Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial

Sabatine, Marc S.; Antman, Elliott M.; Widimský, Petr; Ebrahim, Iftikhar O; Kiss, Róbert Gábor; Saaiman, A; Polášek, Rostislav; Contant, Charles F.; McCabe, Carolyn H.; Braunwald, Eugene

doi:10.1016/s0140-6736(09)61454-9

Cited by 122 publications

(73 citation statements)

References 25 publications

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“…For this study, we pooled individual patient-level clinical and biomarker data from 2 trials of patients with NSTE-ACS (14,15 ). Entry criteria for the Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS (EARLY-ACS) (n ϭ 9492) and Otamixaban for the Treatment of Patients with NSTE-ACS (SEPIA-ACS1-TIMI 42) (n ϭ 3241) trials were similar, with both trials enrolling patients with resting chest pain lasting more than 10 min within 24 h of randomization with ischemic electrocardiographic changes or biomarker increases (creatine kinase MB fraction or troponin above the local laboratory upper limit of the reference interval).…”

Section: Study Population and Endpointsmentioning

confidence: 99%

“…In EARLY-ACS, patients were randomized to early routine glycoprotein IIb/IIIa inhibitor therapy (eptifibatide) before invasive angiography or delayed, provisional use at the time of percutaneous coronary intervention (PCI) (14 ). SEPIA-ACS1-TIMI 42 was a dose-ranging randomized study of otamixaban (an intravenous factor Xa inhibitor) vs heparin plus eptifibatide (15 ). For the purposes of this analysis, we examined the 30-day rates of cardiovascular death or new or recurrent MI (distinct from the qualifying ACS).…”

Section: Study Population and Endpointsmentioning

confidence: 99%

“…For the purposes of this analysis, we examined the 30-day rates of cardiovascular death or new or recurrent MI (distinct from the qualifying ACS). One of 2 independent clinical event committees, blinded to treatment allocation as well as the investigational biomarker results used in this analysis, adjudicated each endpoint according to definitions that we have published previously (14,15 ).…”

Section: Study Population and Endpointsmentioning

confidence: 99%

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Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

et al. 2014

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BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.

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Section: Study Population and Endpointsmentioning

confidence: 99%

Section: Study Population and Endpointsmentioning

confidence: 99%

Section: Study Population and Endpointsmentioning

confidence: 99%

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Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome

et al. 2014

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“…Trials have demonstrated a similar efficacy endpoint when compared to heparins, both given with GP IIB/IIIa inhibitors [32,[70][71][72]] with significant reduction in major bleeding [73]. c. Direct inhibitors of factor Xa such as apixaban, rivaroxaban and otamixaban: while apixaban and rivaroxaban have been used mainly for management of deep vein thrombosis, otamixaban, an investigational anti-factor Xa compound, in intermediate dosages, has been found, in initial studies [74] to offer substantial reduction in major coronary complications such as death and myocardial infarction in patients presenting with NSTEMI, with similar bleeding rate when compared to a combination of UFH and eptifibatide. d. Indirect inhibitors of factor Xa such as fondaparinux:…”

Section: Anti-coagulant Therapymentioning

confidence: 99%

Treatment of NSTEMI (Non-ST Elevation Myocardial Infarction)

Anantharaman

Lim

2013

Curr Emerg Hosp Med Rep

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Non-ST elevation myocardial infarction (NSTEMI) is a recognized diagnostic entity that has an unacceptable mortality rate when it goes unrecognized. Following diagnosis, initial treatment with analgesics, nitrates and anti-platelet agents forms the initial approach. New anti-platelet agents such as ticagrelor and prasugrel need to be clearly understood. Simultaneously, risk stratification for ischaemia and bleeding of each such patient into mild, moderate and severe helps determine the course of further treatment that will be provided to the patient. The major decision is the need for and timing of early coronary angiography to determine the anatomy of the culprit vasculature and the decision for coronary revascularization, either by the percutaneous approach or coronary artery bypass grafting. It is at this stage that the need for and type of anticoagulation will require decision making. Choices include fondaparinux, the heparins, bivalirudin and inhibitors of the coagulation cascade.

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“…117 All patients received aspirin and clopidogrel and 62.7% underwent PCI. Although the rates of the primary effi cacy outcome, a composite of death, MI, urgent revascularization, or bailout glycoprotein IIb/IIIa use at 7 days, were not signifi cantly different across the fi ve doses of otamixaban or compared with heparin plus eptifi batide, rates were numerically lowest with the two intermediate doses of otamixaban.…”

Section: Factor Xa Inhibitorsmentioning

confidence: 99%