What is the role of statin (HMG-CoA reductase inhibitor) therapy in patients with normal Low-Density Lipoprotein (LDL) levels but established Coronary Artery Disease (CAD)?

From the Guidelines

Statin therapy is recommended for patients with established Coronary Artery Disease (CAD) regardless of their Low-Density Lipoprotein (LDL) levels, as it reduces cardiovascular events and mortality through both lipid-lowering and pleiotropic effects. The standard approach is to start with moderate to high-intensity statin therapy, such as atorvastatin 20-80 mg daily or rosuvastatin 10-40 mg daily, as recommended by the 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non-ST-elevation myocardial infarction 1. This recommendation is based on extensive clinical evidence showing that statins reduce major vascular events, driven by reductions in coronary death or non-fatal MI, coronary revascularization, and ischemic stroke 1.

Key Considerations

• The goal of statin therapy is to reduce LDL by at least 50% from baseline or to achieve an LDL below 70 mg/dL (or even below 55 mg/dL in very high-risk patients) 1.
• Patients should be monitored with lipid panels 4-12 weeks after starting therapy and then annually, along with liver function tests and assessment for muscle symptoms.
• Lifestyle modifications, including heart-healthy diet, regular exercise, smoking cessation, and weight management, should accompany statin therapy.
• The benefit of statins in CAD patients extends beyond simple cholesterol reduction, as they help prevent plaque progression, stabilize existing plaques, and reduce the risk of future cardiovascular events.

Evidence-Based Recommendations

• The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends treatment of patients ≤75 y of age who have clinical atherosclerotic cardiovascular disease (including those with MI) with high-intensity statin 1.
• Moderate-intensity statins are recommended in their counterparts >75 y of age and in those who have contraindications/intolerance to high-intensity regimens 1.
• The European Society of Cardiology (ESC) guidelines recommend measuring Lipoprotein(a) in patients at high risk of cardiovascular disease (CVD) and to target levels below 50 mg/dL 1.

Clinical Implications

• Statin therapy should be individualized in persons >75 y of age according to the potential for ASCVD risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences 1.
• Improved compliance with therapy is an impetus for timing the initiation of statin therapy before discharge in patients hospitalized with acute MI 1.

From the FDA Drug Label

To reduce the risk of coronary death, myocardial infarction, myocardial revascularization procedures, stroke or transient ischemic attack, and slow the progression of coronary atherosclerosis in adults with clinically evident CHD. The role of statin (HMG-CoA reductase inhibitor) therapy in patients with normal Low-Density Lipoprotein (LDL) levels but established Coronary Artery Disease (CAD) is to reduce the risk of coronary death, myocardial infarction, and other cardiovascular events.

• The therapy is indicated for adults with clinically evident CHD, regardless of their LDL levels.
• The goal is to slow the progression of coronary atherosclerosis and reduce the risk of cardiovascular mortality 2.

From the Research

Role of Statin Therapy in Patients with Normal LDL Levels but Established CAD

• The use of statin therapy in patients with established Coronary Artery Disease (CAD) and normal Low-Density Lipoprotein (LDL) levels is supported by several studies 3, 4, 5, 6, 7.
• A study published in 2023 found that a treat-to-target strategy with an LDL-C goal of 50-70 mg/dL was noninferior to high-intensity statin therapy for reducing the risk of major adverse cardiovascular events in patients with CAD 4.
• Another study published in 2018 found that high-intensity statins were associated with a lower risk of major adverse cardiovascular events compared to non-high-intensity statins in patients achieving treatment target for LDL-C after percutaneous coronary intervention 5.
• The importance of LDL cholesterol reduction for primary and secondary prevention of CAD events is well established, and statin therapy is a key component of this approach 3, 7.
• However, it is also noted that even with substantial reductions in LDL cholesterol, statins do not entirely eliminate CAD events, suggesting that other lipid parameters and risk factors also influence CAD risk 7.

Key Findings

• High-intensity statin therapy may be beneficial for patients with CAD, even if they have normal LDL levels 4, 5.
• A treat-to-target strategy with an LDL-C goal of 50-70 mg/dL may be an effective approach for reducing the risk of major adverse cardiovascular events in patients with CAD 4.
• The use of statin therapy should be individualized based on a patient's risk factor profile and baseline LDL-C level 3.
• Other lipid parameters, such as high-density lipoprotein (HDL) cholesterol, triglyceride, lipoprotein(a), and LDL particle size and susceptibility to oxidation, may also influence CAD risk 7.