Effects of early protein convertase subtilisin/kexin 9 inhibitor therapy after acute coronary syndrome
After acute coronary syndrome (ACS), early use of protein convertase subtilisin/ kexin 9 (PCSK9) inhibitors is strongly recommended to help more rapidly and aggressively prevent major adverse cardiovascular events (MACEs).
Key Takeaway
PCSK9 inhibitors significantly reduce Mace in post-ACS patients; this seems to occur directly by modifying plaque composition, with subsequent stabilization, and indirectly by altering lipid metabolism and platelet aggregation.
EVACS study: More than 90% patients receiving evolocumab achieved low-density lipoprotein cholesterol (LDL Cholesterol) <55 mg/dL target (European Society of Cardiology [ESC]/European Atherosclerosis Society [EAS] guidelines); 11% patients only receiving statins attained this target.
EVOPACS study: : Evolocumab reduced LDL Cholesterol levels by 40.7% and helped 95.7% patients achieve LDL Cholesterol <55 mg/dL.
Odyssey Outcome trial: Alirocumab vs placebo reduced the overall MACE risk, reduced all-cause mortality risk, and caused fewer deaths for coronary heart disease (CHD).
PCSK9 inhibitor resistance may be related to discontinuation of concurrent lipid-lowering therapies after PCSK9 inhibitor initiation.
Occasionally, a limited LDL Cholesterol lowering response may be noted due to PCSK9 inhibitor hypo-responsiveness.
Why This Matters
Considering frequency, mortality, and costs, ACS remains one of the most relevant diseases globally. Over time, the approach for treating ACS has changed.
This review aims to highlight the beneficial effect of early use of PCSK9 inhibitors post-ACS in reducing LDL-C and MACE risk, which is very high in the first year and continues to stay high after the acute event.
Key Highlights
PCSK9 Inhibitors is implied both directly and indirectly in atherosclerotic plaque formation.
It acts directly via the proinflammatory oxidation of LDL Cholesterol and modification of plaque composition for an inflammatory response.
It acts indirectly by affecting lipid metabolism (by modulating LDLR, very LDLR, and LDLR-related protein-1 expression) and platelet aggregation.
Iannuzzo G, Gentile M, Bresciani A, Mallardo V, Di Lorenzo A, Merone P, et al. Inhibitors of protein convertase subtilisin/kexin 9 (PCSK9) and acute coronary syndrome (ACS): The state-of-the-art. J Clin Med. 2021;10(7):1510. doi:10.3390/jcm10071510. PMID:33916362.
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