Oral bioavailability of pantoprazole suspended in sodium bicarbonate solution.
Two open-label, prospective, non-randomised, observational studies (study 1 with n = 19 194 patients, predominantly with CHD; study 2 with n = 19 484 patients, predominantly with DM). Patients received--almost all after statin pre-treatment--ezetimibe 10 mg plus simvastatin 10 mg (study 1: 15%, study 2: 16%), 20 mg (in 68% each), 40 mg (12%/10%) or 80 mg (1%/1%) as fixed dose combinations over 3 months (dosage at investigator's discretion).
The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.
A total of 150 patients with non-ST elevation myocardial infarction and unstable angina pectoris were enrolled to our prospective, randomized, single-blind study. Patients were divided into three groups by block randomization method. One group received 20 mg/day atorvastatin, one group received 10 mg/day rosuvastatin and the other group received 10 mg/day ezetimibe/simvastatin combination therapy, which was initiated within the first 24 hours of admission. Follow-up duration was 2 months . Biochemical investigations and hsCRP levels (by nephelometric method) were performed with 138 patients evaluated at baseline, 10th and 60th days of therapy. Decreases of hsCRP levels were analyzed with one-way MANOVA and repeated measures of ANOVA methods. Post-hoc Tukey HSD test was performed for finding the different group, when the difference was detected between the groups.
Safety end points included adverse events leading to drug discontinuation; adverse muscle, hepatobiliary, and neurocognitive events; and hemorrhagic stroke, heart failure, cancer, and noncardiovascular death. Efficacy events were as specified in the overall trial.
One hundred fifty-three patients (56 male) were included. At week 12, a significant reduction in serum uric acid levels was seen in all treatment groups (simvastatin/ezetimibe 10/10 mg: -3.8%, simvastatin 40 mg: -5.7%, and rosuvastatin 10 mg: -3.8%; P < .05 compared with baseline; P = not significant [NS] for comparison between groups). Fractional excretion of uric acid nonsignificantly increased in all groups (simvastatin/ezetimibe 10/10 mg: +6.8%, simvastatin 40 mg: +6.8%, and rosuvastatin 10 mg: +5.9%). The reduction in serum uric acid levels correlated with the increase in fractional excretion of uric acid and baseline uric acid levels. Renal function parameters as well as serum levels and fractional excretions of electrolytes remained unchanged in all groups. Changes in serum lipids were similar across groups.
LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (-20.8%) than by doubling the dose of simvastatin to 40 mg (-0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated.
The recently published Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE) trial seems to raise questions regarding the notion that lipid lowering is of benefit in the prevention and treatment of vascular disease. Before one can make this conclusion, a careful analysis of the trial, including the subjects included and the surrogate end point studied, is required. The results of this study should be taken in context with those of many other studies showing that lipid lowering by many approaches is beneficial. In conclusion, the public fury over this study, with physicians making unsupported statements to the press and on the Web, is unfortunate and should be discouraged in the future.
Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD).
simvastatin (20 mg), inulin from agave (7 g) and placebo of ezetimibe, or simvastatin (20 mg), ezetimibe (10 mg) and placebo of inulin from agave, daily at night, for 12 weeks.
The LDLR mutation p.W556R is a frequent and severe class II defect for FH. The affected homozygote FH patients have a total loss of the functional LDLR and-as expected-do not respond on statin therapy and require LDL apheresis. In contrast, heterozygote FH patients with the same LDLR defect respond exceedingly well to standard lipid-lowering therapy, illustrating that the knowledge of the primary LDLR defect enables us to foresee the expected drug effects.
Energy loss index decreased (0.85 cm(2)/m(2) vs. 0.77 and 0.75 cm(2)/m(2)) and the prevalence of low stress-corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV global load (all p < 0.001). The EF was low in only 2% of patients. Patients with low-flow AS had higher LV global load and more often low midwall shortening than those with normal-flow AS (9.66 +/- 2.23 mm Hg/ml.m(2.04) and 77%, vs. 6.38 +/- 2.04 mm Hg/ml.m(2.04) and 30%, respectively, p < 0.001). In logistic regression analysis, LV global load was a main predictor of low stress-corrected midwall shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p < 0.001), concomitant hypertension, and aortic regurgitation.