Overview of Statins for Hyperlipidemia

STATINS

Mechanism of Action:
HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids.
Indication:
Overwhelmingly the best choice for elevated LDL cholesterol, providing safe and effective LDL lowering by 18- 55%. Also, lower triglycerides, and increase HDL.
The primary target of lipid-lowering therapy is LDL because there is a strong relationship between elevated LDL and coronary heart disease. Moderate doses of statins, which primarily target LDL, decrease cardiovascular morbidity and mortality by 25% to 35% within five years’ use. Although low HDL and high triglycerides are associated with increased risk for coronary heart disease, evidence of cardiovascular benefit from treating low HDL or high triglycerides is less compelling.
Warnings/Precautions/Adverse effects:

• GI adverse effects
• Headache & dyspepsia
• Elevated liver enzymes AST and ALT.
  • Do LFT initially, at 12 weeks, then annually.
• Myopathy: is believed to be low 0.08% (8 per 10,000)

• Check CK (creatine kinase) before starting therapy. Do not stop statins if less than 3 times upper-limit of normal.
• Evaluate for increased/excess exercise.
• 30% of patients on placebo experience muscle pain
• Evaluate in 6-12 weeks as per the scheme outlined previously
• May be worse if other drugs are taken concurrently (erythromycin, cyclosporine, niacin, fibrates, antifungals)
• May lead to rhabdomyolysis: disintegration of dissolution of muscle

Drug interactions:

• Pravastatin (Pravachol®) and Rosuvastatin (Crestor®) are not metabolized by CYP450.
• Pitavastatin (Livalo®): Not significantly metabolized by CYP450 and may be less likely to be involved in drug interactions.
• Other statins (simvastatin/lovastatin) have potential for significant drug interactions.
• Grapefruit juice: co administration with grapefruit juice (8oz or 1 grapefruit)) may increase simvastatin, & lovastatin levels. Separation for food and drug does NOT work. Grapefruit primarily affects intestinal, not hepatic enzymes.

 
STATIN COMPARISONS: to get 41% LDL-C lowering:
Rosuvastatin 5mg= Atorvastatin 20mg= Simvastatin 40mg=Pravastatin 80mg
Contraindications for statins:

• Itraconazole, Ketoconazole, Posaconazole, Erythromycin, Clarithromycin, Telithromycin, HIV protease inhibitors, Nefazodone, Gemfibrozil, Cyclosporine, Danazol
• Simvastatin dose should not exceed 10 mg with amiodarone, verapamil, or diltiazem.  Simvastatin dose should not exceed 20 mg with amlodipine or ranolazine.
• Cholesterol medications are ideally dosed after supper & before bedtime, due to increased cholesterol synthesis during the night. Although rosuvastatin (Crestor®) and atorvastatin (Lipitor®), because of their long half-lives, can be dosed any time, most clinicians advise that all statins be given in the evening for maximum benefit.  Pravastatin (Pravachol®), Fluvastatin (Lescol®), Simvastatin (Zocor®) and Lovastatin (Mevacor®) must be dosed in the evening.
• May cause photosensitivity reactions.
• Pregnancy category-X.
• Asian patients may require lower doses of the statins.
• All statins except pitavastatin (Livalo®) are available generically.
• Statins are no longer recommended to be combined with niacin for hyperlipidemia. The FDA pulled approval of this combo to treat hyperlipidemia.

Statins inhibit CoQ10 formation and many theorize low CoQ10 levels might lead to myopathy. There’s no conclusive proof that CoQ10 works for statin induced myopathy but some anecdotal reports suggest it might be helpful.  Dosage: If patients want to try CoQ10, suggest starting low and dividing doses over 100 mg. Take two to three times daily to minimize nausea and diarrhea.  Interestingly enough, a meta-analysis of 2400 patients showed significant lower levels of Vitamin-D in patients who had statin associated muscle pain.
Muscle complaints defined:

• Myopathy – a general term related to any muscle complaint
• Myalgia – muscle complaints (i.e., ache, weakness) without elevations in CK. This is the most common myopathy reported with statins
• Myositis – muscle complaints with elevation of CK Rhabdomyolysis – markedly elevated levels of CK, usually greater than ten times the upper limit of normal; usually accompanied by creatinine elevation, brown urine, and urinary myoglobin.