. This analysis evaluates effects of short‐term exposure to fine particulate matter air pollution with risk of acute coronary syndrome events, including ST ‐segment elevation myocardial infarction, non– ST ‐segment elevation myocardial infarction, unstable angina, and non– ST ‐segment elevation acute coronary syndrome. Methods and Results: Acute coronary syndrome events treated at Intermountain Healthcare hospitals in urban areas of Utah's Wasatch Front were collected between September 1993 and May 2014 (N=16 314). A time‐stratified case‐crossover design was performed matching fine particulate matter air pollution exposure at the time of each event with referent periods when the event did not occur. Patients served as their own controls, and odds ratios were estimated using nonthreshold and threshold conditional logistic regression models. In patients with angiographic coronary artery disease, odds ratios for a 10‐μg/m ³ increase in concurrent‐day fine particulate matter air pollution >25 μg/m³ were 1.06 (95% CI 1.02–1.11) for all acute coronary syndrome, 1.15 (95% CI 1.03–1.29) for ST ‐segment elevation myocardial infarction, 1.02 (95% CI 0.97–1.08) for non– ST ‐segment elevation myocardial infarction, 1.09 (95% CI 1.02–1.17) for unstable angina, and 1.05 (95% CI 1.00–1.10) for non– ST ‐segment elevation acute coronary syndrome events. Excess risk from fine particulate matter air pollution exposure was not observed in patients without angiographic coronary artery disease. Conclusions: Elevated fine particulate matter air pollution exposures contribute to triggering acute coronary events, especially ST ‐segment elevation myocardial infarction, in those with existing seriously diseased coronary arteries but not in those with nondiseased coronary arteries.

Medication adherence is generally low and challenging to address because patient actions control healthcare delivery outside of medical environments. Behavioral nudging changes clinician behavior, but nudging patient decision-making requires further testing. This trial evaluated whether behavioral nudges can increase statin adherence, measured as the proportion of days covered (PDC). In a 12-month parallel-group, unblinded, randomized controlled trial, adult patients in Intermountain Healthcare cardiology clinics were enrolled. Inclusion required an indication for statins and membership in SelectHealth insurance. Subjects were randomized 1:1 to control or nudges. Nudge content, timing, frequency, and delivery route were personalized by CareCentra using machine learning of subject motivations and abilities from psychographic assessment, demographics, social determinants, and the Intermountain Mortality Risk Score. PDC calculation used SelectHealth claims data. Among 182 subjects, age averaged 63.2±8.5 years, 25.8% were female, baseline LDL-C was 82.5±32.7 mg/dL, and 93.4% had coronary disease. Characteristics were balanced between nudge (n = 89) and control arms (n = 93). The statin PDC was greater at 12 months in the nudge group (PDC: 0.742±0.318) compared to controls (PDC: 0.639±0.358, P = 0.042). Adherent subjects (PDC ≥80%) were more concentrated in the nudge group (66.3% vs controls: 50.5%, P = 0.036) while a composite of death, myocardial infarction, stroke, and revascularization was non-significant (nudges: 6.7% vs control: 10.8%, P = 0.44). Persuasive behavioral nudges driven by artificial intelligence resulted in a clinically important increase in statin adherence in general cardiology patients. This precision patient decision support utilized computerized nudge design and delivery with minimal on-going human input.