Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial.

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 < .01) more effective than niacin in reducing LDL cholesterol levels (26% vs 5% at week 10, 28% vs 16% at week 18, and 32% vs 23% at week 26), whereas niacin was more effective (P < .01) in increasing high-density lipoprotein cholesterol levels (6% vs 20% at week 10, 8% vs 29% at week 18, and 7% vs 33% at week 26). Niacin reduced Lp(a) lipoprotein levels by 35% at week 26, whereas lovastatin had no effect. Cutaneous flushing was the most common side effect during treatment with niacin. CONCLUSIONS: Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins. Lovastatin was more effective in reducing LDL cholesterol concentrations, whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a) lipoprotein level. Lovastatin was better tolerated than niacin, in large part because of the common cutaneous side effects of niacin.

Antiarrhythmic effects of intravenous timolol in supraventricular arrhythmias.

The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias. In our double-blind, randomized, parallel, multiclinic study, subjects received timolol, 1 mg iv, or matching placebo as a starting dose, followed by a second and third dose of 1 mg each (or matching placebo) at 20-min intervals if the arrhythmia did not convert to sinus rhythm. Subjects in whom the sinus rhythm returned or the ventricular rate decreased to less than 100 bpm were transferred to a dosing regimen of timolol in 10-mg tablets twice a day by mouth, 1 hr after the last intravenous dose. Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo. The overall proportion of responders (either conversion to sinus rhythm or a decrease in ventricular rate to less than 100 bpm) was 68% after timolol and 7% after placebo. The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia (26 of 32 subjects and two of 38 subjects), atrial fibrillation (17 of 29 subjects and three of 32 subjects), and atrial flutter (seven of 11 subjects and one of nine subjects). The most common adverse effects were bradycardia and hypotension.

Effects of lovastatin in diabetic patients treated with chlorpropamide.

Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted.

The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.

The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study. Each active treatment period was 6 weeks in duration with intervening 2 week washout periods. Median reductions from baseline in LDL cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups, respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%. High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group. One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80 mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper limit of normal. No new or unexpected adverse effects were observed. We conclude that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with a low short-term incidence of adverse effects; our results support the continued investigation of simvastatin at these doses.

Informed consent -- why are its goals imperfectly realized?

We explored reasons for the failure of patients to recall major portions of the information on consent forms and in oral explanations about consent. Within one day of signing consent forms for chemotherapy, radiation therapy, or surgery, 200 cancer patients completed a test of their recall of the material in the consent explanation and filled out a questionnaire regarding their opinions of its purpose, content, and implications. Only 60 per cent understood the purpose and nature of the procedure, and only 55 per cent correctly listed even one major risk or complication. We found that three factors were related to inadequate recall: education, medical status, and the care with which patients thought they had read their consent forms before signing. Only 40 per cent of the patients had read the form "carefully." Most believed that consent forms were meant to "protect the physician's rights." Although most thought that consent forms were necessary and comprehensible and that they contained worthwhile information, the legalistic connotations of the forms appeared to lead to cursory reading and inadequate recall.

Information and participation preferences among cancer patients.

The present study explored the degree to which patients prefer to become informed about and to participate in their medical care. A total of 256 cancer patients completed an Information Styles Questionnaire and the Beck Hopelessness Scale. Patients' behavior and beliefs were found to incorporate the contemporary standard of informed and active involvement. Significant age trends were found: The younger the patients, the more closely they conformed to the well-informed participant standard of patient behavior; the older the patients, the more likely they were to prefer the older, nonparticipatory patient role. Patients who wanted to be involved in treatment decisions were significantly more hopeful than others. Most patients in each age group displayed high levels of hope, preferences for open communication about their illness, and a desire for maximum amounts of information.

Effects of lovastatin on natural killer cell function and other immunological parameters in man.

Suppression of cholesterol synthesis by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, such as lovastatin, has been shown to inhibit mitogen stimulated proliferation of natural killer (NK) cells and other lymphocytes in vitro. This effect is only partially overcome by provision of exogenous free or lipoprotein cholesterol but is reversed by mevalonate, suggesting that proliferating lymphocytes have a specific requirement for a nonsterol isoprenoid product of mevalonate. The effect of lovastatin (20 mg bid) on a range of immune function parameters was determined in a randomized, placebo-controlled, double-blind ex vivo study in 52 patients with primary hypercholesterolemia. No significant differences (P < 0.05) were found between lovastatin and placebo groups for basal NK or interleukin-2 (IL-2)-induced cell-mediated cytotoxicity, PHA-stimulated lymphocyte proliferation, or relative numbers of T lymphocytes (CD3+), B lymphocytes (CD19+), total NK cells (CD3-, CD16+, CD56+) and CD57+ NK cells or in immunoglobulin levels after 4 or 8 weeks of treatment. In contrast to previous in vitro data, no statistically or clinically significant changes were observed in any parameter of lymphocyte function in patients treated with lovastatin.