ReviewClinically relevant differences between the statins: implications for therapeutic selection
Section snippets
Lipid-lowering effects
All statins lower cholesterol levels through reversible and competitive inhibition of HMG-CoA reductase, an enzyme involved in the biosynthesis of cholesterol and other sterols. This mechanism of action and its effect on lipids (LDL cholesterol reduction, triglyceride reduction, and high-density lipoprotein [HDL] cholesterol elevation) are well established 2, 4. The synthetic statins atorvastatin, cerivastatin, and fluvastatin appear to be as efficacious as the natural ones, such as lovastatin,
Pharmacokinetic properties
Some pharmacokinetic differences may suffice to affect the choice of one statin over another in a given clinical situation (Table 2) 6, 7, 8, 9, 10, 11, 26, 27. The bioavailability of the statins varies from less than 5% with simvastatin to approximately 60% with cerivastatin; absorption varies from 30% with lovastatin to 98% with fluvastatin. Except for pravastatin, all statins are subject to extensive first-pass metabolism by the cytochrome P450 (CYP450) enzyme system 6, 7, 8, 9, 10, 11, 26,
Drug interactions
The statins are involved in a number of pharmacokinetic and pharmacodynamic drug interactions (Table 3) 6, 7, 8, 9, 10, 11, 26, 27, 28, 29, 39. All of the currently available statins, except pravastatin, are metabolized by the CYP450 system figuring prominently in their interaction profiles. Atorvastatin, lovastatin, and simvastatin are metabolized by CYP3A4, whereas fluvastatin is metabolized by the CYP2C9 isoenzyme. Cerivastatin is jointly metabolized by CYP3A4 and CYP2C8. Pravastatin does
Evidence from clinical trials
Large, randomized clinical trials of long duration have demonstrated the safety and efficacy of the statins lovastatin, simvastatin, and pravastatin in patients at high and low risk of coronary heart disease and with a wide range of baseline cholesterol levels 4, 5, 12, 21, 58, 59, 60, 61, 62, 63, 64. These clinical trials suggest that moderate reductions of 25% to 28% in LDL cholesterol levels can result in a 25% to 35% reduction in clinical events, even though the majority of patients do not
Other potential therapeutic applications
In addition to reducing the risk of cardiovascular morbidity and mortality, statins have demonstrated the ability to prevent stroke 5, 58, 59, 60, 68, 76, 77, 78, 79, 80 and reduce the development of peripheral vascular disease 69, 81. Other potential uses for statins may include essential hypertension (82), colon cancer (83), osteoporotic fracture 84, 85, 86, ventricular arrhythmia (87), immune response (88), and dementia (89). Further investigation is required before any clinical
Safety and tolerability
Statin monotherapy is associated with few adverse effects, the most serious being hepatic and skeletal muscle toxicity 6, 7, 8, 9, 10, 11, 26, 27, 28, 29, 35. Elevated transaminase levels (greater than three times the upper limit of normal) occur in approximately 1% of patients treated, regardless of which statin and dose relation (64). Because of the risk of liver toxicity, manufacturers recommended that transaminase levels be monitored according to their package labeling. Elevated
Pharmacoeconomics
Pharmacoeconomic considerations affect the statin-prescribing decision in at least two ways: cost-effectiveness analyses can determine if a patient should be treated with a statin, and cost-minimization analyses can determine which statin to use. Because most patients will require lifelong therapy, the cost of statin therapy can be substantial both to patients and health care systems, although most analyses find statin therapy to be reasonably cost effective in terms of dollars per life-year or
Conclusion and recommendations
Figure 1 presents a general approach for initial statin selection based on a patient’s risk stratification. High-risk patients include those with type 2 diabetes, symptomatic peripheral vascular disease, abdominal aortic aneurysm, or carotid artery disease. These patients are candidates for primary prevention with a goal of reducing LDL cholesterol levels to 100 mg/dL or less 3, 64, 99. In patients with established coronary disease, the risk of future coronary events is 20% or greater per
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