Clinical InvestigationAcute Ischemic Heart DiseaseFondaparinux compared to enoxaparin in patients with acute coronary syndromes without ST-segment elevation: Outcomes and treatment effect across different levels of risk
Section snippets
Methods
OASIS-5 was a randomized double-blind, double-dummy trial in which fondaparinux (GlaxoSmithKline, King of Prussia, PA) 2.5 mg subcutaneous. Daily was compared with enoxaparin (Sanofi-Aventis, Paris, France) 1 mg/kg subcutaneous twice daily in patients with unstable angina and non–ST-elevation MI. In patients whose creatinine clearance was <30 mL/min, the enoxaparin dosage was reduced to 1 mg/kg daily. The design rationale and results of the study have been previously reported in detail.8, 14
Study patients
The demographic and clinical characteristics of the 20,078 patients enrolled in OASIS-5 study have been published previously.8 The mean age of the patients was 66.6 years and time from onset of pain to randomization was 12.7 hours. Almost 80% of the patients had an abnormal electrocardiogram on presentation. Coronary angiography was performed in 63.3% of patients, and 34.3% underwent percutaneous coronary intervention during the index hospitalization. Table I provides details of the components
Discussion
In our population of >20,000 patients, we have confirmed previous observations that the GRACE score is an excellent tool for predicting in hospital and 6 month mortality (Figure 1).
The current analysis demonstrates that at any level of risk as assessed by the GRACE score, the balance between antithrombotic efficacy and bleeding risk is favorable for fondaparinux. The benefits of fondaparinux were similar at all levels of risk (Figure 2). The risk of bleeding was reduced by about 50% with
Disclosures
The OASIS-5 (Organization to Assess Strategies in Ischemic Syndromes-5) study was supported by Sanofi-Aventis (Paris, France), Organon (Kenilworth, NJ), and GlaxoSmithKline (King of Prussia, PA). There was no separate funding for the current analysis.
Dr Joyner reports receiving a research grant from Sanofi-Aventis. Dr Peters reports speaker bureau and honoraria with several pharmaceutical companies, and advisory boards with Sanofi-Aventis, Astra Zeneca (Wilmington, DE), and GlaxoSmithKline. Dr
Acknowledgements
We are indebted to Marcie Katz and Marivel Magsino for their secretarial assistance.
References (19)
- et al.
Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomized clinical trials
Lancet
(2002) - et al.
Guidelines for the diagnosis and treatment of non–ST-elevation acute coronary syndromes
Eur Heart J
(2007) - et al.
ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction
Circulation
(2007) Collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
BMJ
(2002)- et al.
Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation
N Engl J Med
(2001) - et al.
Routine vs. selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials
JAMA
(2005) - et al.
Adverse impact of bleeding on prognosis in patients with acute coronary syndromes
Circulation
(2006) - et al.
Comparison of fondaparinux and enoxaparin in acute coronary syndromes
N Engl J Med
(2006) - et al.
The TIMI risk score for unstable angina/non–ST elevation MI: a method for prognostication and therapeutic decision-making
JAMA
(2000)
Cited by (30)
External Validation of the DAPT Score in a Nationwide Population
2018, Journal of the American College of CardiologyCan't Bare It any Longer
2016, JACC: Cardiovascular InterventionsESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation
2012, Revista Espanola de CardiologiaPart 9: Acute coronary syndromes: 2010 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations
2010, ResuscitationCitation Excerpt :One RCT (LOE 1),350 three nonrandomised control studies (LOE 2),351–353 and two additional studies (LOE 5)354,355 demonstrated improved combined end points (death, MI, revascularization) without increased bleeding when fondaparinux, compared with UFH, was administered in-hospital in patients with AMI. Three studies did not demonstrate a difference in outcomes for fondaparinux compared with UFH when given in hospital (LOE 2356,357; LOE 5358). One RCT indicated fondaparinux may lead to excess catheter thrombosis when used as part of an invasive approach without the use of adjunctive medications (LOE 1).350
Temporal trend of in-hospital major bleeding among patients with non ST-elevation acute coronary syndromes
2010, American Heart Journal
Clinical trial registration: ClinicalTrials.gov no. NCT00139815.
Dr. Debabrata Mukherjee served as guest editor for this manuscript.