Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia.

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels (≥100 and ≤160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg, or uptitrated their atorvastatin to 40 mg; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg. Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II. At the end of period I, ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg (22.2% vs 9.5% or 13.0%, respectively, p <0.001). At the end of period II, ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg (17.4% vs 6.9%, p <0.001); switching from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg (17.1% vs 7.5%, p <0.001). Relative to comparative treatments, ezetimibe added to atorvastatin 10 mg (period I) or atorvastatin 20 mg (period II) produced significantly greater percent attainment of LDL-C targets <100 or <70 mg/dl, and significantly greater percent reductions in total cholesterol, non-high-density lipoprotein cholesterol, most lipid and lipoprotein ratios, and apolipoprotein B (except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg). Reports of adverse experiences were generally similar among groups. In conclusion, treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to (or doubling) rosuvastatin at the compared doses.

Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy.

Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score <150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested.