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Women are often not treated as aggressively as men to control levels of low-densitylipoprotein cholesterol (LDL-C), despite evidence that women and men realize comparablecardiovascular benefit from lipid-lowering therapy. Statins are the most effective drugscurrently available for treating hypercholesterolemia. Despite the impressive cholesterol-loweringcapacity of statins, however, many patients on statin therapy fail to reach establishedtarget levels of LDL-C. The cholesterol absorption inhibitor, ezetimibe, blocks the intestinalabsorption of dietary and biliary cholesterol, a mechanism of action complementary to thatof statins, which inhibit hepatic cholesterol synthesis. Ezetimibe coadministered with statinsproduces significant incremental reductions in LDL-C compared with statin monotherapy.Four randomized, double-blind, placebo-controlled, balanced-parallel group trialscompared the efficacy and safety of statin monotherapy (lovastatin or pravastatin 10, 20,or 40 mg; simvastatin or atorvastatin 10, 20, 40, or 80 mg) vs. ezetimibe 10 mg plus statin (asabove). A gender subset analysis (women,= 1065; men,= 796) on data pooled across thesefour trials was carried out to determine whether ezetimibe plus statin for the treatment of hypercholesterolemiais equally efficacious in women and men.Compared with statin monotherapy, ezetimibe plus statin demonstrated greater efficacyin reducing blood levels of LDL-C, apolipoprotein B, and triglycerides and raising highdensitylipoprotein cholesterol. The beneficial effects of ezetimibe were comparable in womenand men. The safety profile of subjects receiving ezetimibe plus statin was similar tothat of patients receiving statin monotherapy and similar between the two sexes.Ezetimibe plus statin was more effective than statin alone in improving thelipid profile of patients with hypercholesterolemia and was equally efficacious in womenand men. Ezetimibe plus statin was well tolerated and had a favorable safety profile in bothpatient subgroups. Ezetimibe coadministered with statins, a dual inhibition treatment strategythat targets both cholesterol absorption and synthesis, is an effective therapeutic optionfor women with hypercholesterolemia. [ABSTRACT FROM AUTHOR]

This study assessed the effect of ezetimibe coadministered with simvastatin on high-sensitivity C-reactive protein (hs-CRP) in patients with primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol ≥145 and ≤250 mg/dl and triglycerides ≤350 mg/dl were randomized to one of these daily treatments for 12 consecutive weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10 mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy groups. Ezetimibe plus simvastatin significantly reduced median hs-CRP levels compared with simvastatin monotherapy (−34.8% vs −18.2%, p< 0.01), and incremental reductions were observed at each simvastatin dose level. Combination therapy-induced significant changes in individual lipid parameters did not explain the observed decreases in hs-CRP. Thus, ezetimibe coadministered with simvastatin resulted in significant incremental decreases in hs-CRP, possibly consistent with an additional anti-inflammatory effect compared with simvastatin monotherapy. [Copyright &y& Elsevier]

Background: Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections. Methods: In this randomized, multicenter study involving evaluators who were unaware of treatment assignments, we compared the efficacy and safety of posaconazole with those of fluconazole or itraconazole as prophylaxis for patients with prolonged neutropenia. Patients received prophylaxis with each cycle of chemotherapy until recovery from neutropenia and complete remission, until occurrence of an invasive fungal infection, or for up to 12 weeks, whichever came first. We compared the incidence of proven or probable invasive fungal infections during treatment (the primary end point) between the posaconazole and fluconazole or itraconazole groups; death from any cause and time to death were secondary end points. Results: A total of 304 patients were randomly assigned to receive posaconazole, and 298 patients were randomly assigned to receive fluconazole (240) or itraconazole (58). Proven or probable invasive fungal infections were reported in 7 patients (2%) in the posaconazole group and 25 patients (8%) in the fluconazole or itraconazole group (absolute reduction in the posaconazole group, −6%; 95% confidence interval, –9.7 to –2.5%; P<0.001), fulfilling statistical criteria for superiority. Significantly fewer patients in the posaconazole group had invasive aspergillosis (2 [1%] vs. 20 [7%], P<0.001). Survival was significantly longer among recipients of posaconazole than among recipients of fluconazole or itraconazole (P=0.04). Serious adverse events possibly or probably related to treatment were reported by 19 patients (6%) in the posaconazole group and 6 patients (2%) in the fluconazole or itraconazole group (P=0.01). The most common treatment-related adverse events in both groups were gastrointestinal tract disturbances. Conclusions: In patients undergoing chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome, posaconazole prevented invasive fungal infections more effectively than did either fluconazole or itraconazole and improved overall survival. There were more serious adverse events possibly or probably related to treatment in the posaconazole group. (ClinicalTrials.gov number, NCT00044486.) N Engl J Med 2007;356:348-59. [ABSTRACT FROM AUTHOR]