Association of baseline LDL-C with total and cardiovascular mortality in patients using proprotein convertase subtilisin-kexin type 9 inhibitors: A systematic review and meta-analysis

Safi U. Khan, Haris Riaz, Hammad Rahman, Muhammad U. Khan, Muhammad Shahzeb Khan, Mohamad Alkhouli, Edo Kaluski, Thorsten M. Leucker, Michael J. Blaha

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: The objective of this study was to investigate whether baseline low-density lipoprotein cholesterol (LDL-C) levels influence total and cardiovascular mortality reduction associated with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor therapy. Methods: In this meta-analysis, 9 randomized controlled trials were selected using Medline, Embase, and CENTRAL until November 2018. Analyses were stratified by mean baseline LDL-C (<100 mg/dL and ≥ 100 mg/dL). Stepwise prespecified sensitivity analyses were performed after excluding the SPIRE trials and by regrouping ODYSSEY OUTCOME mortality data according to the baseline LDL-C (< and ≥100 mg/dL). Results: In 83,321 patients, PCSK9 inhibitor therapy was not associated with a reduction in the risk of all-cause mortality (relative risk [RR], 0.94, 95% confidence interval [CI], 0.81–1.09, P =.41). These results remained consistent after excluding the SPIRE trials (RR, 0.89, 95% CI, 0.75–1.05, P =.18). However, the RR varied by baseline LDL-C, with significant RR reduction only in patients with LDL-C ≥ 100 mg/dL (RR, 0.39, 95% CI, 0.20–0.76) (P-interaction =.01). Meta-regression showed RR of 0.97 for all-cause mortality per 1 mg/dL higher baseline LDL-C (95% CI, 0.94–0.99). PCSK9 inhibitor therapy showed no significant effect on cardiovascular mortality, with no effect when excluding the SPIRE trials. However, after regrouping ODYSSEY OUTCOME estimates, there was a significant reduction in cardiovascular mortality restricted to patients with LDL-C ≥ 100 mg/dL (RR, 0.67, 95% CI, 0.51–0.87) (P-interaction =.006). Conclusion: PCSK9 inhibitor therapy on a background statin treatment may reduce the risk of total and cardiovascular mortality in patients with baseline LDL-C ≥ 100 mg/dL. These results support current guidelines reserving PCSK9 inhibitors for high-risk patients with residually high LDL-C.

Original languageEnglish (US)
Pages (from-to)538-549
Number of pages12
JournalJournal of clinical lipidology
Volume13
Issue number4
DOIs
StatePublished - Jul 1 2019

Keywords

  • Meta-analysis
  • Mortality
  • Proprotein convertase subtilisin-kexin type 9 inhibitors

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

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