Treatment of cholesterol problems

All patients with high LDL-C should undertake lifestyle changes with the goal of reducting serum cholesterol. Possible changes include fat loss in overweight patients, decreasing saturated and overall fat in the diet, exercise and increased consumption of plant sterols/stanols. A study of 2508 individuals, conducted by the United Kingdom Lipid Clinics concluded with diet alone, a mean body weight reduction of 1.8 percent was attained by 60% of these individuals, leading to a 5 to 7 percent reduction of LCL-C. Some experts think LDL-C can be reduced by up to thirty percent with other diets.

Patients unable to attain the required cholesterol levels with diet and exercise changes usually are put on drug therapy. Overall management of this problem can be divided into prevention, primary, and secondary. Numerous issues can arise during patient treatment of specific disorders of LDL metabolism.

An additional study of 197 men and 180 postmenopausal women diagnosed with low levels of HDL-C with moderately raised levels of LDL-C arbitrarily assigned individuals into four groups of non-treatment, aerobic exercise, exercise and diet, or simply diet. The study results indicated no group attained a significant HDL-C change, however the LDL-C reductions were significant for both women and men (20 mg/dL and 14.5 {0.52 and 0.38 mmol/L], respectively) for groups with combined exercise and diet or simply with diet, and for the group of men with diet and exercise as compared to solely exercise.

Within 6 to 12 months, the benefits of LDL-C reduction may become evident. Various factors impact an individual’s response to a cholesterol-lowering diet; genetics may impact this response, and a reduced response to dietary change as evidenced by an expanded body mass index. Short term, patients utilizing dieticians attained greater success in lowering LDL-C in comparison to patients with physician dietary counseling, long-term results for either group did not suffice. Patients meeting the above criteria should begin a hypolipidemic drug regimen.

Drug therapy. Lipid-altering agents include numerous drug classes, including bile acid sequestrants, statins, nicotinic acid, cholesterol absorption inhibitors and fibric acid derivatives. The differences exhibited in these drugs are in the action methodology, and the extent and nature of lipid lowering. The lipid abnormality will influence the particular drug prescribed. Typical dose regimens and recurrent adverse reactions, and the lipid profile range of probable changes are summarized.

Obvious improvements in overall mortality were demonstrated by the statins (a class of drugs) for primary and secondary prevention; a niacin clinical trial indicated several mortality secondary prevention benefits. Mortality benefits did not materialize during large trials of clofibrate, gemfibrozil or cholestyramine secondary benefits, but rather indicated an overall concern about increased noncardiac deaths. A significant trial with diabetic patients (some with confirmed cardiovascular disease) utilized fenofibrate which resulted in a non-significant rise in overall mortality. Gemfibrozi, utilized in a large secondary prevention trial showed a reduction in cardiac mortality, failed to demonstrate improvement in overall mortality.

Statins are the preferred choice of hypercholesterolemia patients seeking a reduction goal of primary or secondary cardiovascular risks. When statins cannot aid patients to meet LDL-C goals, the addition of ezetimibe or other agents cannot establish certainty of further clinical benefits, despite further reductions of LDL-C levels.

The choice of an additional agent when required may be influenced by abnormalities in other lipoproteins. Bile acid sequestrant or ezetimibe are sensible choices for treatment in patients having an increase in LDL-C for secondary prevention.

Secondary treatment in some patients intolerant to statins requiring secondary treatments may have options such as fenofibrate, niacin, ezetimibe, and bile acid sequestrants. For such patients, lipid specialist referrals are appropriate.

Statins. Dyslipidemia is most commonly treated with statin drugs. Statins, the most effective drugs lower LDL-C within a range of 20 to 60 percent. LDL-C was reduced by 20 to 25 percent with the use of the less potent drug fluvastatin administered at the maximum recommended dosage. The United States has approved the statins, rosuvastatin (40 mg/day) and atorvastatin (80 mg/day) as powerful for the reduction of LDL levels by approximately 60 percent. Patients with hypercholesterolemia, utilizing atorvastatin and rosuvastatin lowered triglycerides; atorvastatin lowered triglycerides from 14 to 33 percent. In raising HDL-C levels, rosuvastatin proved to be more effective than pravastatin, atorvastatin or simvastatin.

One randomized study of 180 hypercholesterolemia patients analyzed the effects of a typical diet versus a Mediterranean modified diet of dietary fiber, fruits, vegetables and rich in omega-3 fatty acids; an additional level of randomization was introduced of a placebo or simvastatin (20 mg) which was introduced after a period of twelve weeks. The analysis of results after a 24 week period, with the modified diet and drug were greater than those of the typical diet and drug (41 versus 30); apolipoprotein, B and A1 levels and triglyceride levels exhibited a similar effect.

Statins produced less frequent adverse reactions when compared with other types of lipid-lowering agents. For patients treated with a fibrate or cyclosporine, muscle injury is a significant concern; the usage of fluvastatin or pravastatin may eliminate this potential risk as CYP3A4 does not metabolize either statin.

An initial study of drug interaction interference with the activation of clopidogrel with statin therapy was indicated. Significant clinical significance of drug interaction from these randomized trials was not noted in the subgroup analysis, and changes are not recommended.