Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.

BACKGROUND: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. AIMS: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. METHODS: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. SUMMARY: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. CLINICAL TRIAL REGISTRATION: NCT03067844.

High heritability of adolescent sleep-wake behavior on free, but not school days: a long-term twin study.

Adolescence development is characterized by significant changes in sleep biology. Despite an overall decline in sleep duration and a delay in bedtime, significant interindividual variation in sleep has been reported. The aim of the current study was to examine genetic and environmental influences on sleep in adolescence using long-term (6 month) actigraphy measurements, differentiating between school and free days. Sixteen monozygotic (n = 32) and 10 dizygotic (n = 20) twin pairs (mean age 12.8 ± 1.0 years; 25 females) participated in the study. Structural equation modeling was used to compute genetic, shared environmental and unique environmental contributors to sleep behavior. We found significantly more genetic influence on sleep timing (sleep midpoint; school: 14%, free: 90%) and duration (school: 15%; free: 68%) on free compared with school days. On the other hand, the genetic influence on measures of sleep quality (sleep efficiency and sleep onset latency) was high (>60%) and less dependent on the day of measurement. Only wake after sleep onset (WASO) exhibited a strong shared environmental influence (> 52%) on both school and free days, suggesting that behavioral/environmental interventions may help reduce WASO. In addition, self-reported chronotype was also highly genetically influenced (75%). Disrupted, ill-timed, and insufficient sleep in adolescence is associated with poor mental and physical health outcomes. Our findings of a strong genetic contribution to sleep in adolescence suggest that sleep may mark a genetic vulnerability to poor outcomes.