Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Interobserver agreement in automated metabolic tumor volume measurements of Deauville score 4 and 5 lesions at interim 18F-FDG PET in DLBCL

Introduction: Metabolic tumor volume (MTV) on interim-PET (I-PET) is a potential prognostic biomarker for diffuse large B-cell lymphoma (DLBCL). Implementation of MTV on I-PET requires consensus which semi-automated segmentation method delineates lesions most successfully with least user interaction. Methods used for baseline PET are not necessarily optimal for I-PET due to lower lesional standardized uptake values (SUV) at I-PET. Therefore, we aimed to evaluate which method provides the best delineation quality of Deauville-score (DS) 4-5 DLBCL lesions on I-PET at best interobserver agreement on delineation quality and, secondly, to assess the effect of lesional SUVmax on delineation quality and performance agreements. Methods: DS4-5 lesions from 45 I-PET scans were delineated using six semi-automated methods i) SUV 2.5, ii) SUV 4.0, iii) adaptive threshold [A50%peak], iv) 41% of maximum SUV [41%max], v) majority vote including voxels detected by ≥2 methods [MV2] and vi) detected by ≥3 methods [MV3]. Delineation quality per MTV was rated by three independent observers as acceptable or non-acceptable. For each method, observer scores on delineation quality, specific agreements and MTV were assessed for all lesions, and per category of lesional SUVmax (10). Results: In 60 DS4-5 lesions on I-PET, MV3 performed best, with acceptable delineation in 90% of lesions, with a positive agreement (PA) of 93%. Delineation quality scores and agreements per method strongly depended on lesional SUV: the best delineation quality scores were obtained using MV3 in lesions with SUVmax10, were comparable after excluding visually failed MV3 contouring. For lesions with SUVmax<10, MTVs using different methods correlated poorly. Conclusion: On I-PET, MV3 performed best and provided the highest interobserver agreement regarding acceptable delineations of DS4-5 DLBCL lesions. However, delineation method preference strongly depended on lesional SUV. Therefore, we suggest to explore an approach that identifies the optimal delineation method per lesion as function of tumor FDG uptake characteristics, i.e. SUVmax