Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction: The OASIS-6 Randomized Trial

Yusuf, Salim; Mehta,; Chrolavicius, Susan; Afzal, Rizwan; Pogue, Janice; Granger, Claire; Budaj, Andrzej; Rj, Peters; Jp, Bassand; Wallentin, Lars; Joyner, Campbell; Fox, Keith A.A.

doi:10.1001/jama.295.13.joc60038

Cited by 762 publications

(70 citation statements)

References 13 publications

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“…Furthermore, the place of fondaparinux in the setting of PCI for patients with non-ST-segment-elevation acute coronary syndromes remains poorly defined. 16 The drug was found to be harmful in patients with ST-segment-elevation myocardial infarction 17 and current guidelines do not recommend its use in the setting of primary PCI (class III recommendation). 5 The use of glycoprotein IIb/IIIa inhibitors as bailout strategy (apparently included in the subgroup analysis of patients without planned use of these agents) may further distort the ability of ACT to predict especially ischemic complications because in general glycoprotein IIb/IIIa inhibitors are used as a bailout strategy in patients considered at imminent risk of complications (mostly ischemic complications).…”

Section: See Article By Ducrocq Et Almentioning

confidence: 99%

Activated Clotting Time During Percutaneous Coronary Intervention

Ndrepepa

Kastrati

2015

Circ: Cardiovascular Interventions

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U nfractionated heparin (UFH) has been used clinically as an anticoagulant since 1935.1,2 Thirty-one years later, the activated clotting time (ACT) was developed as a test for the diagnosis and management of patients with inherited coagulation disorders.3 Later, the ACT test was extensively used to monitor UFH therapy in patients undergoing cardiopulmonary bypass surgery or percutaneous coronary interventions (PCI). Although ACT is often seen as a crude and imprecise test that does not correlate with other coagulation tests, 4 it remains the most commonly used point-of-care test to monitor UFH during PCI procedures. Guidelines recommend target ACT values within 200 to 250 s with planned use of glycoprotein IIb/IIIa inhibitors and 250 to 300 s (Hemotech device) or 300 to 350 s (Hemochron device) without planned use of glycoprotein IIb/IIIa inhibitors for the guidance of UFH therapy during primary PCI procedures. 5 The reference range for the target ACT is mostly empiric 6 or based on small-scale studies. 7-9 With regard to the association between ACT values and thrombotic or bleeding complications after PCI, studies remain markedly divided. A meta-analysis of 6 randomized trials of patients undergoing PCI by Chew et al 10 showed that the risk of ischemic events reduced progressively with increasing ACT levels. The lowest rate of bleeding (8.6%) was observed in the ACT range between 325 and 350 s and it increased to 12.4% at ACT 350 to 375 s. However, this study included a heterogeneous population of the patients with a broad range of indications for PCI and only a small minority of patients received coronary stents or antithrombotic therapy (ticlopidine or clopidogrel). As a consequence, the study does not reflect the current practice of PCI. Another meta-analysis of 4 randomized trials, more contemporary in terms of the use of coronary stents or antiplatelet therapy by Brener et al 11 and a post hoc analysis from the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) trial 12 came to opposite conclusions. Both studies did not find an association between ACT and ischemic complications in the poststenting period. A modest association between increasing ACT and bleeding events was observed either mainly driven by minor bleeding 11 or enhanced by eptifibatide use. 12 Thus, despite 80 years of clinical experience and almost universal acceptance of anticoagulation with UFH as a standard of care during PCI to prevent thrombotic events, the adequate UFH dosing or the relevance of monitoring of therapy with UFH by ACT remains debatable. See Article by Ducrocq et alIn this issue of Circulation: Cardiovascular Interventions, Ducrocq et al 13 assessed the relationship between the UFH dose and the peak ACT and whether there is an association between peak ACT value and thrombotic or bleeding outcomes in patients with non-ST-segment-elevation acute coronary syndromes treated by PCI. The study represents a post hoc analysis of the Fondaparinux With Unfractionated Heparin During Revasculariz...

