Clinical benefit and practical use of fondaparinux in the invasive management of patients with acute coronary syndromes
Interventional Cardiology, Hamilton Health Sciences, General Division, 237 Barton Street East, Hamilton, Ontario, Canada L6K 1B8
* Corresponding author. Tel: +1 905 521 2631; fax: +1 905 527 4463. E-mail address: smehta{at}mcmaster.ca
 |
Abstract |
|---|
 Top Abstract IntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
In patients with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS), an invasive management strategy has been found to be superior to a conservative strategy. In the real world,
50% of patients treated with an invasive strategy require a percutaneous coronary intervention (PCI) procedure, whereas the remaining 40–50% are treated medically and a small proportion (<10%) undergo coronary artery bypass graft surgery. Therefore, anti-thrombotic drugs need to be both safe and effective when started early in a broad range of patients with ACS, regardless of ultimate revascularization status. Fondaparinux is the first selective inhibitor of factor Xa approved for use across the whole spectrum of patients with ACS. In patients with NSTE-ACS in the OASIS-5 study, upstream treatment with fondaparinux was found to have superior net clinical benefit compared with enoxaparin in patients undergoing PCI. Fondaparinux reduced death, myocardial infarction, stroke, or major bleeding by 22% compared with enoxaparin (P = 0.004). Even in those undergoing early PCI (i.e. within the first 24 h), there was a 24% relative risk reduction in favour of fondaparinux (P = 0.035). The main benefit was a large 54% reduction in major bleeding (P < 0.001), which was achieved with near identical rates of ischaemic events (6.3 vs. 6.2%). Catheter thrombus occurred with very low incidence in both the fondaparinux and the enoxaparin groups and was virtually eliminated in both groups with adjunctive unfractionated heparin (UFH) administered in the catheterization laboratory just prior to PCI. In the fondaparinux group, the mean dose of UFH was about 50 U/kg. On the basis of these data and the overall results of the OASIS-5 trial, the experts of the American College of Cardiology/American Heart Association and of the European Society of Cardiology gave fondaparinux a class I recommendation for use in patients with NSTE-ACS undergoing invasive strategy. In practice, fondaparinux is easy to use (fixed dose of 2.5 mg once daily for all patients) and is associated with improved patient outcomes, including those patients managed with an invasive strategy.
Key Words: Acute coronary syndromes • Anticoagulant • Fondaparinux • Low-molecular-weight heparins • Percutaneous coronary intervention • Unfractionated heparin
|
Introduction |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
Anticoagulation is a standard of care for the management of all patients with acute coronary syndromes (ACS), including those managed with an invasive strategy and those managed with a conservative strategy.1,2 In patients with high-risk non-ST-segment elevation ACS (NSTE-ACS), an invasive management strategy has been found to be superior to a conservative strategy.3,4 In the real world, about half of all the patients with NSTE-ACS managed with an invasive strategy will receive a percutaneous coronary intervention (PCI) procedure.5,6 When considering those also treated with an initial conservative strategy (e.g. patients with advanced age or co-morbidities, patient preference), the true rate of PCI in the real world is closer to about 30%. Since it is not known at the time of patient first contact whether a given patient referred for early angiography will receive a PCI or not, anti-thrombotic strategies must be both safe and effective in a broad range of patients.
