Determining When to Add Nonstatin Therapy: A Quantitative Approach.

Area of Science:

• Cardiology
• Pharmacoeconomics
• Preventive Medicine

Background:

• Nonstatin therapies for cardiovascular disease are underutilized due to cost and uncertain benefits.
• Identifying patient subgroups who benefit most from add-on therapy is crucial.

Purpose of the Study:

• To identify patients who may benefit from adding nonstatin therapy to background statin treatment.
• To evaluate the cost-effectiveness of ezetimibe and PCSK9 monoclonal antibodies in high-risk populations.

Main Methods:

• Systematic reviews of subgroup analyses from randomized trials and observational studies were conducted.
• Estimated 10-year absolute risk of atherosclerotic cardiovascular disease (ASCVD) was determined for statin-treated patients.
• Number needed to treat (NNT) to prevent one ASCVD event over 5 years was calculated for different patient groups and LDL-C levels.

Main Results:

• Very high-risk patients (ASCVD risk ≥30%) and high-risk patients (ASCVD risk 20-29%) were defined.
• Adding ezetimibe achieved NNT ≤50 for very high-risk patients with LDL-C ≥130 mg/dL or high-risk patients with LDL-C ≥190 mg/dL.
• Adding PCSK9 inhibitors achieved NNT ≤50 for very high-risk and high-risk patients with LDL-C ≥70 mg/dL.

Conclusions:

• Ezetimibe and PCSK9 monoclonal antibodies may be cost-effective additions to maximally tolerated statin therapy.
• Cost-effectiveness is dependent on baseline low-density lipoprotein cholesterol (LDL-C) levels in very high- and high-risk patients.
• These findings support personalized treatment strategies for ASCVD prevention.