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 Safety of anacetrapib in patients with or at high risk for coronary heart  disease Cannon CP; Shah S; Dansky HM; Davidson M; Brinton EA; Gotto AM; Stepanavage M; Liu SX; Gibbons P; Ashraf TB; Zafarino J; Mitchel Y; Barter PN Engl J Med  2010[Dec]; 363 (25): 2406-15BACKGROUND: Anacetrapib is a cholesteryl ester transfer protein inhibitor that  raises high-density lipoprotein (HDL) cholesterol and reduces low-density  lipoprotein (LDL) cholesterol. METHODS: We conducted a randomized, double-blind,  placebo-controlled trial to assess the efficacy and safety profile of anacetrapib  in patients with coronary heart disease or at high risk for coronary heart  disease. Eligible patients who were taking a statin and who had an LDL  cholesterol level that was consistent with that recommended in guidelines were  assigned to receive 100 mg of anacetrapib or placebo daily for 18 months. The  primary end points were the percent change from baseline in LDL cholesterol at 24  weeks (HDL cholesterol level was a secondary end point) and the safety and  side-effect profile of anacetrapib through 76 weeks. Cardiovascular events and  deaths were prospectively adjudicated. RESULTS: A total of 1623 patients  underwent randomization. By 24 weeks, the LDL cholesterol level had been reduced  from 81 mg per deciliter (2.1 mmol per liter) to 45 mg per deciliter (1.2 mmol  per liter) in the anacetrapib group, as compared with a reduction from 82 mg per  deciliter (2.1 mmol per liter) to 77 mg per deciliter (2.0 mmol per liter) in the  placebo group (P<0.001)--a 39.8% reduction with anacetrapib beyond that seen with  placebo. In addition, the HDL cholesterol level increased from 41 mg per  deciliter (1.0 mmol per liter) to 101 mg per deciliter (2.6 mmol per liter) in  the anacetrapib group, as compared with an increase from 40 mg per deciliter (1.0  mmol per liter) to 46 mg per deciliter (1.2 mmol per liter) in the placebo group  (P<0.001)--a 138.1% increase with anacetrapib beyond that seen with placebo.  Through 76 weeks, no changes were noted in blood pressure or electrolyte or  aldosterone levels with anacetrapib as compared with placebo. Prespecified  adjudicated cardiovascular events occurred in 16 patients treated with  anacetrapib (2.0%) and 21 patients receiving placebo (2.6%) (P = 0.40). The  prespecified Bayesian analysis indicated that this event distribution provided a  predictive probability (confidence) of 94% that anacetrapib would not be  associated with a 25% increase in cardiovascular events, as seen with  torcetrapib. CONCLUSIONS: Treatment with anacetrapib had robust effects on LDL  and HDL cholesterol, had an acceptable side-effect profile, and, within the  limits of the power of this study, did not result in the adverse cardiovascular  effects observed with torcetrapib. (Funded by Merck Research Laboratories;  ClinicalTrials.gov number, NCT00685776.).|Adult[MESH]|Aged[MESH]|Anticholesteremic Agents/adverse effects/*therapeutic use[MESH]|Bayes Theorem[MESH]|Cholesterol Ester Transfer Proteins/*antagonists & inhibitors[MESH]|Cholesterol, HDL/*blood[MESH]|Cholesterol, LDL/*blood[MESH]|Combined Modality Therapy[MESH]|Coronary Disease/blood/diet therapy/*drug therapy[MESH]|Double-Blind Method[MESH]|Female[MESH]|Humans[MESH]|Male[MESH]|Middle Aged[MESH]|Oxazolidinones/adverse effects/*therapeutic use[MESH]|Risk Factors[MESH]|Young Adult[MESH]
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