What safety issues should be considered when taking statins to lower blood lipids?

What precautions should be taken when taking statins?

Statins can be taken at any time, once daily. However, taking them at night slightly increases the reduction in LDL-C. Once the desired therapeutic effect is achieved, long-term use of statins should be continued, and discontinuation should be avoided if tolerated. Studies suggest that discontinuing statins may increase the incidence of cardiovascular events. If adverse reactions occur after using statins, they can be managed by switching to another statin, reducing the dose, taking it every other day, or switching to a non-statin lipid-lowering drug.

Most people tolerate statins well. Adverse reactions are more common in those receiving high-dose statin therapy, commonly manifesting as abnormal liver function, mainly elevated transaminases, with an incidence of 0.5%–3.0%, showing a dose-dependent effect. Patients with serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels exceeding three times the upper limit of normal, or those with concurrent elevated total bilirubin, should have their dosage reduced or discontinued. For patients with transaminase elevations within three times the upper limit of normal, observation can be conducted at the original or reduced dose; in some patients, transaminase levels may return to normal after this treatment. Decompensated cirrhosis and acute liver failure are contraindications for statin use.

Approximately 5% of patients taking statins may develop myopathy, including myalgia, myositis, and rhabdomyolysis. Myalgia presents as muscle pain or weakness without elevated creatine kinase (CK). Asymptomatic cases often present with mild CK elevation. Myositis is characterized by muscle symptoms accompanied by elevated CK. Rhabdomyolysis is characterized by muscle symptoms such as pain, tenderness, and weakness, accompanied by a significant increase in CK levels (more than 10 times the upper limit of normal) and elevated creatinine, often accompanied by brown urine and myoglobinuria. This is the most dangerous adverse reaction to statins, and in severe cases, it can be fatal. If such symptoms are observed, the medication should be discontinued immediately. Myositis most commonly occurs in patients with multiple diseases and/or those using multiple medications. Myositis rarely occurs with standard-dose statin therapy alone.

Some patients may have mild to moderate CK elevations without muscle discomfort. Since CK elevation is not specific, careful analysis is needed to determine if it is caused by statins.

The following populations may be more prone to myopathy and should be monitored closely during use:

(1) Elderly patients (especially those >80 years old), more common in women.

(2) Patients who are thin and frail.

(3) Patients with multiple systemic diseases (such as chronic renal insufficiency, especially chronic renal insufficiency caused by diabetes).

(4) Concomitant use of multiple medications.

(5) Perioperative period.

(6) Concomitant use of the following specific medications or diets: fibrates (especially gemfibrozil), niacin (rare), cyclosporine, pyrrole antifungals, erythromycin, clamisole, HIV protease inhibitors, nefazodone (antidepressant), verapamil, amiodarone, and large amounts of grapefruit juice and alcohol abuse.

(7) Excessive dosage.

Long-term use of statins increases the risk of developing new-onset diabetes, with an incidence rate of 10%–12%, known as the "statin effect." The overall cardiovascular benefits of statins far outweigh the risk of developing new-onset diabetes. Both high-risk individuals and existing diabetic patients with indications for statin therapy should adhere to their prescribed regimen.

Statin therapy can cause cognitive impairment, but this is mostly transient and infrequent. Meta-analyses show that statins have no adverse effects on renal function.

Other adverse reactions of statins include headache, insomnia, depression, and gastrointestinal symptoms such as indigestion, diarrhea, abdominal pain, and nausea.