"The mortality benefit with fondaparinux compared to enoxaparin and the European authorisation of fondaparinux may allow physicians to consider a new treatment option for appropriate ACS patients," said Andrew Zambanini, MD, Director, Cardiovascular and Metabolic Medicine Development Centre, GSK. "GSK is committed to continuing to support therapies for cardiac patients around the world."
This authorisation coincides with newly published European Society of Cardiology guidelines that have given only fondaparinux the highest (grade 1A) recommendation for the anticoagulant treatment of UA/NSTEMI patients, as long as a decision between early invasive (<72 hours) or conservative strategy is pending.3
Authorisation of the ACS indication was based on positive results from two pivotal Phase III trials including more than 32,000 patients that evaluated fondaparinux versus enoxaparin (OASIS 5) or standard therapies of unfractionated heparin or placebo (OASIS 6) for the treatment of selected patients with ACS.4,5
The company’s application for the ACS indication was submitted to European regulators on 31 July, 2006. On 21 June, 2007, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for fondaparinux in patients with ACS.6
UA/NSTEMI Fondaparinux is indicated for the treatment of unstable angina or non-ST segment elevation myocardial infarction (UA/NSTEMI) in patients for whom urgent (<120 minutes) invasive management (PCI) is not indicated.
Data from OASIS 5, one of the largest clinical trials ever conducted in patients with ACS, showed that fondaparinux is of similar efficacy to LOVENOX®/ CLEXANE®*** (enoxaparin) in patients suffering unstable angina and non-ST elevation myocardial infarction, and was associated with a significant lower risk of bleeding at day 9 and a significant mortality benefit at day 30.
The OASIS 5 clinical trial compared fondaparinux 2.5mg once daily to enoxaparin 1mg/kg twice daily in patients with UA/NSTEMI.4 Fondaparinux was associated with a significant 48% (p<0.001) reduction in major bleeding vs. enoxaparin (2.2% and 4.1% incidence, respectively) up to 9 days.4 The study also showed that fondaparinux significantly reduces mortality compared to enoxaparin at one month.4 Mortality rates at one month were 2.9 % in the patient group receiving fondaparinux and 3.5% in the patient group receiving enoxaparin, representing a 17% reduction (p=0.02) in favour of fondaparinux.4
STEMI Fondaparinux is indicated for the treatment of STEMI in patients who are managed with thrombolytics or who initially are to receive no other form of reperfusion therapy.
Data from OASIS 6, one of the largest clinical trials conducted in patients with STEMI, showed that fondaparinux is more efficacious than standard therapy and that this improved efficacy was achieved with no increased risk of bleeding compared to standard therapies.
OASIS 6 compared fondaparinux to standard therapies (unfractionated heparin or placebo) in STEMI patients. The overall results of the OASIS 6 study demonstrated greater efficacy of fondaparinux compared to standard therapy in reducing risk of death or recurrent heart attack (risk reduction of 14% at day 30, p=0.008).5
Acute Coronary Syndromes People with ACS have an increased immediate and long-term risk of recurrent heart attack and cardiac death.7
About fondaparinux Fondaparinux is the first in a class of antithrombotics that selectively inhibits Factor Xa, a central protein in the coagulation process. In the treatment of thrombosis, Factor Xa plays a central role in the generation of thrombin, a protein in blood that facilitates blood clotting.
Important Safety Information: Contraindications Fondaparinux is contraindicated in patients with severe renal impairment, active clinically significant bleeding, acute bacterial endocarditis and patients with hypersensitivity to fondaparinux sodium.
Warnings When epidural/spinal anaesthesia or spinal puncture is employed, patients anticoagulated with low-molecular-weight heparins, heparinoids or fondaparinux sodium are at risk of developing an epidural or spinal haematoma, which can result in long-term or permanent paralysis. The risk of these events may be higher with postoperative use of indwelling epidural catheters or concomitant use of drugs affecting haemostasis. Spinal/epidural anaesthesia should not be used concurrently with fondaparinux for the treatment of VTE.
Fondaparinux is not intended for intramuscular administration.
Fondaparinux should be used with caution in all patient groups with increased risk of bleeding, such as those with congenital or acquired bleeding disorders (e.g. platelet count <50,000/mm3), active ulcerative gastrointestinal disease and recent intracranial haemorrhage or shortly after brain, spinal or ophthalmic surgery and in special patient groups as outlined below. This includes the elderly, and patients with moderate renal or severe hepatic impairment. Fondaparinux should be used with caution in those patients weighing less than 50kg (less than 110lbs). For VTE treatment and prevention, fondaparinux should not be co-administered with drugs that may increase the risk of bleeding. For the treatment of ACS, fondaparinux should be used with caution in patients who are being treated with other agents that may increase the risk of bleeding.
The efficacy and safety of fondaparinux in patients with heparin-induced thrombocytopenia type II has not been studied. Thrombocytopenia can occur during a treatment with fondaparinux and if the platelet count falls below 100,000/mm3, fondaparinux should be discontinued.
In STEMI patients undergoing primary PCI and in UA/NSTEMI patients undergoing urgent PCI (<120 minutes), the use of fondaparinux prior to and during PCI is not recommended. The use of fondaparinux as the sole anticoagulant during PCI is not recommended, therefore UFH should be used according to local practice. There are limited data on the use of UFH during non-primary PCI in patients treated with fondaparinux.
Clinical trials have shown a low but increased risk of guiding catheter thrombus in patients treated with fondaparinux for anticoagulation during PCI compared to control.
About GlaxoSmithKline GlaxoSmithKline – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information visit www.gsk.com.
