Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Lung Abnormalities in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: An Analysis of Paired Computed Tomography Scans Before and After Infection.

Background: Studies on the pulmonary consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are impeded by limited access to pre-SARS-CoV-2 examinations. Methods: We invited Copenhagen General Population Study participants with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) test during the first and second coronavirus disease 2019 waves in Denmark for a repeat chest computed tomography (CT) scan. Paired CT scans were independently assessed for interstitial and noninterstitial abnormalities by 2 trained radiologists. A semiquantitative CT score (ranging from 0 to 20) was used to quantify the extent of interstitial abnormalities. Results: Of 111 SARS-CoV-2-infected individuals, 102 (91.2%) experienced symptoms and 12 (11.2%) were hospitalized. Follow-up examination was performed at median of 5.4 (interquartile range, 4.1-7.8) months after a positive SARS-CoV-2 PCR test. Of 67 individuals with paired CT scans, ground glass opacities and reticulation were present in 31 (46.3%) individuals post-SARS-CoV-2 compared to 23 (34.1%) pre-SARS-CoV-2 (mean CT score, 3.0 vs 1.3; P = .011). Results were similar for nonhospitalized individuals. We did not detect development of bronchiectasis, emphysema, or nodules. Conclusions: SARS-CoV-2 infection in predominantly nonhospitalized individuals with mild disease was associated with a small increase in only interstitial lung abnormalities.

Lung Function Decline in Relation to COVID-19 in the General Population: A Matched Cohort Study With Prepandemic Assessment of Lung Function.

BACKGROUND: To quantify the potential decline in dynamic lung volumes following coronavirus disease 2019 (COVID-19) in the general population. METHODS: A prospective matched cohort study of adult Copenhagen General Population Study (CGPS) participants with a prepandemic spirometry available. CGPS individuals with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test performed repeat spirometry, a questionnaire regarding respiratory symptoms, and diffusing capacity test for carbon monoxide. A matched uninfected CGPS control sample was used, and simple regression and linear mixed effect models were computed to study lung function decline. RESULTS: A total of 606 individuals were included; 92/107 (85.9%) with positive SARS-CoV-2 PCR test experienced coronavirus disease 2019 (COVID-19) symptoms and 12 (11.2%) were hospitalized. Spirometry was performed at median 5.6 months (interquartile range, 3.9-12.8) after positive SARS-CoV-2 PCR test. COVID-19 was associated with adjusted 7.3 mL (95% confidence interval [CI], .3-14.3) and 22.6 mL (95% CI, 13.1-32.0) steeper decline in annual forced expiratory volume in first second (FEV1) and FVC or total 113.8 and 301.3 mL lower FEV1 and FVC from baseline to follow-up. Results were robust in analyses restricted to individuals not requiring hospitalization. CONCLUSIONS: COVID-19-related declines of dynamic lung volume in the general population not requiring hospitalization were small but measurable.