Unfractionated heparin (UFH) has been the traditional anticoagulant of choice in patients with NSTE-ACS, but its administration requires an intravenous infusion, it may cause heparin-induced thrombocytopenia, and its anticoagulant effect shows a large intra- and inter-individual variability, necessitating regular monitoring of the activated partial thromboplastin time (aPTT). Thus, although it is useful in the catheterization laboratory because it can be given as a single bolus, monitored easily using the activated clotting time (ACT) and reversed if necessary using protamine sulphate, it is not an ideal agent for upstream therapy. Enoxaparin was shown to be superior to UFH in patients undergoing mainly a conservative strategy,7,8 but in patients treated with an invasive strategy, it was no better than UFH and resulted in higher rates of severe bleeding complications in the SYNERGY trial.9,10 Even in those patients who did not switch therapies, in a recent meta-analysis by Petersen et al.,11 enoxaparin was still associated with higher bleeding rates than UFH. Further, there was a significant hazard to using enoxaparin alone in those undergoing early PCI in the SYNERGY trial, making this a sub-optimal agent in this setting.12
Fondaparinux is the first selective inhibitor of factor Xa approved for use across the whole spectrum of patients with ACS.13 In the OASIS-5 trial, fondaparinux was found to be non-inferior to enoxaparin early, but reduced mortality and ischaemic events relative to enoxaparin at 30 days and 6 months.14 It was also substantially safer, with a reduction in major bleeding of about one-half. The overwhelming majority of patients (>14 000) in the OASIS-5 trial were treated with an invasive strategy and about half of these underwent PCI. In this article, we review the data for fondaparinux in patients undergoing an invasive strategy15 and provide practical advice on how to incorporate fondaparinux into routine clinical practice.
|
Results in patients undergoing percutaneous coronary intervention: superior net benefit of fondaparinux |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
Out of 20 078 patients enrolled in OASIS-5, 14 206 patients underwent heart catheterization and 12 715 during the study drug administration period; this procedure was performed in 8919 patients within the first 72 h after randomization, respectively. A total of 6238 patients underwent PCI during the study drug administration period; the procedure was performed within 24 h after randomization in 2834 patients. These data closely reflect current European practice5 (Figure 1).
|
The baseline characteristics were well matched between the two randomized treatment groups (Table 1). Overall, these patients represented an intermediate to a high-risk population; they exhibited high-risk features indicating the need for an early invasive strategy according to the European Society of Cardiology (ESC) guidelines1 (Figure 2).
|
|
Subcutaneous fondaparinux and enoxaparin were given for a mean (±SD) of 2.4 (1.8) days and 2.6 (1.8) prior to PCI, respectively. The median duration of therapy in patients undergoing PCI was 2.5 days. The study drug was stopped either because of clinical stabilization, a revascularization procedure or discharge from hospital. Overall,
99% of patients received aspirin and 92% a thienopyridine (Table 2).
|
At Day 9, death, myocardial infarction, or stroke in patients undergoing PCI occurred with a similar frequency in the fondaparinux and the enoxaparin group (Table 3). Taken individually, the rate of each of these outcomes was also similar in the two groups. In contrast, major bleeding was reduced by 54% (P < 0.001) in fondaparinux-treated patients. There was a similarly large reduction in the rate of minor and total bleeding with fondaparinux. Overall, the net clinical composite of death, myocardial infarction, stroke, or major bleeding was significantly (P = 0.004) lower in the fondaparinux group than in the enoxaparin group.
|
Whereas the restarting of the study drug after PCI did not increase the rate of major bleeding, fondaparinux was superior to enoxaparin in reducing major bleeding irrespective of whether the study drug was restarted [1.9 vs. 4.4%; hazard ratio (95% confidence interval): 0.42 (0.29–0.60); P < 0.001] or not restarted [3.7 vs. 6.6%; hazard ratio (95% confidence interval): 0.55 (0.35–0.84); P < 0.001] after the procedure.
The bleeding reduction observed in patients treated with fondaparinux was consistent irrespective of age: the hazard ratio (95% confidence interval) was 0.49 (0.37–0.66) (P < 0.001) and 0.58 (0.34–0.99) (P = 0.047) in favour of fondaparinux in patients 
65 years and <65 years, respectively. Fondaparinux also reduced major bleeding compared with enoxaparin irrespective of GPIIb/IIIa inhibitors or thienopyridine use. The trans-radial approach was associated with fewer major bleeding complications than the trans-femoral approach (1.6 vs. 3.5%, P < 0.003), but fondaparinux markedly reduced major bleeding when compared with enoxaparin regardless of the arterial vascular access (Figure 3).16
|
Furthermore, the net clinical benefit in favour of fondaparinux was maintained at Days 30 and 180, highlighting the clinical superiority of fondaparinux over enoxaparin in PCI patients over the long term.
