Should patients with normal cholesterol levels take statins (HMG-CoA reductase inhibitors) to prevent strokes?

From the Guidelines

Patients with normal cholesterol levels should not take statins solely to prevent strokes unless they have other significant cardiovascular risk factors, as the potential benefits of statin therapy must be weighed against the risks, including muscle pain, liver enzyme elevations, and slightly increased risk of developing diabetes. The decision to prescribe statins should be individualized based on a comprehensive cardiovascular risk assessment, considering factors such as age, blood pressure, smoking status, and family history 1. For primary stroke prevention in people with normal cholesterol, lifestyle modifications are the first-line approach, including:

• Regular physical activity
• Maintaining a healthy weight
• Eating a heart-healthy diet
• Limiting alcohol consumption
• Avoiding tobacco Statins like atorvastatin, rosuvastatin, and simvastatin are primarily indicated for individuals with elevated cholesterol levels, established cardiovascular disease, diabetes, or multiple risk factors that place them at high risk for cardiovascular events 1. The most recent guidelines suggest that statin use for primary prevention of cardiovascular disease, including stroke, should be based on a calculated 10-year CVD event risk of 10% or greater, rather than solely on cholesterol levels 1. Additionally, the European guidelines on cardiovascular disease prevention emphasize the importance of treating plasma lipids in patients with cerebrovascular disease, as well as those with coronary artery disease or peripheral arterial disease 1.

From the FDA Drug Label

To reduce the risk of: Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD.

The FDA drug label does not directly address whether patients with normal cholesterol levels should take statins to prevent strokes. However, it does indicate that atorvastatin is used to reduce the risk of stroke in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD, and in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD 2.

Key points:

• The label mentions the use of atorvastatin to reduce the risk of stroke in specific patient populations.
• It does not explicitly state that patients with normal cholesterol levels should take statins to prevent strokes.
• The decision to prescribe statins should be based on individual patient risk factors and clinical judgment.

Given the lack of direct information in the drug label, no conclusion can be drawn regarding the use of statins in patients with normal cholesterol levels for stroke prevention.

From the Research

Statin Use for Primary Prevention of Cardiovascular Disease

• The US Preventive Services Task Force recommends that clinicians prescribe a statin for the primary prevention of CVD for adults aged 40 to 75 years who have 1 or more CVD risk factors and an estimated 10-year CVD risk of 10% or greater 3.
• For adults aged 40 to 75 years with 1 or more CVD risk factors and an estimated 10-year CVD risk of 7.5% to less than 10%, the USPSTF recommends that clinicians selectively offer a statin for the primary prevention of CVD 3.
• A review of the evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality or all-cause mortality found that statin use has at least a moderate net benefit for adults aged 40 to 75 years with no history of CVD and who have 1 or more CVD risk factors and an estimated 10-year CVD event risk of 10% or greater 3.

Efficacy of Statins in Preventing Strokes

• A systematic review and meta-analysis found that statins reduce the risk of combined fatal and non-fatal stroke (RR 0.78,95% CI 0.68 to 0.89) in people with no history of CVD 4.
• The review also found that statins reduce the risk of all-cause mortality, combined fatal and non-fatal CVD, and combined fatal and non-fatal CHD events in people with no history of CVD 4.
• Another study found that delaying statin therapy is associated with a higher risk of myocardial infarction and ischemic stroke in patients with diabetes, and that this relationship is mediated by higher low-density lipoprotein cholesterol levels 5.

Safety of Statin Therapy

• The safety of statin therapy has been extensively studied, and the evidence suggests that the benefits of statin therapy far outweigh any real or perceived risks 6.
• A review of the safety of statin therapy found that the potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment, and haemorrhagic stroke associated with the use of statins 6.
• However, the review concluded that the benefits of statin therapy in both primary and secondary prevention of cardiovascular disease are substantial, and that the long-term safety of statin therapy is well established 6.

Considerations for Patients with Normal Cholesterol Levels

• The USPSTF recommends that clinicians consider the patient's overall risk of CVD, including their age, sex, and presence of other CVD risk factors, when deciding whether to prescribe a statin for primary prevention 3.
• For patients with normal cholesterol levels, the decision to prescribe a statin should be based on their individual risk factors and overall risk of CVD, rather than their cholesterol levels alone 3, 4.