What are the guidelines for determining average, high, and very high risk for cardiac events in patients with Atherosclerotic Cardiovascular Disease (ASCVD) and considering statin use?

From the Guidelines

Patients with Atherosclerotic Cardiovascular Disease (ASCVD) are categorized into average, high, and very high risk groups based on clinical factors and history, with very high-risk patients having a history of multiple major ASCVD events or one major event with multiple high-risk conditions, and should be treated with high-intensity statins to reduce LDL-C by ≥50% and achieve levels <70 mg/dL, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1. The guidelines for determining cardiovascular risk in patients with ASCVD consider several factors, including clinical ASCVD, diabetes mellitus, LDL-C levels, and risk-enhancing factors such as family history of premature ASCVD, persistently elevated LDL-C levels, metabolic syndrome, chronic kidney disease, and history of preeclampsia or premature menopause 1.

• High-risk patients include those with multiple major ASCVD events or one major event with multiple high-risk conditions, such as diabetes, age ≥65, hypertension, CKD, smoking, persistent elevated LDL-C, or heart failure.
• Very high-risk patients have a history of multiple major ASCVD events or one major event with multiple high-risk conditions.
• For statin therapy, high-intensity statins (atorvastatin 40-80mg or rosuvastatin 20-40mg daily) are recommended for very high-risk patients, with a goal of reducing LDL-C by ≥50% and achieving levels <70 mg/dL.
• For high-risk patients, high-intensity statins are recommended with an LDL-C goal of <100 mg/dL.
• Average-risk patients should receive at least moderate-intensity statins (atorvastatin 10-20mg, rosuvastatin 5-10mg, simvastatin 20-40mg, or pravastatin 40-80mg daily) with an LDL-C goal of <100 mg/dL. The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol recommends that in patients with clinical ASCVD, high-intensity statin therapy or maximally tolerated statin therapy should be used to reduce LDL-C levels, with a goal of reducing LDL-C by ≥50% and achieving levels <70 mg/dL for very high-risk patients 1.
• The guideline also recommends that in patients with clinical ASCVD who are judged to be very high risk and are on maximally tolerated LDL-C lowering therapy with LDL-C 70 mg/dL or higher, it is reasonable to add a PCSK9 inhibitor following a clinician–patient discussion about the net benefit, safety, and cost.
• In patients with clinical ASCVD who are on maximally tolerated statin therapy and are judged to be at very high risk and have an LDL-C level of 70 mg/dL or higher, it is reasonable to add ezetimibe therapy. The guidelines emphasize the importance of lifestyle therapy, including a healthy diet, regular physical activity, and weight management, in addition to statin therapy, to reduce the risk of ASCVD events 1.
• The guidelines also recommend that clinicians consider the potential benefits and risks of statin therapy, as well as patient preferences and values, when making decisions about treatment.
• The guidelines emphasize the importance of regular monitoring of LDL-C levels and adjustment of statin therapy as needed to achieve the recommended LDL-C goals.

From the FDA Drug Label

The JUPITER study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL-C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%).

The guidelines for determining average, high, and very high risk for cardiac events in patients with Atherosclerotic Cardiovascular Disease (ASCVD) and considering statin use are not directly stated in the provided drug label. However, the label mentions the Framingham risk criteria, which is a tool used to estimate the 10-year cardiovascular risk of an individual.

• High risk is often defined as a 10-year cardiovascular risk of ≥10% to <20%
• Very high risk is often defined as a 10-year cardiovascular risk of ≥20%. It is essential to consult the original Framingham risk criteria or other relevant guidelines for a more accurate assessment of cardiac risk. 2

From the Research

Guidelines for Determining Cardiac Event Risk

The guidelines for determining average, high, and very high risk for cardiac events in patients with Atherosclerotic Cardiovascular Disease (ASCVD) and considering statin use are as follows:

• Average risk: Patients with a 10-year ASCVD risk score of less than 7.5% are considered to be at average risk for cardiac events 3.
• High risk: Patients with a 10-year ASCVD risk score of 7.5% to 20% are considered to be at high risk for cardiac events 3.
• Very high risk: Patients with a 10-year ASCVD risk score of greater than 20% are considered to be at very high risk for cardiac events 3.

Considerations for Statin Use

When considering statin use, the following factors should be taken into account:

• Patients with established ASCVD who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe may be considered for PCSK9 inhibitor therapy 4.
• The use of PCSK9 inhibitors as adjunct to statin therapy can reduce LDL-C by 50-60% above that achieved by statin therapy alone 5, 4.
• The cost-effectiveness of PCSK9 inhibitor therapy is limited to secondary prevention in high-risk patients 4.

Risk Assessment and Management

The assessment and management of cardiac event risk should involve the following:

• Calculation of the 10-year ASCVD risk score using an estimator developed by the American College of Cardiology/American Heart Association (ACC/AHA) 6.
• Evaluation of the temporal change in 10-year ASCVD risk over a period of 4 to 5 years to reflect success or failure in controlling major cardiovascular risk factors 7.
• Targeted interventions to modify risk factors, such as blood pressure and blood sugar control, in patients at intermediate and high risk of developing ASCVD 6.