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Section: See Article By Ducrocq Et Almentioning

confidence: 99%

Activated Clotting Time During Percutaneous Coronary Intervention

Ndrepepa

Kastrati

2015

Circ: Cardiovascular Interventions

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“…Early in the course of ACS, the short-term use of parenteral anticoagulants, such as unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux and bivaluridin, have reduced the incidence of thrombotic events [18,19,20,21,22,23,24]. A meta-analysis of randomized trials using UFH and ASA in patients with unstable angina pectoris showed a 33% reduction in myocardial infarction (MI) and cardiovascular mortality compared to placebo [20].…”

Section: Current Anticoagulation Therapymentioning

confidence: 99%

Role of Oral Factor Xa Inhibitors after Acute Coronary Syndrome

et al. 2014

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Despite an early invasive strategy and the use of dual antiplatelet therapy, patients with acute coronary syndrome (ACS) continue to be at substantial risk for recurrent ischemic events. It is believed that this risk is, at least in part, due to an intrinsic coagulation pathway that remains activated for a prolonged period after ACS. Earlier studies using warfarin showed a reduction in ischemic events, but the overall benefits were offset by increased bleeding complications. Recently, there has been increased interest in the potential role of new oral anticoagulants, some of which target factor Xa, after ACS. Factor Xa is important for the coagulation pathway and also plays a role in cellular proliferation and inflammation. It may thus be an attractive target for therapeutic intervention in ACS. Recently, various oral factor Xa inhibitors have been studied as potential treatment options for ACS. This review will focus on currently available data to evaluate the possible role of factor Xa inhibitors in the management of patients with ACS.

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“…Free fatty acids are normally the primary fuel source for the heart but are toxic to the 17 myocardium in the ischemic setting causing sarcolemmal and mitochondrial membrane disruption [15]. evidence in favour of GIK (total 525 patients) [21,22], seven showed no difference (25,496 patients) [23][24][25][26][27][28][29], and 7 one showed increased harm (954 patients) [30].…”

mentioning

confidence: 99%

“…However, in 5 studies the rates were not mentioned at all 7 [28,26,27,29,21]. Some studies recorded symptomatic hypoglycaemia only (not biochemical) and this would 8 significantly underestimate true biochemical hypoglycemia [22,25].…”

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confidence: 99%

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Insulin in Acute Coronary Syndrome: a Narrative Review with Contemporary Perspectives

Nam

Byrne

Kaski

et al. 2016

Cardiovasc Drugs Ther

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1The role of insulin in the treatment of acute coronary syndrome (ACS) has been widely studied over the past 2 100 years. The current indication for its use in this context is the treatment of hyperglycemia, irrespective of 3 diabetes, which is associated with adverse outcome. Initial theories proposed that glucose was beneficial in 4 the context of myocardial ischemia and insulin was required to enable glucose cell uptake. However, studies 5 testing this hypothesis with routine insulin administration during ACS have produced disappointing results and 6 research interest has therefore declined. We propose that the less well known but important vasodilator effect 7 of insulin has been overlooked by some of these studies and warrants further consideration. Previous reports 8 have shown that hyperinsulinemic euglycaemia improves myocardial blood flow reserve. With this in mind, this 9 review considers the role of insulin in the context of ACS from the perspective of a vasodilator rather than a 10 metabolic modulator. We discuss the importance of time to treatment, dosage of insulin administered, 11problems with hypoglycaemia and insulin resistance, and how they may have affected the outcomes of the 12 major trials. Finally, we propose new study designs that allow determination of the optimal vasodilator 13 conditions for the use of insulin as adjunctive pharmacotherapy during myocardial ischaemia.

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Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction: The OASIS-6 Randomized Trial

Abstract: ClinicalTrials.gov Identifier NCT00064428.

Cited by 762 publications

References 13 publications

Activated Clotting Time During Percutaneous Coronary Intervention

Activated Clotting Time During Percutaneous Coronary Intervention

Role of Oral Factor Xa Inhibitors after Acute Coronary Syndrome

Insulin in Acute Coronary Syndrome: a Narrative Review with Contemporary Perspectives

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