Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes
Open accessAbstract
BACKGROUND: The combined use of anticoagulants, antiplatelet agents, and invasive coronary procedures reduces ischemic coronary events but also increases bleeding in patients with acute coronary syndromes. We therefore assessed whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding. METHODS: We randomly assigned 20,078 patients with acute coronary syndromes to receive either fondaparinux (2.5 mg daily) or enoxaparin (1 mg per kilogram of body weight twice daily) for a mean of six days and evaluated death, myocardial infarction, or refractory ischemia at nine days (the primary outcome); major bleeding; and their combination. Patients were followed for up to six months. RESULTS: The number of patients with primary-outcome events was similar in the two groups (579 with fondaparinux [5.8 percent] vs. 573 with enoxaparin [5.7 percent]; hazard ratio in the fondaparinux group, 1.01; 95 percent confidence interval, 0.90 to 1.13), satisfying the noninferiority criteria. The number of events meeting this combined outcome showed a nonsignificant trend toward a lower value in the fondaparinux group at 30 days (805 vs. 864, P=0.13) and at the end of the study (1222 vs. 1308, P=0.06). The rate of major bleeding at nine days was markedly lower with fondaparinux than with enoxaparin (217 events [2.2 percent] vs. 412 events [4.1 percent]; hazard ratio, 0.52; P<0.001). The composite of the primary outcome and major bleeding at nine days favored fondaparinux (737 events [7.3 percent] vs. 905 events [9.0 percent]; hazard ratio, 0.81; P<0.001). Fondaparinux was associated with a significantly reduced number of deaths at 30 days (295 vs. 352, P=0.02) and at 180 days (574 vs. 638, P=0.05). CONCLUSIONS: Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity. (ClinicalTrials.gov number, NCT00139815.).
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In the fondoparinux vs. enoxaparin trial, equivalence was defined as a value of the RR less than 1.185 or the risk of the outcome for the fondoparinux group at most 18.5% larger than the risk of the outcome for the enoxaparin group.
“In the fondoparinux vs. enoxaparin trial 3 , equivalence was defined as a value of the RR less than 1.185 or the risk of the outcome for the fondoparinux group at most 18.5% larger than the risk of the outcome for the enoxaparin group.”
From Understanding Equivalence and Noninferiority Testing (2011) · cites this paper as [3]
The Statistical Analysis section specifies a noninferiority margin of 1.185, and Efficacy says the trial met it because the upper 95% confidence limit was below that boundary. The claim gets the numerical margin right but calls it equivalence and describes it as a risk-ratio cutoff; the paper applies the boundary to a hazard ratio’s upper confidence limit, not simply to the observed risk ratio. (LLM, conf=0.92)
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- Authors
- The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators
- Corresponding author
- The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-04-06
- Volume
- 354
- Issue
- 14
- Pages
- 1464-1476
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2095901832
- Cited by
- 1,228
- References
- 1
- Citations by year
- 2026: 17 · 2025: 25 · 2024: 19 · 2023: 18 · 2022: 28 · 2021: 27 · 2020: 24 · 2019: 29 · 2018: 43 · 2017: 38 · 2016: 37 · 2015: 60 · 2014: 67 · 2013: 64 · 2012: 101
- FWCI
- 87.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Own your potential (DEAKIN) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- enoxaparin, acute coronary syndrome, anticoagulation, major bleeding, non-inferiority, myocardial infarction, refractory ischemia, mortality, direct oral anticoagulants, heparinoids, antiplatelet therapy
- MeSH terms
- Fondaparinux, Aged, Angina, Unstable, Anticoagulants, Female, Hemorrhage, Humans, Male, Middle Aged, Myocardial Infarction, Polysaccharides, Recurrence, Angioplasty, Balloon, Coronary, Survival Analysis, Treatment Outcome, Enoxaparin, Stroke
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