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Background: Fluvastatin sodium is a new, entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that may be an effective lipid-lowering agent in patients whose hyperlipidemia does not respond to dietary therapy. We conducted a study to evaluate the effects of fluvastatin on lipoprotein levels in subjects with primary hypercholesterolemia and to compare the efficacy and safety of two fluvastatin sodium dosing regimens: 20 mg once daily vs 10 mg twice daily. Design: We conducted a double-blind, placebo-controlled, multicenter trial involving 207 patients with low-density lipoprotein cholesterol levels of 4.15 mmol/L (160 mg/dL) or higher despite dietary intervention and with triglyceride levels of 3.38 mmol/L or lower. Three parallel treatment groups received 6 weeks of treatment with 20 mg of fluvastatin sodium once daily, 10 mg of fluvastatin sodium twice daily, or a placebo. Results: Total cholesterol and low-density lipoprotein cholesterol levels were reduced from baseline by 16% and 22%, respectively, with 20 mg of fluvastatin sodium once daily (P

The Expanded Clinical Evaluation of Lovastatin study, a randomized, doubled-blind, placebo- and diet-controlled multicenter trial, evaluated the efficacy and tolerability of lovastatin over 48 weeks in 8,245 patients with moderately severe hypercholesterolemia. During year 1 of follow-up of the full cohort, lovastatin at 20 or 40 mg/day, or 20 or 40 mg twice daily, produced dose-dependent decreases in low-density lipoprotein (LDL) cholesterol (24% to 40%) and triglyceride levels (10% to 19%), and increases in high-density lipoprotein (HDL) cholesterol (6.6% to 9.5%). In all, 977 patients continued their original blinded treatment for an additional year. In year 2, the the LDL cholesterol response to lovastatin was maintained, the triglyceride reductions were somewhat less, and the increases in HDL cholesterol were moderately greater than in year 1. Successive transaminase elevations >3 times the upper limit of normal were observed in only 1 patient in year 2, yielding a cumulative 2-year incidence of from 0.1% (placebo or lovastatin 20 mg/day) to 1.9% (lovastatin 80 mg/day). Myopathy occurred in only 1 patient during year 2, and over the 2-year study was observed rarely and only at lovastatin dosages of 40 and 80 mg/day. This study indicates that lovastatin maintains its efficacy over long-term follow-up, particularly in effectively lowering LDL cholesterol, is generally well tolerated, and has a favorable safety profile. (Am J Cardiol 1994;74:667-673)

Background: Niacin and lovastatin are both effective drugs for the treatment of hypercholesterolemia and are among the drugs of first choice recommended by the adult treatment panel. To date, however, no studies have directly compared the lipoprotein-modifying effects and safety of lovastatin and niacin across their usual dosage range in patients with primary hypercholesterolemia. Methods: The efficacy and safety of lovastatin and niacin were compared in a controlled, randomized, open-label study of 26 weeks' duration that was conducted at five lipid clinics. One hundred thirty-six patients with primary hypercholesterolemia participated in the study. Entry criteria were a low-density lipoprotein (LDL) cholesterol level greater than 4.37 mmol/L (160 mg/dL) with coronary heart disease and/or more than two coronary heart disease risk factors or an LDL cholesterol level greater than 5.19 mmol/L (190 mg/dL) in patients without coronary heart disease or less than two coronary heart disease risk factors. The study consisted of a 4-week diet run-in period after which eligible patients were randomly assigned to receive treatment with either lovastatin (20 mg/d) or niacin (1.5 g/d) for 10 weeks. On the basis of the LDL cholesterol response and patient tolerance, the doses were sequentially increased to 40 and 80 mg/d of lovastatin or 3 and 4.5 g/d of niacin after 10 and 18 weeks of treatment, respectively. Results: In the two patient groups, 66% of patients treated with lovastatin and 54% of patients treated with niacin underwent full dosage titration. At all time points, lovastatin was significantly (P

Oxidative modification of low-density lipoprotein (LDL) cholesterol appears to contribute to atherogenesis. Probucol reduces LDL cholesterol oxidation susceptibility, but the consistency, dose, and time course are not well described. Twelve hyperlipidemic patients were given probucol for 4 weeks at the usual dose for cholesterol reduction (1,000 mg/day), or one half (500 mg/day) or one quarter (250 mg/day) the usual dose. Lipoprotein oxidation susceptibility of apolipoprotein B-containing lipoproteins was assessed using a rapid test in which LDL cholesterol and very-low-density lipoprotein are precipitated with dextran sulfate and magnesium ions, redissolved, incubated with copper ions for 3 hours, and tested for thiobarbituric acid-reactive substances. Results are expressed as nmoles of malonyldialdehyde (MDA) generated per mg (nmol MDA/mg) non-high-density lipoprotein cholesterol. Lipoproteins from probucol-treated patients become resistant to oxidation with a predrug value of 85 [+ or -] 19, and decreasing to 3 [+ or -] 1 nmol MDA/mg after drug administration (p

