Impact of early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with acute coronary syndrome: A systematic review meta-analysis

Objective: Scant data is available on the efficacy and safety of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) for early and rapid reduction of low-density lipoprotein cholesterol (LDL-C) within 4-8 weeks of an acute event in patients with acute coronary syndrome (ACS). We undertook this meta-analysis to address this knowledge-gap. Methods: Electronic databases were searched for RCTs involving patients with ACS receiving PCSK9i in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in 1-month LDL-C post ACS. Secondary outcomes were to evaluate alterations in other lipid parameters and adverse events. Results: From initially screened 194 articles, data from 3 studies was analyzed. After 4-weeks therapy, patients receiving PCSK9i had lower LDL-C [MD -0.95 mmol/L (95%CI:-1.51 to -0.40); P = 0.0007; I2 = 96%, total cholesterol (TC) [MD-1.05 mmol/L (95%CI:-1.83 to -0.27); P = 0.009; I2 = 94%] and triglycerides (TG) [MD-0.27 mmol/L (95%CI:-0.44 to -0.10); P = 0.002; I2 = 0%] compared to controls. After 4-8 weeks therapy, patients receiving PCSK9i has lower apolipoprotein B [MD-27.74% (95%CI:-42.59 to -12.89); P = 0.0003; I2 = 89%] as compared to controls. High density lipoprotein cholesterol (HDL-C) [MD 0.05 mmol/L (95%CI:-0.00-0.11); P = 0.05; I2 = 0%], lipoprotein(a) [MD-20.63 mmol/L (95%CI:-41.86 - 0.59); P = 0.06; I2 = 54%] and apolipoprotein A1 [MD 0.02 g/L (95%CI:-0.02-0.07); P = 0.32; I2 = 0%] were comparable between groups. Hospital readmission for ACS was significantly lower in group receiving PCSK9i compared to controls [OR0.25 (95%CI:0.07-0.85); P = 0.03; I2 = 0%]. Occurrence of cardiac death [OR3.75 (95%CI:0.41-34.22); P = 0.24; I2 = 0%], serious adverse events [OR0.71 (95% CI:0.13-3.83); P = 0.69; I2 = 70%] and total adverse events [OR1.01 (95%CI: 0.19-5.30); P = 0.99; I2 = 92%] was comparable between groups. Conclusion: PCSK9i are highly effective in early reduction of LDL-C along with reduction of early hospital readmissions post-ACS. (c) 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).