Effects of sibutramine on body weight and serum lipids: a double-blind, randomized, placebo-controlled study in 322 overweight and obese patients with dyslipidemia.

BACKGROUND: Cardiovascular risk factors associated with obesity, including dyslipidemia, can be improved by weight loss. The main dyslipidemia associated with obesity is elevated serum triglyceride and decreased serum high-density lipoprotein cholesterol (HDL-C) levels. METHODS: A total of 322 obese patients (body mass index > or = 27) with serum triglyceride levels > or = 250 mg/dL and < or = 1000 mg/dL and serum HDL-C levels < or = 45 mg/dL (women) and < or = 40 mg/dL (men) were placed on a step I American Heart Association diet and subsequently randomized to sibutramine 20 mg (n = 162) or placebo (n = 160) once daily for 24 weeks. RESULTS: Patients taking sibutramine had significantly greater mean weight loss than those receiving placebo (-4.9 kg vs -0.6 kg, P < or = .05). Forty-two percent of the sibutramine group lost > or = 5% of baseline weight and 12% lost > or = 10% compared with 8% and 3%, respectively, of the placebo group (P < or = .05). Mean decreases in serum triglyceride levels among 5% and 10% weight-loss responders in the sibutramine group were 33.4 mg/dL and 72.3 mg/dL, respectively, compared with an increase of 31.7 mg/dL among all patients receiving placebo (P < or = .05). Mean increases in serum HDL-C levels for 5% and 10% weight-loss responders in the sibutramine group were 4.9 mg/dL and 6.7 mg/dL, respectively, compared with an increase of 1.7 mg/dL among all patients in the placebo group (P < or = .05). Adverse events and discontinuation rates were similar in the sibutramine and placebo groups, although sibutramine-treated patients had mean increases in systolic and diastolic blood pressure of 2 to 3 mm Hg relative to placebo. CONCLUSIONS: In overweight and obese patients with high serum triglyceride levels and low serum HDL-C levels, treatment with sibutramine was associated with significant improvements in body weight and in serum triglyceride and HDL-C levels.

Long-term blood cholesterol-lowering effects of a dietary fiber supplement.

BACKGROUND: The study evaluated the blood cholesterol-lowering effects of a dietary supplement of water-soluble fibers (guar gum, pectin) and mostly non-water-soluble fibers (soy fiber, pea fiber, corn bran) in subjects with mild to moderate hypercholesterolemia (LDL cholesterol, 3.37-4.92 mmol/L). METHODS: After stabilization for 9 weeks on a National Cholesterol Education Program Step 1 Diet, subjects were randomly assigned to receive 20 g/d of the fiber supplement (n = 87) or matching placebo (n = 82) for 15 weeks and then receive the fiber supplement for 36 weeks. The efficacy analyses included the 125 subjects (58 fiber; 67 placebo) who were treatment and diet compliant. One hundred two (52 fiber; 50 placebo) completed the 15-week comparative phase. Of these subjects 85 (45 fiber; 40 placebo) elected to continue in the 36-week noncomparative extension phase. RESULTS: The mean decreases during the 15-week period for LDL cholesterol (LDL-C), total cholesterol (TC), and LDL-C/HDL-C ratio were greater (P < 0.001) in the fiber group. The mean changes from pre-treatment values in LDL-C, TC, and LDL-C/HDL-C ratio for subjects in the fiber group were -0.51 mmol/L (-12.1%), -0.53 mmol/L (-8.5%), and -0.30 (-9.4%), respectively. The corresponding changes in the placebo group were -0.05 mmol/L (-1.3%), -0.05 mmol/L (-0.8%), and 0.05 (1.5%), respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol (HDL-C), triglyceride, iron, ferritin, or vitamin A or E levels. Similar effects were seen over the subsequent 36-week noncomparative part of the study. CONCLUSIONS: The fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over the 51-week treatment period.

Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study.

BACKGROUND: Long-term maintenance of weight loss remains a therapeutic challenge in obesity treatment. OBJECTIVE: This multicenter, double-blind, placebo-controlled study was designed to test the hypothesis that orlistat, a gastrointestinal lipase inhibitor, is significantly more effective than a placebo in preventing weight regain. DESIGN: Obese subjects who lost > or = 8% of their initial body weight during a 6-mo lead-in of a prescribed hypoenergetic diet (4180-kJ/d deficit) with no adjunctive pharmacotherapy were randomly assigned to receive placebo, 30 mg orlistat, 60 mg orlistat, or 120 mg orlistat 3 times daily for 1 y in combination with a maintenance diet to help prevent weight regain. Of 1313 recruited subjects [body mass index (in kg/m2): 28-43], 729 subjects lost > or =8% of their initial body weight during the 6-mo weight-loss lead-in period and were enrolled in the double-blind phase. RESULTS: After 1 y, subjects treated with 120 mg orlistat 3 times daily regained less weight than did placebo-treated subjects (32.8 +/- 4.5% compared with 58.7 +/- 5.8% regain of lost weight; P < 0.001). Moreover, more subjects in the 120-mg orlistat group than in the placebo group regained < or = 25% of lost weight (47.5% of subjects compared with 29.9%). In addition, orlistat treatment (120 mg 3 times daily) was associated with significantly greater reductions in total and LDL-cholesterol concentrations than was placebo (P < 0.001). CONCLUSION: The use of orlistat during periods of attempted weight maintenance minimizes weight readjustment and facilitates long-term improvement in obesity-related disease risk factors.