Fluvastatin is a totally synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is effective in reducing cholesterol when given in a single evening dose. Absorption and rate of bioavailability may be affected when administered with food, but the effect of mealtime dosing on efficacy and safety has not been evaluated. This multicenter, double-blind, placebo-controlled crossover study was performed in 44 patients with primary hypercholesterolemia. Patients received 20 mg of fluvastatin with the evening meal and placebo at bedtime for 6 weeks, followed by 12 weeks of placebo at mealtime and fluvastatin at bedtime (group 1). Group 2 received the opposite treatment schedule, and group 3 received placebo at mealtime and at bedtime for 12 weeks before receiving 20 mg of fluvastatin at bedtime instead of placebo for the final 6 weeks. Fluvastatin with the evening meal resulted in a marginally lower peak serum concentratiqn (p

Antihypertensive drugs may affect serum lipoprotein levels in mixed populations but data in hyperlipidemic patients are scanty. Atenolol versus coliprolol effects on serum lipoproteins were compared in 159 hyperlipoproteinemic hypertensive patients. This was a randomized, double-mind, parallel-group, positive-controlled multicenter trial with centralized lipoprotein laboratory and that constancy monitoring, Blood pressure reduction and serum lipoprotein and apoprotein levels were monitored for 3 months. Both drugs reduced systolic and diastolic blood pressures. Atenolol had greater effects than coliprolol on diastolic pressure, but effects on systolic blood pressure were not different. Patients receiving atenolol had lower serum high-density lipoprotein cholesterol levels and higher low-density lipoprotein/high-density lipoprotein cholesterol ratios, whereas patients treated with coliprolol showed no contrasting changes. These differences in lipoprotein levels between drug treatment groups were statistically significant at weeks 9 and 12. The difference between drug treatments was also significant if the values of the 9- and 12-week visits were averaged. Patients taking atenolol had statistically significantly higher serum levels of total cholesterol, triglycerides and apoprotein B at 9 weeks. These divergent directional changes were consistent throughout and statistically significantly different between drugs.

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step I Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase [is greater than] 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations ([is greater than] 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/ day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated., A report is presented from a large-scale, randomized study involving 8,245 patients with moderately high levels of blood cholesterol (between 240 and 300 milligrams per deciliter) and levels of low-density lipoprotein (LDL) cholesterol (the ''bad'' cholesterol) that were 160 milligrams per deciliter or higher. Subjects were randomly assigned to receive one of four doses of lovastatin, a drug approved for lowering cholesterol levels, or a placebo drug. This article focuses on the side effects associated with lovastatin use, with particular concern for effects on liver or muscle. An elevation of liver enzymes in the blood to three times the normal upper limit was taken as indicative of possible liver toxicity. This occurred equally often in patients who received the lower dose of lovastatin (20 milligrams per day) and in those who received the placebo drug (0.1 percent), but was more frequent in patients who took the higher doses of lovastatin (40 milligrams per day and 80 milligrams per day). Symptoms of abnormal liver function were not noted and enzyme levels returned to normal when the drug was discontinued. Elevations in the enzyme creatine kinase (CK), which could indicate muscle abnormalities, were seen in many patients, regardless of whether treatment had been with lovastatin or placebo. However, CK levels that were very high (as much as 10 times the normal upper limit) were noted in five lovastatin patients and in none of the placebo patients. The affected patients experienced symptoms such as muscle weakness, abdominal or chest pain, nausea, and fatigue, and an elevation of this magnitude is regarded as evidence of muscle damage (myopathy). Treatment was stopped for the three patients who did not have preexisting conditions associated with CK elevations and levels returned to normal within 30 days. The results of the study indicate that liver function should be monitored in patients treated with lovastatin, particularly during the first 15 months of therapy. While routine measurement of CK is of little value, clinicians who prescribe lovastatin should be aware of the possibility of muscle abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect on this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dl) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dl) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (1019%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia., A specific goal of the National Cholesterol Education Program (NCEP) is to help people achieve a blood level of low-density lipoprotein cholesterol (LDL cholesterol, the ''bad'' cholesterol) lower than 160 milligrams per deciliter in the absence of coronary artery disease (CAD) and lower than 130 milligrams per deciliter if CAD or certain CAD risk factors are present. The effectiveness of lovastatin, a drug approved for treating high LDL cholesterol levels, was evaluated in a multicenter, controlled study of 8,245 patients. The patients had moderate hypercholesterolemia (blood cholesterol levels between 240 and 300 milligrams per deciliter) and LDL cholesterol levels above 160 milligrams per deciliter. They were placed on special diets and were randomly assigned to receive one of four different dosages of lovastatin or a placebo drug for 48 weeks. Most patients without CAD or two CAD risk factors who took lovastatin met the study's LDL cholesterol goal (160 milligrams per deciliter): 81 percent of those on the lower dose of lovastatin, and 96 percent of those on the higher dose, were successful. Only 22 percent of the patients treated with the placebo were able to meet this goal. Patients with CAD or two or more CAD risk factors also benefited from lovastatin: 38 percent of those who received the lower dose met the goal, and 83 percent of those on the higher dose were successful. Only 4 percent of these patients who received the placebo lowered their LDL cholesterol levels to the level of the goal. Levels of high-density lipoprotein cholesterol (the ''good'' cholesterol) and triglycerides (another form in which fats are carried in the blood) were also affected positively by lovastatin. The results indicate that this drug is very effective in reducing the level of fats in the blood when used in combination with an appropriate diet. (Consumer Summary produced by Reliance Medical Information, Inc.)

