Use Of HMG-CoA Reductase Inhibitors Research Articles

The Efficacy of Lovastatin in Lowering Cholesterol in African Americans with Primary Hypercholesterolemia

PURPOSE: To evaluate the efficacy of lovastatin in African Americans (AA) diagnosed with primary hypercholesterolemia.PATIENTS AND METHODS: Forty-seven AA patients from the King/Drew Medical Center in Los Angeles were recruited from the Hypertension, Family Practice, and General Medicine Clinics for a double-blinded, placebo-controlled trial. Forty-one patients completed the 10 week study. Eligibility for entrance into the study was determined by patient lipid profiles meeting the criteria for pharmacological intervention outlined by the National Cholesterol Education Program II guidelines. Patients were randomized into 2 groups: lovastatin 20 mg per day, or placebo. A registered dietitian counseled both groups on two visits during the study to ensure compliance with a low fat, low cholesterol diet. Lipid levels were compared at the first and last visit of the study.RESULTS: The lovastatin-treated group demonstrated significant reductions in mean total cholesterol (TC) (14.7%, 95% confidence interval [CI] −6.6 to −22.8, P <0.01) and low-density lipoprotein (LDL) cholesterol (20.0%, 95% CI −7.9 to −32.1, P <0.01) from baseline. Plasma triglyceride (TG) levels decreased by 10.5% (95% CI −2.4 to −18.6) and total cholesterol/high density lipoprotein (HDL) ratio fell below five in the lovastatin group, but neither reduction reached statistical significance. Placebo administration was not associated with any significant changes in TC, LDL, or TG. There were no significant differences between baseline and post-treatment hepatic transaminase levels in either group.CONCLUSIONS: The HMG-CoA (3-hydroxyl-3 methylglutary coenzyme A) reductase inhibitor lovastatin in a dose of 20 mg per day was effective in decreasing TC, LDL, and TG levels in an AA population. Considering that the AA population is at substantially increased risk for hypertension and cardiovascular morbidity, more aggressive and wider use of HMG-CoA reductase inhibitors should be employed in reducing elevated plasma cholesterol levels.

The use of HMG-CoA reductase inhibitors to prevent accelerated graft atherosclerosis in heart transplant patients.

Initial trials hint that HMG-CoA reductase inhibitors may have a role in preventing or retarding the progression of AGAS. Whether the potential of HMG-CoA reductase inhibitors to prevent AGAS is due to their lipid-lowering effect, immunomodulating properties, or a combination of both is also not completely known at present. Further study is needed to fully identify their mode of preventing AGAS and, more important, to determine their usefulness and role in preventing AGAS, especially since concurrent HMG-CoA reductase inhibitor use with cyclosporine is not innocuous. Potential for a pharmacokinetic drug interaction, which results in an elevation of HMG-CoA reductase inhibitor concentrations, exists when these two agents are used together, thus increasing the potential for the HMG-CoA reductase inhibitor to cause musculoskeletal complications. When such combination therapy is used, the likelihood of this interaction can be reduced by prescribing the HMG-CoA reductase inhibitor conservatively--using the smallest effective dose and increasing the daily dosage slowly. Although the risk of musculoskeletal toxicity exists at any HMG-CoA reductase inhibitor dosage, most patients should be able to tolerate daily dosages of up to 20 mg of lovastatin, 10 mg of simvastatin, and 40 mg of pravastatin. Patients also need to be made aware of and monitored for musculoskeletal symptoms suggestive of myositis and/or myalgias. In addition, the avoidance of elevated cyclosporine concentrations and when practical, monitoring of HMG-CoA reductase inhibitor concentrations are recommended.

Reducing costs by reducing lipid levels in CHD

There is now good evidence to support the use of HMG-CoA reductase inhibitors in the primary and secondary prevention of coronary heart disease (CHD). It is thought that the maximum benefit of such treatment can only be obtained with life-long treatment. Since these drugs are expensive, their use is now being scrutinised from a cost-effectiveness point of view, as discussed at the 18th Congress of the European Society of Cardiology (ESC) [ Birmingham, UK; August 1996 ]. As a comparison, the cost-effectiveness of tocopherol [vitamin E] in people with proven atherosclerosis was also discussed.