Treatment with orlistat reduces cardiovascular risk in obese patients.

OBJECTIVE: To study the efficacy of orlistat, as an adjunct to dietary modification, in weight reduction and modification of cardiovascular risk factors in obese patients after 1 year of treatment DESIGN: A total of 3132 obese patients (body mass index 28-43 kg/m2) were evaluated in an analysis of pooled data from five randomized, double-blind, placebo-controlled trials of orlistat in conjunction with a hypocaloric diet. All studies included a 4-week, single-blind, placebo lead-in period during which patients followed a mildly hypocaloric diet, after which they were randomized to double-blind treatment with orlistat 120 mg three times a day (tid) or placebo for 1 year. RESULTS: After 1 year, orlistat 120 mg tid produced significantly more weight loss than placebo (9.2% vs 5.8%; P< 0.001). Furthermore, a greater proportion of orlistat-treated patients lost >5% or >10% of their initial body weight compared to placebo (69.6% vs 51.9%; P< 0.001 and 42.1% vs 22.7%; P< 0.001, respectively). Improvements in cardiovascular risk factors were observed during a 4-week placebo lead-in period. However, following randomization, orlistat-treated patients had significantly greater improvements than placebo-treated patients in several lipid parameters including total cholesterol, low-density lipoprotein-cholesterol, triglycerides, and apolipoprotein B. In addition, orlistat had a beneficial effect on oral glucose tolerance tests status, waist circumference and systolic and diastolic blood pressure. Orlistat was well tolerated and had a similar safety profile to placebo.

Efficacy of fluvastatin, a totally synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. FLUENT Study Group. Fluvastatin Long-Term Extension Trial.

The Fluvastatin Long-Term Extension Trial (FLUENT) was designed to assess the safety and efficacy of fluvastatin over a prolonged period of time. In this way, FLUENT represents a clinical scenario that is closer to office-based chronic treatment of hyperlipidemic patients. A total of 918 patients with severe primary hypercholesterolemia (mean baseline low density lipoprotein cholesterol [LDL-C], 227 mg/dL) were enrolled into the study and received open-label fluvastatin, 20 or 40 mg daily, depending on response. Results of the first year of treatment have been published previously and showed statistically significant changes in LDL-C (-30.7%), total cholesterol (-21.9%), and high density lipoprotein cholesterol (HDL-C; +3.5%). Of the original number of patients completing the 1-year study, 761 completed a second year of evaluation; the results are presented here. Any patient who did not achieve LDL-C levels of < or = 130 mg/dL could receive cholestyramine (usually 8 g/day) or fluvastatin up to 80 mg/day. At the end of the 2-year period there were significant changes in LDL-C with fluvastatin (20 mg/day, -25.4%; 40 mg/day, -30.6%; 80 mg/day, -33.7%; p < 0.001 vs baseline for all values). The combination of fluvastatin and cholestyramine changed LDL-C by -34.6%. Similar dose-response results were seen with reductions in total cholesterol and the LDL-C: HDL-C ratio. There were no unexpected or severe adverse events or laboratory abnormalities. In conclusion, fluvastatin offers a range of LDL-C reduction (25-34%) similar to other HMG-CoA reductase inhibitors, that conforms with guideline recommendations for over 90% of hypercholesterolemic patients.

Serum lipid and fecal bile acid changes with cereal, vegetable, and sugar-beet fiber feeding.

Thirty-four subjects consumed six controlled formula diets for 3 wk each, supplemented with 0 g added fiber, 10 and 30 g dietary fiber as wheat bran (WB), 10 and 30 g dietary fiber as mixed vegetable fiber (VF), and 30 g dietary fiber as sugar-beet fiber (SBF). Serum cholesterol changes for fiber free, 10 g WB, 30 g WB, 10 g VF, 30 g VF, and 30 g SBF (-0.13, -0.18, -0.05, -0.17, -0.24, and -0.70 mmol/L, respectively) were significant for 30 g VF and 30 g SBF. Reduction in total cholesterol with SBF was largely due to significant lowering of low-density-lipoprotein cholesterol. Total fecal bile acid concentrations were significantly higher with the fiber-free diet than with 30 g WB, VF, and SBF (P less than 0.001) and were also higher with 30 g SBF than with 30 g WB and 30 g VF (P less than 0.005). Daily fecal bile acid excretion was not different on 30 g SBF compared with 30 g WB and 30 g VF. Differences in cholesterol reduction across the diets could not be explained by differences in fecal bile acid excretion.

