If a patient is already on high-intensity statin therapy with a low-density lipoprotein (LDL) level near target, are we just chasing numbers by considering additional therapies to further reduce their cardiovascular risk?

You Are Not Just Chasing Numbers—Further Risk Reduction Is Achievable and Beneficial

Even when a patient is on high-intensity statin therapy with LDL-C near target, adding nonstatin therapies provides meaningful cardiovascular risk reduction, particularly in very high-risk patients. This is not merely "chasing numbers"—it's reducing morbidity and mortality.

The Evidence Against "Just Chasing Numbers"

The concept that achieving LDL-C goals on high-intensity statins represents the ceiling of benefit has been definitively refuted:

• For patients with clinical ASCVD at very high risk on maximally tolerated statin therapy with LDL-C ≥70 mg/dL, adding ezetimibe reduces major adverse cardiovascular events (MACE) 1
• The 2022 ACC Expert Consensus recommends a lower LDL-C threshold of ≥55 mg/dL (or non-HDL-C ≥85 mg/dL) for considering nonstatin therapies in very high-risk patients, reflecting evidence that individuals achieving LDL-C <55 mg/dL experience lower event rates than those with higher levels 1
• There appears to be no LDL-C level below which cardiovascular benefit ceases—lifelong very low LDL-C levels (15-30 mg/dL) in patients with genetic conditions and in clinical trials show lower ASCVD incidence without adverse effects 1

The Log-Linear Relationship: Every Point Counts

The relationship between LDL-C and cardiovascular risk is log-linear without an apparent threshold:

• For every 1% reduction in LDL-C levels, relative risk for major coronary events is reduced by approximately 1%, and this relationship holds even for LDL-C levels below 100 mg/dL 1
• Recent trials did not identify a threshold LDL-C level below which no further reduction in risk occurs 1
• Reducing LDL-C by 30% starting at 100 mg/dL produces another 20-30% lowering in relative risk for coronary heart disease 1

Defining "Very High Risk" Patients Who Benefit Most

Not all patients require aggressive add-on therapy, but very high-risk patients clearly benefit:

Very high-risk characteristics include 1:

• History of multiple major ASCVD events
• One major ASCVD event plus multiple high-risk conditions
• Recent acute coronary syndrome (within 2 years)
• Baseline LDL-C ≥190 mg/dL with clinical ASCVD
• Diabetes with additional cardiovascular risk factors

For these patients, intensive LDL lowering to <70 mg/dL (and consideration of <55 mg/dL) is supported by outcomes data, not arbitrary number-chasing 1.

Practical Treatment Algorithm for Patients Already on High-Intensity Statins

Step 1: Verify Optimal Statin Therapy

• Confirm the patient is on maximally tolerated high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) 1
• Assess adherence to medications and lifestyle modifications 1
• Exclude secondary causes of hyperlipidemia (hypothyroidism, nephrotic syndrome, medications) 1

Step 2: Risk Stratification

If the patient has clinical ASCVD at very high risk AND:

• LDL-C ≥55 mg/dL (or non-HDL-C ≥85 mg/dL) → Consider adding nonstatin therapy 1
• LDL-C ≥70 mg/dL → Adding ezetimibe is reasonable (Class 2a recommendation) 1

If the patient has clinical ASCVD (not very high risk) AND:

• LDL-C ≥70 mg/dL → Consider adding ezetimibe 1

Step 3: Nonstatin Therapy Selection

First-line nonstatin agent:

• Ezetimibe provides an additional 15-25% LDL-C reduction when added to statin therapy 2
• Ezetimibe added to ongoing statin therapy significantly lowers total-C, LDL-C, Apo B, and non-HDL-C (mean LDL-C reduction of 25% beyond statin alone) 2

If LDL-C remains ≥70 mg/dL on maximally tolerated statin plus ezetimibe:

• PCSK9 monoclonal antibodies can be beneficial to further reduce MACE risk (Class 2a recommendation) 1
• PCSK9 inhibitors provide 50-60% additional LDL-C lowering 3

Alternative considerations:

• Bempedoic acid may be considered as an alternative or addition 1
• Inclisiran may be considered for patients with poor adherence to PCSK9 mAbs (twice-yearly dosing), but cardiovascular outcomes trials are pending 1

Step 4: Monitoring

• Assess lipid response 4-12 weeks after adding therapy, then every 3-12 months 1
• Continue monitoring adherence to lifestyle modifications and medications 1

Common Pitfalls to Avoid

Pitfall 1: Assuming LDL-C <100 mg/dL is "good enough"

• The 2004 ATP III update explicitly stated that <100 mg/dL was a minimal goal, not the level of maximal benefit 1
• For very high-risk patients, an optional LDL-C goal of <70 mg/dL (now <55 mg/dL) provides additional absolute risk reduction 1

Pitfall 2: Focusing solely on LDL-C percentage reduction

• Both percentage reduction (≥50%) AND absolute LDL-C thresholds matter 1
• A patient achieving 50% reduction but still with LDL-C of 80 mg/dL may benefit from further lowering if at very high risk

Pitfall 3: Delaying nonstatin therapy due to cost concerns

• The cardiovascular outcomes benefit of ezetimibe and PCSK9 inhibitors in very high-risk patients is established 1
• Generic ezetimibe is now widely available and cost-effective

Pitfall 4: Not considering apolipoprotein B (apoB) testing

• ApoB provides superior assessment of residual cardiovascular risk in statin-treated patients compared to LDL-C alone, particularly in those with elevated triglycerides or low HDL-C 4
• If apoB is elevated despite LDL-C near target, this indicates residual risk and should prompt discussion about add-on therapy 4

The Bottom Line

You are not "just chasing numbers" when you intensify therapy in a patient already on high-intensity statins with LDL-C near target. The evidence clearly demonstrates that:

• Lower is better, with no apparent threshold for benefit 1
• Very high-risk patients derive meaningful MACE reduction from achieving LDL-C <70 mg/dL (ideally <55 mg/dL) 1
• Ezetimibe added to statin therapy reduces cardiovascular events, not just LDL-C numbers 1
• The 2025 ACC/AHA performance measures explicitly recommend nonstatin therapy for very high-risk patients with LDL-C ≥70 mg/dL on maximally tolerated statins 1

The goal is reducing heart attacks, strokes, and cardiovascular death—outcomes that matter to patients—not arbitrary numerical targets.