The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study was designed to test the efficacy of lovastatin, a drug that lowers low-density-lipoprotein (LDL) cholesterol in the blood of patients with moderate hypercholesterolemia (high blood cholesterol). The study also examined dosage levels and duration of treatment for evidence of adverse effects. Researchers from 362 clinical sites took part, recording data from 8,245 patients with moderately elevated cholesterol. Four dosage levels of lovastatin and a placebo were tested for 48 weeks. Lovastatin effected changes in all lipid and lipoprotein levels, with LDL cholesterol lowered by 24 to 40 percent, according to dosage of the drug. High-density-lipoprotein (HDL) cholesterol increased by 6.6 to 9.5 percent; increased levels of HDL cholesterol appear to reduce the risk of heart disease. Triglycerides decreased by 10 to 19 percent, and the ratio of LDL-cholesterol to HDL-cholesterol also decreased. All dosage levels of lovastatin were well tolerated, causing few side effects. The most common side effect was constipation. Because these patients had only moderately elevated cholesterol levels, many were able to lower their cholesterol levels adequately through diet and use of lovastatin alone. Four out of five patients without coronary heart disease (or two or more coronary heart disease risk factors) were able to meet the guidelines of the National Cholesterol Education Program (NCEP) by taking only 20 mg of lovastatin daily, the lowest dosage level studied, and the most frequently prescribed dosage. It should be noted that at the beginning of the study, some of these lower-risk patients did not exceed the LDL cholesterol level defined by NCEP as requiring drug therapy. Higher dosages of lovastatin, and perhaps a second drug as well, may be needed for higher-risk patients to achieve recommended levels of LDL cholesterol. Patients with kidney disease, and those taking gemfibrozil or niacin (to lower cholesterol) or cyclosporine (an immunosuppressant) were excluded, therefore no adverse effects caused by kidney failure or drug interactions could be determined. It is concluded that for patients with moderately elevated cholesterol, lovastatin is highly effective and produces few side effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol ([greater than or equal to] 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The S treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume [greater than] 1 alcoholic beverage daily and 67% reporting no strenuous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy. (Am J Cardiol 1990;66:44B-55B), A large study has been designed to test the effectiveness of lovastatin in the treatment of moderate hypercholesterolemia (elevated serum cholesterol). For the purpose of this research, moderate hypercholesterolemia was defined as a fasting total cholesterol level between 240 and 300 milligrams per deciliter, low-density lipoprotein (LDL) cholesterol greater than 160 milligrams per deciliter, and triglycerides below 350 milligrams per deciliter. A total of 8,245 subjects were recruited and randomized into the double-blind, placebo-controlled study, which was conducted at 362 sites. The subjects were placed in either a placebo group or one of four treatment groups who received: a daily dose of 20 or 40 milligrams of lovastatin, or a twice-a-day dose of 20 or 40 milligrams of lovastatin. The drug treatment and low-fat diets were followed for 48 weeks. An analysis of the characteristics of the subjects in this study revealed that they were consistent with expected norms, and confirmed some of the findings of previous studies. The overall average total cholesterol level was 258 milligrams per deciliter, and the average low-density lipoprotein (LDL) cholesterol was 180 milligrams per deciliter. The average level of high-density lipoprotein (HDL) cholesterol, which is thought to exert a protective influence, was 45 milligrams per deciliter. The baseline characteristics of the recruited subjects revealed that women and blacks had higher average levels of HDL cholesterol, and that obese subjects had lower HDL cholesterol. Cigarette smoking had an adverse effect upon HDL cholesterol levels. As has been found in previous studies, both exercise and alcohol consumption had a beneficial effect on HDL cholesterol. The evaluation of the subjects revealed little variation in HDL cholesterol with age. The research design employed should enable researchers to document the long-term effects of lovastatin therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)