Alternate-Day Dosing With Statins

Perspective:

The following are 10 points to remember about alternate-day dosing with statins:

1. There is evidence favoring primary prevention with statins for high-risk patients. Patients with coronary disease should be treated with statins to achieve an low-density lipoprotein cholesterol (LDL-C) <100 mg/dl and <70 mg/dl for very high-risk patients.

2. While the decrease in mg/dl per mg of statin varies, the linear incremental dose response is similar with each of the statins. The percentage of patients who obtain the target LDL-C level of <100 mg/dl is 70% with 10 mg of atorvastatin, 82% with 20 mg of atorvastatin, and 89% with 40 mg of atorvastatin.

3. The efficacy of intermittent dosing of statins relates to the fact that the duration of the cholesterol-lowering effect of the statins is not related to the pharmacokinetics of the individual drug.

4. Steady-state statin drug levels may be achieved in a few days, but steady-state LDL-C reductions take several weeks to achieve, and after discontinuation, it takes several weeks before the cholesterol level returns to baseline.

5. The cholesterol-lowering action of alternate-day statins is as effective as daily dosing in many individuals.

6. To maintain the same degree of decrease in LDL-C when giving the statins on alternate days, the dose of the statins frequently needs to be increased.

7. Alternate-day statin administration seems to decrease the incidence of its adverse effects, particularly myopathy.

8. The effect of alternate-day statins on its many pleiotropic effects is unknown; thus, the efficacy for reducing cardiovascular events is not established. In small cohorts of patients, atorvastatin 20 mg daily decreases the high-sensitivity C-reactive protein (hs-CRP) by 35% compared to 22% with 20 mg atorvastatin every other day (p = 0.08), and there is no difference when baseline hs-CRP is <1 mg/dl.

9. Alternate-day dosing of statins provides cost savings.

10. Large-scale studies with outcome endpoints and prolonged follow-up are needed to substantiate the hypothesis that alternate-day statins are an equivalent strategy for reducing cardiovascular events.

Keywords: Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Coronary Disease, Lipoproteins, Heptanoic Acids, Hypercholesterolemia, Primary Prevention, Pyrroles, Cholesterol, C-Reactive Protein, Cardiovascular Diseases, Muscular Diseases


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