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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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Association of PCSK9 inhibitors with mortality: insights from a retrospective cohort analysis

Chi-Hsien Huang1,2, Shiow-Ing Wang3,4, Frank S Fan5

  • 1Department of Family Medicine and Community Medicine, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.

European Heart Journal. Cardiovascular Pharmacotherapy
|July 25, 2024
PubMed

Insights

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lowered all-cause mortality and medical utilization compared to statins. This suggests PCSK9 inhibitors are valuable for managing dyslipidaemia, especially in statin-intolerant patients.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Health Services Research

Background:

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events.
  • The comparative impact of PCSK9 inhibitors versus statins on all-cause mortality and medical utilization remains unclear.

Purpose of the Study:

  • To investigate the association of PCSK9 inhibitor use with all-cause mortality and medical utilization compared to statin therapy.
  • To analyze real-world data on PCSK9 inhibitor effectiveness in a large patient cohort.

Main Methods:

  • Retrospective cohort study using the TriNetX database (July 2015–December 2023).
  • Included 79,194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5,437,513 statin users with hyperlipidaemia.
  • Propensity score matching was employed to compare outcomes.

Main Results:

  • PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality (aHR 0.717, 95% CI: 0.673-0.763) compared to statins.
  • Significant reductions were observed in medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation.
  • Findings were consistent across diverse demographics and clinical subgroups, supported by sensitivity analyses.

Conclusions:

  • PCSK9 inhibitors demonstrate a significant benefit in reducing both all-cause mortality and medical utilization compared to statins.
  • These findings highlight the important role of PCSK9 inhibitors in dyslipidaemia management, particularly for patients who are statin-naïve or intolerant.
  • Further research, including randomized controlled trials, is warranted to confirm these results and elucidate underlying mechanisms.
Abstract

Keywords:
All-cause mortalityMedical utilizationPCSK9 inhibitorsStatins

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