Reserve HMG CoA reductase inhibitor use for high-risk patients

Reserve HMG CoA reductase inhibitor use for high-risk patients

HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein-expressing cells.

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, involved in de novo cholesterol synthesis and cell-cycle progression, was identified as a potential mediator of the growth inhibitory effects of retinoic acid on human neuroblastoma. Lovastatin, a nonreversible inhibitor of HMG-CoA reductase, induced extensive cytotoxicity that was restricted to drug-resistant P-glycoprotein-expressing neuroblastoma cell lines. This response was potentiated by dibutyryl cyclic AMP but not retinoic acid. Patients with advanced-stage metastatic neuroblastoma often display an acquired chemoresistant phenotype, which may in part be mediated by P-glycoprotein. Our studies support the application or use of HMG-CoA reductase inhibitors as potential therapeutic agents in the treatment of these patients who are refractory to chemotherapy.

The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease

3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce biliary cholesterol saturation index (CSI) in duodenal bile in hypercholesterolemic patients and might be useful for gallstone dissolution. However, preliminary data suggest that these drugs are not effective in this respect. We therefore studied 33 patients with radiolucent gallstones in an opacifying gallbladder who were scheduled for elective cholecystectomy. Patients were treated with 40 mg pravastatin day −1 or placebo during the 3 weeks before surgery. Six patients could not be evaluated. Baseline characteristics (age, sex, body mass index, serum cholesterol, and the solitary/multiple gallstone ratio) were similar in both groups. Serum cholesterol fell by 39% in the pravastatin group ( P < .001) and remained unchanged in the placebo group. Biliary cholesterol (9.5 ± 1.3 vs. 14.3 ± 1.5 mmol/L, P = .026), and phospholipid concentrations (24.8 ± 3.9 vs. 36.7 ± 3.9 mmol/L, P = .043) were lower in the pravastatin group. Although bile salt concentrations were lower in the pravastatin group (114 ± 21 vs. 152 ± 15 mmol/L), this difference was not significant. CSI was not different between both groups (142 ± 27% [pravastatin]vs. 113 ± 6% [placebo], P = NS). Cholesterol crystals were present in fresh bile in 7 of 13 patients in the pravastatin group and in 11 of 14 controls ( P = NS). Nucleation time was comparable between the 2 groups (13 ± 3 vs. 9 ± 3 days, P = NS). Bile salt species and molecular species of phospholipids determined with high-performance liquid chromatography did not differ either between both groups. Not only cholesterol but also phospholipid concentrations decrease in gallbladder bile during pravastatin treatment in cholesterol gallstone patients, with comparable CSI and nucleation time. This study does not support the use of HMG-CoA reductase inhibitors for dissolution of cholesterol gallstones.

Dyslipidemias in diabetic patients

Optimum care of diabetic patients should include screening for lipid abnormalities. The combination of high triglyceride and low high-density lipoprotein cholesterol levels, which is common in non-insulin-dependent (type II) diabetes, should be considered a separate risk factor for coronary artery disease. Pharmacologic therapy for dyslipidemias should be considered early in diabetic patients with atherosclerotic disease that has not responded to hygienic measures, including diet, exercise, and smoking cessation. Use of HMG-CoA reductase inhibitors and gemfibrozil (Lopid) may be more appropriate for treatment of diabetic dyslipidemias than niacin or bile acid-binding resins.

HMG-CoA reductase inhibitor use in the aged. A review of clinical experience.

While the benefit of cholesterol-lowering in the elderly has yet to be proven in clinical trials, individuals at high risk of coronary events who otherwise enjoy a good quality of life, should not be denied cholesterol-lowering therapy on the basis of age alone. Moreover, hypolipidaemic drugs are already extensively used in the aged. The HMG-CoA reductase inhibitors lovastatin, simvastatin and pravastatin are potent well tolerated hypolipidaemic therapies in young subjects. Although there have been few studies on their use in elderly subjects, the available data suggest the efficacy and safety of HMG-CoA reductase inhibitors in similar to that established for younger age groups.

The use of HMG-CoA reductase inhibitors in hyperlipidaemia

The use of HMG-CoA reductase inhibitors in hyperlipidaemia