Capillary GC quantification of cholesterol oxidation products in plasma lipoproteins of fasted humans.

Cholesterol oxidation products have been hypothesized to be important factors in atherosclerosis, a process which can culminate in myocardial infarction. The relative importance of exogenous or in vivo sources of cholesterol oxidation products has not been determined. However, methodology used for cholesterol oxidation products analysis of foods is applicable to the determination of cholesterol oxidation products in human plasma lipoproteins. Such methodology, outlined in this report, permits numerous critical experiments to be conducted on the possible role of cholesterol oxidation products in coronary heart disease.

The hypolipidemic effect of locust bean gum food products in familial hypercholesterolemic adults and children.

Seventeen adults and 11 children, a group of 18 familial hypercholesterolemic (FHC) and 10 normal subjects, were fed products with and without locust bean gum (LBG) (8 to 30 g/day) to assess the hypolipidemic effect of LBG. Identical food products with and without LBG were consumed by two groups (A and B) of arbitrarily assigned patients using a cross-over design. Plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and triglycerides were measured at 2-wk intervals and compared to control feeding periods. In group A, FHC C decreased 10% and LDL-C 11%, normal subjects decreased C 6% and LDL-C 10% (p less than 0.001). In group B, FHC C decreased 17% and LDL-C 19%, normal subjects decreased cholesterol 11%, and LDL-C 6% (p less than 0.001). Cholesterol and LDL-C were lowered in FHC children in both groups. High-density lipoprotein/LDL ratios increased in both groups. The use of food products with LBG in children and adults is a unique approach to treating FHC. LBG food acceptance was good, and there were no significant side effects. LBG in food products appears to be an effective, safe approach to controlling hyperlipidemia.

Cardiac arrest in young, ostensibly healthy patients: clinical, hemodynamic, and electrophysiologic findings.

This study examines the clinical, hemodynamic, and electrophysiologic findings in a unique group of 11 young (aged 15 months to 29 years) survivors of a cardiac arrest. All patients were previously in good health, and cardiac arrest was the initial manifestation of cardiac disease in all. Overt clinical and hemodynamic abnormalities were not as common as previously reported, and in some instances apparent cardiac abnormalities failed to provide a link to cardiac arrest. No patient had congenital heart disease or hypertrophic cardiomyopathy. However, during multicatheter electrophysiologic study, sustained tachyarrhythmia was reproducibly initiated in 8 of 11 patients (73%). Young, ostensibly healthy patients who survive cardiac arrest form a diverse group. Diligent programmed intracardiac electrical stimulation may demonstrate life-threatening tachycardias in these patients. Treatment to prevent recurrence of cardiac arrest is difficult in this group of patients. However, the ability to initiate tachycardia in the electrophysiologic laboratory may be useful in the management of these patients.

Cholesterol excretion studies in familial hypercholesterolemic children and their normolipidemic siblings.

Twenty children ages 3 to 17 yr, eight with normal lipids and 12 with familial hypercholesterolemia were studied on a metabolic unit for 14 days to evaluate fecal bile acid and fecal neutral sterol excretion. The diet contained a moderately low cholesterol content, 180 to 200 mg/day. Stools were collected in three separate, 3-day pools. Fecal bile acids and fecal neutral sterols were measured using two stool markers and thin-layer, and gas-liquid chromatography techniques. Fecal neutral sterol and fecal bile acid excretion were the same for normal and familial hypercholesterolemic children on a mg/kg basis. Fecal neutral sterols in familial hypercholesterolemic children decreased with age, p less than 0.001; fecal bile acid excretion also appeared to decrease with age, but less significantly, p less than 0.07. Although the familial hypercholesterolemic children have significantly increased plasma and potentially elevated tissue or total body cholesterol, the excretion of fecal bile acids and fecal neutral sterols did not differ between familial hypercholesterolemic and normal children.

Myocardial injury after phenylpropanolamine ingestion.

Three patients developed clinical evidence of myocardial injury after acute ingestion of phenylpropanolamine, a sympathomimetic amine found in a large number of decongestant and appetite suppressant formulations. Increases in the serum creatine kinase and MB isoenzyme levels, ventricular arrhythmias, and electrocardiographic repolarisation abnormalities were seen. Excessive catecholamine stimulation has been shown to produce acute myocardial necrosis experimentally, and a similar mechanism may be present in these patients.