Cardiovascular outcomes and their relationships to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial.

OBJECTIVES: In Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL), we compared cardiovascular outcomes in patients with and without chronic kidney disease (CKD) (estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2)) and analysed relationships between lipoprotein components (LC) and major coronary events (MCE) and other cardiovascular (CV) events. DESIGN: Exploratory analysis of CV endpoints in a randomized trial comparing high dose of atorvastatin to usual dose of simvastatin on MCE. SETTINGS: Patients with CKD were compared with the non-CKD patients. Cox regression models were used to study the relationships between on-treatment levels of LC and incident MCE. FINDINGS: Chronic kidney disease was strongly associated with cardiovascular end-points including total mortality. In patients with CKD, a significant benefit of high dose atorvastatin treatment was found for any CV events, stroke and peripheral artery disease, but not for MCE. However, all cardiovascular end-points except stroke and CV mortality were reduced in the non-CKD group. Differential changes in LC or relationships to LC could not explain the different treatment outcomes in MCE in the two groups. INTERPRETATION: Chronic kidney disease was a powerful risk factor for all cardiovascular end-points. The reason why the significant reductions achieved by high-dose statin treatment in most CV end-points in the non-CKD group were only in part matched by similar reductions in the CKD patients is not apparent. This difference did not result from differential changes in or relations to LC, but limited power may have increased the possibility of chance findings.

Health-related lifestyles and risk behaviours among students living in Alexandria University Hostels.

We assessed health-related lifestyles and their determinants among 600 Alexandria University students living in university hostels. Data were collected by questionnaires, and anthropometric and blood pressure measurements were taken. Most students were not satisfied with their situation in terms of accommodation, health and support. About 86% ate unhealthy diets, 33.8% were physically inactive, 25.3% were overweight or at risk of becoming overweight, 17.5% of male students were current smokers and 32.2% had poor sleep behaviours. About 28% of the students adopted 3 or more risk behaviours. About 23% reported low perceived health status and 80.3% felt they had low to moderate social support. There were significant sex differences regarding some behaviours.

Health-related lifestyles and risk behaviours among students living in Alexandria University hostels

We assessed health - related lifestyles and their determinants among 600 Alexandria students living in university hostels. Data were collected by questionnaires, and anthropometric University and blood pressure measurements were taken. Most students were not satisfied with their situation in terms of accommodation, health and support. About 86% ate unhealthy diets, 33.8% were physically inactive, 25.3% were overweight or at risk of becoming overweight, 17.5% of male students were smokers and 32.2% had poor sleep behaviours. About 28% of the students adopted 3 or more current risk behaviours. About 23% reported low perceived health status and 80.3% felt they had low to moderate social support. There were significant sex differences regarding some behaviours

Sex differences in clinical presentation and response in panic disorder: pooled data from sertraline treatment studies.

OBJECTIVE: Gender differences in clinical presentation and response to sertraline treatment were examined for patients diagnosed with DSM-III-R panic disorder with or without agoraphobia. METHOD: Data was pooled from 4 double-blind, placebo-controlled outpatient studies (males, N = 335; females, N = 338). Two were 12-week fixed-dose studies (sertraline 50 mg vs. 100 mg vs. 200 mg) and 2 were 10-week flexible-dose studies (sertraline 50-200 mg). Primary outcome measures consisted of the Clinical Global Impression-Improvement scale (CGI-I) and change in panic attack frequency. RESULTS: The clinical presentation of panic disorder was similar except that men reported an earlier age of onset, shorter duration of illness, and significantly more frequent history of alcohol and/or substance dependence/abuse. Sertraline was significantly more effective than placebo in both women and men on the 2 primary outcome measures. When between-sex efficacy was compared, women achieved significantly greater improvement than men on panic frequency and CGI-I, but had equivalent improvement on all other measures. There was no significant between-sex difference in study completion rates, or in adverse event profiles. CONCLUSIONS: There was a modest but consistent trend for women to show superior efficacy at the end of acute sertraline treatment. This gender effect only occasionally achieved significance, and must be confirmed by future treatment research.

The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies.