|
Fondaparinux in very early percutaneous coronary intervention |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
Consistent results were obtained in the subgroup of patients in whom PCI was performed within 24 h after randomization (Table 3). At Day 9, death, myocardial infarction or stroke occurred with a similar frequency in the fondaparinux and the enoxaparin group. However, there was a substantial reduction (52%, P < 0.001) in major bleeding in fondaparinux-treated patients. Overall, the net clinical composite of death, myocardial infarction, stroke, or major bleeding was significantly (P = 0.035) lower in the fondaparinux group than in the enoxaparin group.
|
Rapid emergence of bleeding benefit with fondaparinux |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
The safety benefit of fondaparinux in terms of bleeding risk appeared as early as the day of randomization (i.e. within hours of the administration of the first dose of study drug), indicating that, even with very short durations of therapy, fondaparinux was safer in terms of bleeding risk than enoxaparin (Table 4). On subsequent days, the occurrence of major bleeding remained substantially lower with fondaparinux compared with enoxaparin. These results support the administration of fondaparinux in patients with NSTE-ACS who are discharged early from hospital.
|
|
Minimization of catheter thrombus risk with unfractionated heparin as adjunct |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
In the initial protocol, patients randomized to fondaparinux underwent PCI without adjunct UFH. In contrast, in patients randomized to enoxaparin, no additional study drug was given if PCI was performed within 6 h of the last study drug injection. When the interval was more than 6 h, UFH was used in the enoxaparin arm. This strategy was used since enoxaparin is not approved for use in PCI.17 Moreover, neither the ESC nor the American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend its use in PCI.1,2 So far, no anticoagulant has been demonstrated to be more effective than UFH for anticoagulation during PCI. Thus, in enoxaparin patients recruited in OASIS-5, the additional dose of UFH was 100 U/kg when no GPIIb/IIIa inhibitor was used and 65 U/kg when a GPIIb/IIIa inhibitor was administered. Of note, the addition of UFH to the enoxaparin group 6 h after the last subcutaneous enoxaparin administration lowered the rate of abrupt/threatened vessel closure compared with those undergoing PCI with enoxaparin alone (4.3% with UFH+enoxaparin vs. 6.2% with enoxaparin alone, P = 0.026). Importantly, the use of UFH at least 6 h after the last subcutaneous enoxaparin injection did not increase the risk of major bleeding in the enoxaparin group (Figure 4).
|
During the trial, catheter thrombosis was reported to occur in a small number of patients. To reduce this event, the Operations Committee (without any knowledge of the number of catheter thromboses by randomized group) reminded the centres that they were allowed to give open-label UFH prior to PCI in addition to protocol-mandated study drug. Moreover, to record this issue in a more systematic way, the case report forms were amended to capture all cases of catheter thrombus and whether open-label UFH was given in the catheterization laboratory prior to PCI. These data were routinely collected in the final 1758 patients undergoing PCI. For the first time, information on the occurrence of catheter thrombosis was systematically collected in a randomized trial.
Overall, catheter thrombosis occurred very rarely in both groups (but significantly more with fondaparinux) before the implementation of the amendment recommending the open-label use of UFH (Table 5). Of note, previous studies also showed that catheter thromboses may occur in enoxaparin-treated patients.18–20 In the fondaparinux group, the occurrence of this event was virtually eliminated after the amendment with the use of open-label UFH at an average dose of 47 U/kg. Catheter thrombus occurred in 10 fondaparinux-treated patients following the protocol amendment; nine events occurred when no UFH was given prior to PCI and the remaining case occurred in a patient who received a very low dose of open-label UFH (570 U or 5.0 U/kg). Importantly, the addition of open-label UFH did not increase the bleeding rate in the fondaparinux group (1.3% with open-label UFH vs. 3.3% with no open-label UFH) and did not influence the safety benefit of fondaparinux over enoxaparin.
|
Other data showed that whether examining the incidence of local PCI complications + major adverse cardiac events (MACE), or of local PCI complications + major bleeding, there was a consistent net clinical benefit in favour of fondaparinux compared with enoxaparin in PCI patients.
