What are the long-term effects of taking statins (HMG-CoA reductase inhibitors)?

From the Guidelines

Statins are generally safe and effective medications for long-term use in managing cholesterol levels, though they can cause side effects in some patients. The most significant long-term benefit is reduced risk of cardiovascular events like heart attacks and strokes through lowering LDL cholesterol, as supported by a recent meta-analysis indicating that a 1 mM drop in LDL-cholesterol was associated with a 21 % drop in major vascular events 1. However, some patients may experience muscle-related side effects ranging from mild soreness to rare but serious muscle breakdown (rhabdomyolysis), with a management strategy of statin discontinuation until symptoms improve, followed by rechallenge with a reduced dose, alternative agent, or alternative dosing regimen while monitoring for recurrent symptoms 1. Other potential long-term effects include slightly increased risk of developing type 2 diabetes, particularly in those already at risk; liver enzyme elevations requiring monitoring; memory or cognitive effects in some patients; and rarely, peripheral neuropathy.

Key Considerations

• Most patients tolerate statins well long-term, with benefits typically outweighing risks for those with established cardiovascular disease or high risk factors.
• Regular monitoring through blood tests for liver function and muscle enzymes is recommended, especially in the first year of treatment, although routine measurement of CK and transaminase levels is not recommended given the unlikely impact on clinical outcomes and lack of established cost effectiveness 1.
• Patients should report persistent muscle pain, weakness, or other concerning symptoms to their healthcare provider promptly rather than discontinuing medication without consultation.
• The possibility of incident diabetes mellitus should not be a contraindication to statin therapy or indication for statin discontinuation, as the benefits of statin therapy are shown to outweigh the risks of new-onset diabetes mellitus 1.

Management of Side Effects

• In patients with statin-associated side effects, a thorough evaluation for nonstatin etiologies is warranted when significant transaminase elevation persists.
• Statins are not contraindicated in patients with increased ASCVD risk with chronic, stable liver disease, and limited data suggest potential benefit 1.
• Severe statin-associated side effects are rare, and recurrent SAMS are infrequent when a thorough reassessment and management strategy of reassess, rediscuss, and rechallenge is used.

From the FDA Drug Label

The following adverse reactions have been identified during post-approval use of atorvastatin calcium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Gastrointestinal Disorders: pancreatitis General Disorders: fatigue Hepatobiliary Disorders: fatal and non-fatal hepatic failure Immune System Disorders: anaphylaxis Injury: tendon rupture Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, myositis. There have been rare reports of immune-mediated necrotizing myopathy associated with statin use Nervous System Disorders: dizziness, peripheral neuropathy. There have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with the use of all statins. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks) There have been rare reports of new-onset or exacerbation of myasthenia gravis, including ocular myasthenia, and reports of recurrence when the same or a different statin was administered Psychiatric Disorders: depression Respiratory Disorders: interstitial lung disease Skin and Subcutaneous Tissue Disorders: angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis)

The long-term effects of taking statins (HMG-CoA reductase inhibitors) may include:

• Musculoskeletal disorders: rhabdomyolysis, myositis, and immune-mediated necrotizing myopathy
• Nervous system disorders: dizziness, peripheral neuropathy, and cognitive impairment (e.g., memory loss, forgetfulness, amnesia)
• Hepatobiliary disorders: fatal and non-fatal hepatic failure
• Psychiatric disorders: depression
• Respiratory disorders: interstitial lung disease
• Skin and subcutaneous tissue disorders: angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis)
• Gastrointestinal disorders: pancreatitis
• General disorders: fatigue
• Injury: tendon rupture
• Immune system disorders: anaphylaxis 2

From the Research

Long-term Effects of Statins

The long-term effects of taking statins, also known as HMG-CoA reductase inhibitors, have been studied extensively. Some of the key findings include:

• Reduction in cardiovascular events: Statins have been shown to reduce the frequency of cardiovascular events, such as heart attacks and strokes, in patients with coronary heart disease 3.
• Improvement in liver tests: Statins can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease 3.
• Adverse effects: Statins can cause adverse effects, such as myopathy, hepatotoxicity, peripheral neuropathy, and impaired myocardial contractility, although these effects are relatively rare 4, 5, 6.

Specific Adverse Effects

Some of the specific adverse effects of statins include:

• Myopathy: Statins can cause myopathy, which is characterized by muscle weakness and elevated creatine kinase levels 6.
• Hepatotoxicity: Statins can cause hepatotoxicity, which is characterized by increased liver enzyme levels, although this effect is usually reversible with dosage reduction or treatment withdrawal 5.
• Peripheral neuropathy: Statins can cause peripheral neuropathy, which is characterized by numbness, tingling, and weakness in the hands and feet 4.

Patient Awareness and Compliance

Patient awareness and compliance with statin treatment are important factors in determining the effectiveness of the treatment. Studies have shown that:

• Patients who are aware of the benefits and risks of statin treatment are more likely to comply with the treatment 7.
• Comprehensive information at initial prescription, initiation of statins during hospitalization, dose adjustment during follow-up, and minimal co-medication can increase patient awareness and compliance 7.