Data from two fixed-dose studies of sertraline in panic disorder were pooled in order to provide sufficient power for the analysis of treatment response in clinically relevant subgroups. Male and non-fertile female patients meeting DSM-III-R criteria for moderate-to-severe panic disorder with or without agoraphobia completed a 1-2 week placebo run-in period, and then were randomized to 12 weeks of double-blind treatment with either placebo, or one of three fixed daily doses of sertraline (50 mg, 100 mg, or 200 mg). Eighty-two patients were treated with placebo and 240 patients were treated with one of three doses of sertraline. All three sertraline doses produced significant efficacy compared to placebo, with no consistent evidence of a dose-response effect. For the subset of patients with subsyndromic depression at baseline [baseline Hamilton Depression Rating scale (HAM-D > 12 and < or = 21], sertraline yielded a significantly higher panic-free rate than did placebo (P = 0.021), again, by a conservative endpoint (Last Observation Carried Forward method, LOCF) analysis. Sertraline was well-tolerated at all dose levels, with no significant between-dose differences in patients discontinuing due to adverse events. The presence of mild-to-moderate subsyndromic levels of depression did not reduce the anti-panic efficacy of sertraline.

Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I.

This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (reductase inhibitor) to an accepted drug of this class in patients with moderate hypercholesterolemia. Participants remained on a cholesterol-lowering diet throughout the study. One thousand forty-nine patients were randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo. At 16 weeks the placebo group was randomized to either atorvastatin or lovastatin treatment. At 22 weeks, patients who had not met low-density lipoprotein (LDL) cholesterol target levels doubled the dose of reductase inhibitor. Efficacy evaluation was mean percent change from baseline in LDL cholesterol, triglycerides, total cholesterol, high-density-lipoprotein cholesterol, and apolipoprotein B (apoB). Safety profiles as determined by change from baseline in laboratory evaluations, ophthalmologic parameters, and reporting of adverse events were similar for the 2 reductase inhibitors. After 52 weeks, the atorvastatin group maintained a significantly greater reduction in LDL cholesterol (-37% vs -29%), triglyceride (-16% vs -8%), total cholesterol (-27% vs -21%), and apoB (-30% vs -22%) (p <0.05). More patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients (78% vs 63%, respectively), particularly those with coronary heart disease (37% vs 11%, respectively). Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events.

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials.

Preclinical and clinical data on atorvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, indicate that it has superior activity in treating a variety of dyslipidemic disorders characterized by elevations in low-density lipoprotein cholesterol (LDL-C) and/or triglycerides. Results for patients randomized in early efficacy and safety studies were combined in one database and analyzed. This analysis included a total of 231 atorvastatin-treated patients (131 with hypercholesterolemia (HC), 63 with combined hyperlipidemia (CH), 36 with hypertriglyceridemia (HTG), and 1 with hyperchylomicronemia (Fredrickson Type V)). Patients were treated with a cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step 1 diet or a more rigorous diet) and either 2.5, 5, 10, 20, 40, or 80 mg/day of atorvastatin or placebo. Efficacy was based on percent change from baseline in total cholesterol, total triglycerides, LDL-C, very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apo B), and non-HDL-C/HDL-C. Safety was assessed in all randomized patients. Atorvastatin seemed to preferentially lower those lipid and lipoprotein component(s) most elevated within each dyslipidemic state: LDL-C in patients with HC, triglycerides and VLDL-C in patients with HTG, or all 3 in patients with CH. Atorvastatin was well-tolerated with a safety profile similar to other drugs in its class.

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia.

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained > or = 3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P < 0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of < 3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P < 0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.

Atorvastatin, a New HMG-CoA Reductase Inhibitor, Does Not Affect Glucocorticoid Hormones in Patients With Hypercholesterolemia.

BACKGROUND: Atorvastatin calcium (Lipitor) is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The present study was conducted to examine the effect of pronounced cholesterol lowering on adrenal function in patients with severe hypercholesterolemia. METHODS AND RESULTS: Adrenal function was examined under basal conditions and following adrenal corticotropin hormone stimulation in 40 patients (36 with heterogeneous familial and 4 with polygenic hypercholesterolemia). The study was part of a larger study comparing the efficacy and safety of atorvastatin, colestipol, atorvastatin + colestipol, and simvastatin + colestipol treatment over a 1-year period. Maximum doses of all agents were studied: 80 mg atorvastatin once daily, 40 mg simvastatin once daily, and 20 g/day colestipol. At the end of the 1-year treatment period, reductions in low-density lipoprotein cholesterol were 57%, 54%, and 49% for the atorvastatin, colestipol + atorvastatin, and colestipol + simvastatin groups, respectively. No clinically significant changes in basal serum cortisol levels were seen in any treatment group during the 1-year treatment period. Mean serum cortisol concentrations and area under the curve for cortisol concentration versus time data following adrenal corticotropin hormone stimulation were not clinically different during treatment compared with values obtained at baseline for any of the treatment groups. CONCLUSIONS: Treatment with maximum doses of atorvastatin for 1-year did not have any adverse effects on adrenal function under basal conditions or during maximum stimulation. Similarly, colestipol therapy alone and in combination with either atorvastatin or simvastatin did not appear to affect adrenal function.