Cited by 588Lipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular DiseasesParaoxonase enzyme and polymorphisms

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Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease

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The STABILITY Investigators·2014·New England Journal of Medicine

DOI 10.1056/nejmoa1315878

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Abstract

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

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Authors: The STABILITY Investigators
Affiliations: University of Auckland (NZ)
Corresponding author: The STABILITY Investigators
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2014-05
Volume: 370
Issue: 18
Pages: 1702-1711
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1315878
OpenAlex: W1572528121
Cited by: 579
References: 22
Citations by year: 2026: 23 · 2025: 34 · 2024: 33 · 2023: 27 · 2022: 47 · 2021: 38 · 2020: 34 · 2019: 36 · 2018: 48 · 2017: 63 · 2016: 71 · 2015: 85 · 2014: 37
FWCI: 85.88
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Spiral (Imperial College London) (submittedVersion)
UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders: Uppsala Universitet
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords: darapladib, lipoprotein-associated phospholipase A2, stable coronary artery disease, cardiovascular events, myocardial infarction, stroke, cardiovascular mortality, major coronary events, all-cause mortality, atherosclerotic plaque vulnerability, lipid-lowering therapy, unstable angina
MeSH terms: Aged, Benzaldehydes, Biphenyl Compounds, Coronary Artery Disease, Coronary Disease, Diethylamines, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction, Oximes, Pyrimidinones, Sulfides, Treatment Failure, Stroke, Kaplan-Meier Estimate, Phospholipase A2 Inhibitors

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Darapladib for Preventing Ischemic Events in Stable Coronary Heart Disease

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