Early administration of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis

BMC Cardiovasc Disord. 2024 Jul 30;24(1):395. doi: 10.1186/s12872-024-04057-w.

Abstract

Background: High-intensity statin therapy is currently recommended initial guideline therapy in ACS treatment. However, only a minority of patients are achieving LDL-C attainment goal at 6 months. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are on recommended guideline therapy post-ACS if LDL-C goal attainment is not achieved after high-intensity statin (4-6 weeks) and after the addition of ezetimibe if guideline goal attainment is not achieved after an additional 4-6 weeks. Thus, it has been recommended that PCSK9 inhibitors be considered earlier post-ACS. However, the efficacy of early PCSK9 inhibitors initiation in ACS patients remains uncertain.

Methods: This systematic review and meta-analysis was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and observational studies involving ACS patients who received PCSK9 inhibitors within 48 h of hospitalization were included. Common and random effects models were used to evaluate the pooled effect of early PCSK9 inhibitor administration. Nine RCTs and three cohort studies were included.

Results: Early PCSK9 inhibitor administration reduced the incidence of MI, ACS hospitalization, and revascularization at 6-18 months post-ACS. Although there was a drift towards reduced stroke, all-cause mortality, and cardiovascular death, no statistically significant reduction was observed. Additionally, PCSK9 inhibitors significantly enhanced lipid control at 4-12 weeks after index hospitalization.

Conclusion: Early PCSK9 inhibitors initiation in ACS patients reduces MACE and improves lipid profiles. While the results propose promising benefits in terms of stroke and mortality, further research with longer follow-up is required for more decisive evidence.

Keywords: Acute coronary syndrome; Lipid lowering; MACE; PCSK9 inhibitors.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Acute Coronary Syndrome* / blood
  • Acute Coronary Syndrome* / diagnosis
  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / mortality
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / therapeutic use
  • Biomarkers* / blood
  • Cholesterol, LDL / blood
  • Drug Administration Schedule
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / drug therapy
  • Dyslipidemias / mortality
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / mortality
  • Myocardial Revascularization
  • Observational Studies as Topic
  • PCSK9 Inhibitors*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • PCSK9 Inhibitors
  • Serine Proteinase Inhibitors