LDL Management in Acute Coronary Syndrome: FOURIER Trial and Current Guidelines
All patients with acute coronary syndrome should receive high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) immediately before hospital discharge, with the target LDL-C <55 mg/dL; if LDL-C remains ≥70 mg/dL on maximally tolerated statin plus ezetimibe, add a PCSK9 inhibitor. 1
Immediate In-Hospital Management
Initiate high-intensity statin therapy before discharge in all ACS patients regardless of baseline LDL-C, as this reduces major vascular events by approximately 15% compared to moderate-intensity statins. 1
High-intensity statins lower LDL-C by ≥50% and include atorvastatin 40–80 mg daily or rosuvastatin 20–40 mg daily. 1
The benefit of high-intensity statins appears early after ACS and persists over time, with no indication of safety concerns from achieving very low LDL-C concentrations. 1
Consider concurrent addition of ezetimibe at hospital discharge (Class 2b recommendation) in very high-risk ACS patients, as this may accelerate achievement of LDL-C goals. 1, 2
Post-Discharge Treatment Algorithm Based on LDL-C Levels
Reassess lipid profile 4–8 weeks after discharge and adjust therapy as follows: 1
If LDL-C <55 mg/dL on maximally tolerated statin:
- Continue high-intensity statin therapy without adding non-statin agents. 2
- Do not de-escalate statin therapy during follow-up in patients tolerating treatment. 1
If LDL-C 55–69 mg/dL on maximally tolerated statin:
- Adding a non-statin agent is reasonable (Class 2a recommendation, Level B-R evidence). 1, 2
- Ezetimibe provides an additional 15–25% LDL-C reduction beyond statin monotherapy. 3, 2
If LDL-C ≥70 mg/dL on maximally tolerated statin:
- Add ezetimibe 10 mg daily (Class 1 recommendation, Level A evidence). 1
- Ezetimibe blocks intestinal cholesterol absorption via the NPC1L1 protein and reduces cardiovascular events in post-ACS patients. 2, 4
If LDL-C remains ≥70 mg/dL on maximally tolerated statin plus ezetimibe:
- Add a PCSK9 inhibitor (evolocumab 140 mg every 2 weeks or 420 mg monthly, or alirocumab) following clinician–patient discussion about net benefit, safety, and cost. 1
- PCSK9 inhibitors reduce LDL-C by an additional 50–60% and reduce major adverse cardiovascular events by 15% over 2–3 years. 1, 2, 5
FOURIER Trial Evidence
The FOURIER trial (N=27,564) demonstrated that evolocumab added to maximally tolerated statin therapy (±ezetimibe) in patients with established cardiovascular disease significantly reduced cardiovascular events: 6
Primary composite endpoint (cardiovascular death, MI, stroke, coronary revascularization, or hospitalization for unstable angina): hazard ratio 0.85 (95% CI: 0.79–0.92; p<0.0001). 6
Key secondary composite endpoint (cardiovascular death, MI, or stroke): hazard ratio 0.80 (95% CI: 0.73–0.88; p<0.0001). 6
Median LDL-C achieved at Week 48 was 26 mg/dL, with 47% of patients achieving LDL-C <25 mg/dL. 6
Greater absolute benefit was demonstrated in patients enrolled closer to their ACS event. 1
The median follow-up was 26 months, with 99.2% of patients followed until trial end or death. 6
Statin-Intolerant Patients
Non-statin lipid-lowering therapy is mandated (Class 1 recommendation) for statin-intolerant patients. 2
Bempedoic acid emerges as the preferred option with outcomes data, reducing MACE by 13% in statin-intolerant patients. 2, 7
Bempedoic acid 180 mg daily provides 15–25% LDL-C reduction with minimal muscle-related adverse effects because it is activated only in the liver. 2, 7
PCSK9 inhibitors are safe and well tolerated in statin-intolerant patients, though outcomes studies as monotherapy are not available. 1
Critical Safety Monitoring
Monitor hepatic transaminases before and during treatment, particularly when combining ezetimibe with statins. 3
Monitor for elevated uric acid levels and gout risk with bempedoic acid. 2, 7
No safety concerns exist for achieving very low LDL-C concentrations on statins or other lipid-lowering therapies. 1
Myopathy and rhabdomyolysis are rare with ezetimibe alone or in combination with statin therapy. 3
Common Pitfalls to Avoid
Do not use moderate-intensity statins as primary therapy for ACS patients, as they provide suboptimal protection compared with high-intensity regimens. 3
Do not delay intensification of lipid therapy in patients not achieving LDL-C <55 mg/dL, as therapeutic inertia is a major contributor to suboptimal outcomes. 7
Do not accept LDL-C ≥70 mg/dL as adequate in post-ACS patients, as this leaves substantial residual cardiovascular risk. 7
Only 22% of very high-risk secondary prevention patients in Europe meet LDL-C targets <55 mg/dL, highlighting the need for aggressive therapy escalation. 2
Do not add non-statin agents before maximizing statin intensity, except when high-intensity statins are not tolerated. 3