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 .)

Anatomic Variations in Pituitary Endocrinopathies: Implications for the Surgical Corridor

Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded. Results There were 30 acromegalics and 31 Cushing disease patients. When compared with controls, both acromegalics and Cushing disease patients had significantly wider piriform apertures and a longer distance from the piriform aperture to the anterior face of the sphenoid sinus (p < 0.05). Acromegalics had a significantly less acute angle (19 ± 3 degrees) from the anterior nasal spine to the sphenoid (p < 0.05). Cushing disease patients had significantly lower sphenoid sinus length and shorter nasal cavity height (p < 0.05). There were no differences in intercarotid distance or carotid canal width. Conclusions As acromegalics and Cushing disease patients have known anatomic variations, the skull base surgeon should be aware of these differences and adapt their techniques and approaches as needed

Anatomic Variations in Pituitary Endocrinopathies: Implications for the Surgical Corridor.

Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded. Results There were 30 acromegalics and 31 Cushing disease patients. When compared with controls, both acromegalics and Cushing disease patients had significantly wider piriform apertures and a longer distance from the piriform aperture to the anterior face of the sphenoid sinus (p < 0.05). Acromegalics had a significantly less acute angle (19 ± 3 degrees) from the anterior nasal spine to the sphenoid (p < 0.05). Cushing disease patients had significantly lower sphenoid sinus length and shorter nasal cavity height (p < 0.05). There were no differences in intercarotid distance or carotid canal width. Conclusions As acromegalics and Cushing disease patients have known anatomic variations, the skull base surgeon should be aware of these differences and adapt their techniques and approaches as needed