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 .)

Pre-operative liver biopsy in cirrhotic patients with early hepatocellular carcinoma represents a safe and accurate diagnostic tool for tumour grading assessment

BACKGROUND & AIMS: Knowledge of pre-operative tumour grade is crucial in the management of hepatocellular carcinoma (HCC) because it can influence recurrence and survival after surgery. The accuracy of pre-operative needle core biopsy (NCB) in tumour grading has been assessed in only a few studies with conflicting results. Our aim was to determine the long-term safety and the overall accuracy of NCB in assessing tumour grading in subjects who had undergone liver resection for a single HCC. METHODS: Eighty-one cirrhotic patients with HCC who had undergone NCB before liver resection were selected. Only patients with a single HCC and with at least a five-year-follow-up were included. Tumour grading was scored according to a modified Edmondson-Steiner classification: well/moderately (low grade) vs poorly-differentiated (high grade). RESULTS: In the 81 patients with a solitary HCC (mean size 4.1 ± 2.3cm) tumour grade was correctly identified by NCB in 74 out of 81 (91.4%) HCCs. NCB overall sensitivity and specificity were 65% and 98.1%, respectively, with a PPV of 92% and an NPV of 91%. No major complications (in particular tumour seeding) were observed. The overall survival rates at 1, 3, and 5 years were 83%, 62%, and 44%, respectively; the recurrence rate after a 5-year-follow-up was 56.2% for low grade and 82.3% for high grade tumours (p<0.007). CONCLUSIONS: Pre-operative NCB can be performed on early (<5 cm) HCC cirrhotic patients because it provides histologically useful information for HCC management with good accuracy and a low complication rate

Non-invasive methods can predict oesophageal varices in patients with biliary atresia after a Kasai procedure.

BACKGROUND: After a Kasai procedure, 70% of patients with biliary atresia develop chronic liver disease with portal hypertension and oesophageal varices. AIMS: To investigate the role of new non-invasive parameters in predicting the presence of varices in patients with biliary atresia after a Kasai procedure and to identify the cut-off values of these parameters in predicting the presence of varices. METHODS: 31 patients with biliary atresia who had undergone a Kasai portoenterostomy were studied. Clinical, biochemical and abdominal ultrasound examination, liver stiffness measurement (LSM), LSM-spleen diameter to platelet ratio score (LSPS) and upper digestive endoscopy were performed. RESULTS: 15 (47%) patients had oesophageal varices (Group A) and 16 had no varices (Group B). Median values of LSM (kPa) and LSPS were significantly higher in Group A than in Group B (LSM: 17.0 vs. 7.5, respectively; p=0.0001; LSPS: 19.62 vs. 2.94, respectively; p=0.0001). The optimal cut-offs for predicting oesophageal varices were: LSM>10.6 kPa (sensitivity: 87%, specificity: 87.5%, PPV: 87%, NPV: 87.5%, and AUC: 0.92) and LSPS ≥9.2 (sensitivity: 91%, specificity: 92%, PPV: 91%, NPV: 92%, and AUC: 0.96). CONCLUSIONS: Non-invasive methods can predict the presence of oesophageal varices in patients with biliary atresia; the sequential use of two non-invasive methods improves accuracy