The data of OASIS-6 trial in patients with ST-elevation acute myocardial infarction (STEMI) confirmed the fact that adding UFH to fondaparinux patients undergoing PCI is effective for preventing catheter thrombosis and safe in terms of bleeding risk.21 A total of 250 fondaparinux patients (corresponding to targeted patients in the current European labelling of fondaparinux) and 239 control patients (receiving UFH or placebo upstream PCI) underwent a PCI other than primary PCI (including rescue PCI, routine PCI and PCI for recurrent ischaemia); all of them received UFH as recommended prior to the procedure and no catheter thrombosis was reported in either group. The respective rates of death/myocardial infarction/stroke were 14.3 and 16.0%, whereas the rates of major bleeding were 2.4 and 3.3%. These results are therefore very consistent with the OASIS-5 data in PCI patients and corroborate the statement that it is reasonable to recommend the intravenous use of UFH during PCI at a dose between 50 and 100 U/kg in fondaparinux patients in order to minimize the risk of catheter thrombus without impairing the clinical benefit of the drug.
|
Integrating fondaparinux into daily practice in patients managed with an invasive strategy |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
In the latest guidelines established by the ACC/AHA and the ESC, fondaparinux was recommended with a class I recommendation in patients undergoing invasive strategy.1,2
Figures 5 and 6 show a flow diagram on the recommended use of fondaparinux in patients with NSTE-ACS, with invasive strategy in higher-risk patients and conservative strategy in low-risk patients.
|
|
In patients requiring primary PCI for STEMI or urgent PCI within minutes to hours (e.g. shock), UFH is recommended for initial treatment. All other NSTE-ACS patients, for whom the decision to undergo conservative or invasive management is pending, should receive initial treatment by fondaparinux 2.5 mg subcutaneously.1,2
Percutaneous coronary intervention procedures
If a patient treated with fondaparinux is scheduled to undergo PCI, the transition to the catheterization laboratory is simple in practice. In situations where a patient has on-going chest pain and haemodynamic instability, there is no need to delay the procedure—in this scenario of early PCI, patients should proceed to the catheterization laboratory and UFH should be administered intravenously in the catheterization laboratory at a standard dose (50–100 U/kg). If patients have stabilized initially, catheterization can be delayed and if PCI is needed, standard UFH should be administered as a bolus prior to the procedure at a dose of 50–100 U/kg. The dose of 50 U/kg of UFH may be preferred in fondaparinux patients who were co-administered GPIIb/IIIa antagonists. However, it must be underlined that no change to current practice is needed concerning the use and dose of GPIIb/IIIa inhibitors. Thus, for interventional cardiologists accustomed to using UFH for the PCI procedure, adding UFH on top of fondaparinux for the PCI procedure does not represent a significant change from their routine practice. Bivalirudin may be an option instead of UFH and a GPIIb/IIIa antagonist in patients treated upstream with fondaparinux based on the low bleeding risk with both agents, but no data have been published using this novel combination (trials are on-going).
Sheath removal procedures
If a closure device is used, or in the case of radial access, sheath removal should be immediate; if no closure device is used, sheath removal should be performed at least 6 h after last fondaparinux subcutaneous dose. As with other anticoagulants, the administration of fondaparinux may be stopped within 24 h of the invasive procedure, but this may be left to the physician's discretion. If restarted after the PCI, the next fondaparinux injection should be performed 2 h after sheath removal, while leaving 24 h between two fondaparinux injections. If coronary artery bypass graft surgery was selected after diagnostic angiography, discontinuation of fondaparinux 24 h before the procedure is recommended.
