Intensive Lipid-Lowering Therapy Following Acute Coronary Syndrome: The Earlier the Better
Abstract
1. Introduction
1.1. Cardiovascular Risk Post-PCI/ACS
1.2. LDL Targets
1.3. Current Status of Lipid (LDL-C)-Lowering
1.4. Benefits Beyond Statins Monotherapy
1.5. Lipid-Lowering in a Special Scenario—Kidney Disease
1.6. Lipid-Lowering in Primary vs. Secondary Prevention
1.7. Early and Intensive Lipid-Lowering
2. Conclusions
- Guidelines should mandate baseline lipid testing during admission for ACS/PCI.
- Early initiation of intensive lipid-lowering therapy is necessary. This may involve starting combination therapy (dual or even triple) up front after ACS/PCI, depending on the baseline LDL-C levels, rather than relying on a gradual escalation approach. This approach is supported by recent consensus statements.
- Individualized lipid targets should be explained to every patient, and closer follow-up is needed to ensure targets are met and allow for timely therapy intensification.
- Efforts should be made to overcome clinical inertia regarding the use of adjuvant lipid-lowering agents beyond statins and address concerns about high-dose statin side effects that lead to under-treatment or early discontinuation.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Therapy | Mechanism | Advantages | Limitations | Key Trials |
---|---|---|---|---|
High-intensity statin | HMG-CoA inhibition | Low cost, mortality benefit | Myopathy, diabetes risk | A to Z, PROVE-IT TIMI 22, IDEAL |
Ezetimibe | NPC1L1 inhibition | Additive 20–24% LDL-C reduction | Modest efficacy alone | IMPROVE-IT |
PCSK9 inhibitor monoclonal antibody | LDL-R upregulation | 53% LDL-C reduction, plaque regression | Cost, injection site reactions | FOURIER, ODYSSEY-Outcomes |
Bempedoic acid | ACL inhibition | Oral, no muscle toxicity | Gout, limited outcome data | CLEAR Outcomes |
Icosapent ethyl | TG reduction | 20% reduction in CVD | No LDL-C lowering | REDUCE-IT |
Trial/ Registry | Timing of Intervention | Population/ Setting | Lipid-Lowering Strategy | Main Outcomes/Findings | Early vs. Late Insights |
---|---|---|---|---|---|
LAI-REACT [47] | Early (immediate) | Statin-naive ACS patients | Triple therapy: rosuvastatin, ezetimibe, bempedoic acid (REB) | Rapid and sustained LDL-C reduction: 59.3%, 62.3%, 61.6%, and 59.7%, at weeks 1, 2, 4, and 6, respectively (p < 0.001). Target LDL-C < 50 mg/dL achieved in 61.3% in first week, 72.9% in second week, 69.2% in third week, and 65.1% in fourth week. | Triple REB therapy quickly and effectively lowers LDL-C after ACS, with significant reductions seen in one week and maintained for six weeks. |
EVOPACS [34] | Early (within 24 h) | ACS patients | PCSK9 inhibitor (evolocumab + high-intensity statins | Target levels achieved in >95% patients until 8 weeks. Combination therapy was safe and effective. | Early combination therapy helped in achieving recommended LDL targets early and was safe. |
SWEDE-HEART REGISTRY [50] | Early vs. late (Registry) | Swedish ACS/MI patients | Statins + ezetimibe
| Early ezetimibe initiation linked to reduced mortality. | Early combination therapy was associated with a lower risk of major adverse cardiovascular events (MACE—including death, MI, and stroke) and cardiovascular death compared to delayed or no ezetimibe. |
PACMAN-MI [11] | Early | Post-MI, early post-event | PCSK9 inhibitor (alirocumab) + statin | Early PCSK9 inhibitor reduces plaque volume and improves stabilization in acute MI patients. | Early lowering improves plaque regression. |
HUYGENS [12] | Early | Post-MI, early post-event | PCSK9 inhibitor (alirocumab) + statin | Early PCSK9 inhibitor improves plaque characteristics and reduces inflammation. | Early intervention shows favorable vascular effects. |
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Pradhan, A.; Sharma, P.; Prajapathi, S.; Aracri, M.; Iellamo, F.; Perrone, M.A. Intensive Lipid-Lowering Therapy Following Acute Coronary Syndrome: The Earlier the Better. J. Cardiovasc. Dev. Dis. 2025, 12, 300. https://doi.org/10.3390/jcdd12080300
Pradhan A, Sharma P, Prajapathi S, Aracri M, Iellamo F, Perrone MA. Intensive Lipid-Lowering Therapy Following Acute Coronary Syndrome: The Earlier the Better. Journal of Cardiovascular Development and Disease. 2025; 12(8):300. https://doi.org/10.3390/jcdd12080300
Chicago/Turabian StylePradhan, Akshyaya, Prachi Sharma, Sudesh Prajapathi, Maurizio Aracri, Ferdinando Iellamo, and Marco Alfonso Perrone. 2025. "Intensive Lipid-Lowering Therapy Following Acute Coronary Syndrome: The Earlier the Better" Journal of Cardiovascular Development and Disease 12, no. 8: 300. https://doi.org/10.3390/jcdd12080300
APA StylePradhan, A., Sharma, P., Prajapathi, S., Aracri, M., Iellamo, F., & Perrone, M. A. (2025). Intensive Lipid-Lowering Therapy Following Acute Coronary Syndrome: The Earlier the Better. Journal of Cardiovascular Development and Disease, 12(8), 300. https://doi.org/10.3390/jcdd12080300