Abstract:
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In patients with stable atherosclerotic cardiovascular disease, PCSK9 inhibitors (PCSK9i) have
shown a 50-60% reduction in LDL-C from baseline, added to high-intensity statin therapy.
However, less is known about the impact of PCSK9i in the setting of an acute coronary
syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing
PCSK9i with placebo in the setting of ACS, added to guideline directed high-intensity or
maximally tolerated statin therapy. We included randomized controlled trials (RCTs) with
initiation of PCSK9i or placebo within 1 week of presentation or percutaneous coronary
intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study
followed Cochrane and PRISMA recommendations. Six RCTs were included, totalizing 996
patients of whom 503 (50.5%) received PCSK9i. Mean follow-up ranged from 4 to 52 weeks.
LDL-C (MD -44 mg/dL; CI -54.3 to -33.8; p<0.001) and Lp(a) levels (MD -24.0 nmol/L; CI -
43.0 to -4.9; p=0.01) were significantly lower at follow-up with PCSK9i. Similarly, total
cholesterol (MD -49.2 mg/dL; CI -59 to -39.3), triglycerides (MD -19 mg/dL; CI -29.9 to -8.2)
and Apo B (MD -33.3 mg/dL; CI -44.4 to -22.1) were significantly reduced with PCSK9i. In
conclusion, in patients with ACS, early initiation of PCSK9i, added to statin, significantly
reduces LDL-C and Lp(a) as compared with placebo. Whether the differences in these
atherogenic lipoproteins translate into a reduction in clinical endpoints is yet to b e determined. |