|
Conclusion |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
Fondaparinux is the first selective inhibitor of factor Xa approved for use in patients with NSTE-ACS (excluding patients requiring PCI within two hours after symptom onset) or STEMI (treated with thrombolytics or no reperfusion) at a dose of 2.5 mg once daily. The clinical benefit of fondaparinux was demonstrated in patients with NSTE-ACS undergoing early PCI and in patients with STEMI undergoing non primary PCI. In a combined analysis of patients undergoing PCI in the OASIS-5 and OASIS-6 studies, fondaparinux was similar to UFH or enoxaparin in reducing death, myocardial infarction, or stroke (8.0 vs. 8.0%), but reduced major bleeding (2.9 vs. 5.5%; hazard ratio: 0.52; P < 0.0001), resulting in a superior net clinical benefit as assessed by death, myocardial infarction, stroke, or major bleeding (9.0 vs. 11.8%; hazard ratio: 0.75; P = 0.01).22 If a PCI is performed in patients treated upstream with fondaparinux, it is recommended that adjunctive intravenous UFH be given at a dose of
50–100 U/kg to minimize the risk of catheter thrombus. In practice, fondaparinux is easy to use (2.5 mg once daily for all patients) and is a simplification vs. UFH or enoxaparin treatments as no dose adjustments are necessary. Because dose adjustments are not needed, it may limit dosing errors that have been reported with other anti-thrombotic drugs which may increase bleeding or death.23 Fondaparinux is a new standard of anticoagulation that should bring significant reductions in bleeding and improve the overall prognosis of patients with ACS who are managed both with an invasive and a non-invasive approach.
Conflict of interest: Consultant and/or research grants and/or honoraria from GlaxoSmithKline, Sanofi-Aventis, Boston Scientific, Abbott Vascular, Bristol Myers Squibb, Eli Lilly, Oryx, Astrazeneca.
|
References |
|---|
|
TopAbstractIntroductionResults in patients undergoing...Fondaparinux in very early...Rapid emergence of bleeding...Minimization of catheter...Integrating fondaparinux into...ConclusionReferences |
|---|
- Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernández-Avilés F, Fox KA, Hasdai D, Ohman EM, Wallentin L, Wijns W ESC Committee for Practice Guidelines (CPG), Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Kristensen SD, Widimsky P, McGregor K, Sechtem U, Tendera M, Hellemans I, Gomez JL, Silber S, Funck-Brentano C, Kristensen SD, Andreotti F, Benzer W, Bertrand M, Betriu A, De Caterina R, DeSutter J, Falk V, Ortiz AF, Gitt A, Hasin Y, Huber K, Kornowski R, Lopez-Sendon J, Morais J, Nordrehaug JE, Silber S, Steg PG, Thygesen K, Tubaro M, Turpie AG, Verheugt F, Windecker S, Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J (2007) 28:1598–1660.
[Free Full Text] - Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol (2007) 50:e1–e157.
[Free Full Text] - Mehta SR, Cannon CP, Fox KA, Wallentin L, Boden WE, Spacek R, Widimsky P, McCullough PA, Hunt D, Braunwald E, Yusuf S. Routine vs selective invasive strategies in patients with acute coronary syndromes: a collaborative meta-analysis of randomized trials. JAMA (2005) 293:2908–2917.
[Abstract/Free Full Text] - Bavry AA, Kumbhani DJ, Rassi AN, Bhatt DL, Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of contemporary randomized clinical trials. J Am Coll Cardiol (2006) 48:1319–1325.
[Abstract/Free Full Text] - Mandelzweig L, Battler A, Boyko V, Bueno H, Danchin N, Filippatos G, Gitt A, Hasdai D, Hasin Y, Marrugat J, Werf Van de F, Wallentin L, Behar S, Euro Heart Survey Investigators. The second Euro Heart Survey on acute coronary syndromes: characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004. Eur Heart J (2006) 27:2285–2293.
[Abstract/Free Full Text] - Mehta RH, Roe MT, Chen AY, Lytle BL, Pollack CV Jr, Brindis RG, Smith SC Jr, Harrington RA, Fintel D, Fraulo ES, Califf RM, Gibler WB, Ohman EM, Peterson ED. Recent trends in the care of patients with non-ST-segment elevation acute coronary syndromes: insights from the CRUSADE initiative. Arch Intern Med (2006) 166:2027–2034.
[Abstract/Free Full Text] - Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi F. A comparison of low-molecular weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med (1997) 337:447–452.
[Abstract/Free Full Text] - Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Luna Bayes De A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI 11B) trial. Circulation (1999) 100:1593–1601.
[Abstract/Free Full Text] - The SYNERGY Trial Investigators. Enoxaparin vs unfractionated heparin in high risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA (2004) 292:45–54.
[Abstract/Free Full Text] - Mahaffey KW, Cohen M, Garg J, Antman E, Kleiman NS, Goodman SG, Berdan LG, Reist CJ, Langer A, White HD, Aylward PE, Col JJ, Ferguson JJ 3rd, Califf RM, SYNERGY Trial Investigators. High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin. Outcomes at 6 months and 1 year in the SYNERGY trial. JAMA (2005) 294:2594–2600.
[Abstract/Free Full Text] - Petersen JL, Mahaffey KW, Hasselblad V, Antman EM, Cohen M, Goodman SG, Langer A, Blazing MA, Le-Moigne-Amrani A, de Lemos JA, Nessel CC, Harrington RA, Ferguson JJ, Braunwald E, Califf RM. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA (2004) 292:89–96.
[Abstract/Free Full Text] - White HD, Kleiman NS, Mahaffey KW, Lokhnygina Y, Pieper KS, Chiswell K, Cohen M, Harrington RA, Chew DP, Petersen JL, Berdan LG, Aylward PE, Nessel CC, Ferguson JJ III, Califf RM. Efficacy and safety of enoxaparin compared with unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention in the Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. Am Heart J (2006) 152:1042–1050.[CrossRef][Web of Science][Medline]
- Product information of fondaparinux. www.emea.europa.eu/humandocs/PDFs/EPAR/arixtra/H-403-PI-en.pdf.
- Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA, Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med (2006) 354:1464–1476.
[Abstract/Free Full Text] - Mehta SR, Granger CB, Eikelboom JW, Bassand JP, Wallentin L, Faxon DP, Peters RJ, Budaj A, Afzal R, Chrolavicius S, Fox KAA, Yusuf S. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol (2007) 50:1742–1751.
[Abstract/Free Full Text] - Hamon M, Mehta SR, Steg G, Faxon D, Kerkar P, Rupprecht H, Tanguay J, Afzal R, Yusuf S. Major bleeding in patients with acute coronary syndrome undergoing early invasive management can be reduced by fondaparinux, even in the context of trans-radial coronary intervention: insights from OASIS-5 trial. (Abstract 2654). Circulation (2006) 114:II–552.
- Prescribing information of enoxaparin. www.fda.gov/cder/foi/nda/98/20164S15_Lovenox_prntlbl.pdf.
- Kereiakes DJ, Kleiman NS, Fry E, Mwawasi G, Lengerich R, Maresh K, Burkert ML, Aquilina JW, DeLoof M, Broderick TM, Shimshak TM. Dalteparin in combination with abciximab during percutaneous coronary intervention. Am Heart J (2001) 141:348–352.[CrossRef][Web of Science][Medline]
- Buller CE, Pate GE, Armstrong PW, O'Neill BJ, Webb JG, Gallo R, Welsh RC. Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment. Can J Cardiol (2006) 22:511–515.[Web of Science][Medline]
- Madan M, Radhakrishnan S, Reis M, Paradiso-Hardy FL, Godin-Edgecombe M, Sparling C, Phillips AM, Shanmugasegaram S, Fort S, Naqvi SZ, Cohen EA. Comparison of enoxaparin versus heparin during elective percutaneous coronary intervention performed with either eptifibatide or tirofiban (the ACTION trial). Am J Cardiol (2005) 95:1295–1301.[CrossRef][Web of Science][Medline]
- Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA, OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA (2006) 295:1519–1530.
[Abstract/Free Full Text] - Mehta SR, on behalf of the OASIS 5 6 Steering Committee. Benefit of fondaparinux on mortality, ischemic events and bleeding across the entire spectrum of acute coronary syndromes: results of the combined analysis of OASIS 5 and OASIS 6. Presented at the European Society of Cardiology and World Congress of Cardiology. Hotline Session. 9 April 2006.
- Alexander KP, Chen AY, Roe MT, Newby LK, Gibson CM, Allen-LaPointe NM, Pollack C, Gibler WB, Ohman EM, Peterson ED, CRUSADE Investigators. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA (2005) 294:3108–3116.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||