Fondaparinux Post-Streptokinase in MI
Fondaparinux 2.5 mg subcutaneously once daily is an acceptable alternative anticoagulant after streptokinase administration in STEMI patients who are not planned for an invasive approach, with demonstrated reductions in death and reinfarction compared to placebo or unfractionated heparin. 1
Primary Recommendation for Post-Fibrinolytic Anticoagulation
In patients with STEMI who received fibrinolytic therapy (including streptokinase) and are not planned for an invasive approach, enoxaparin is the preferred anticoagulant over unfractionated heparin (UFH). 1 However, fondaparinux represents a reasonable alternative when enoxaparin is contraindicated or unavailable. 1
Evidence Supporting Fondaparinux After Streptokinase
In the OASIS-6 trial of patients with STEMI treated with thrombolytic agents (predominantly streptokinase), fondaparinux significantly reduced the primary endpoint of death or reinfarction at 30 days, including significant reductions in mortality, reinfarction, and severe bleeding when compared with placebo or UFH. 1
The subgroup analysis of 5,436 patients receiving thrombolytics in OASIS-6 demonstrated that fondaparinux reduced death or MI at 30 days (HR 0.79,95% CI 0.68-0.92) with consistent reductions in both mortality and reinfarction. 2
Severe bleeding was significantly reduced with fondaparinux compared to control (HR 0.62, CI 0.40-0.94), resulting in a favorable benefit-risk balance. 2
Dosing Regimen
Fondaparinux should be administered as 2.5 mg IV bolus initially, followed by 2.5 mg subcutaneously once daily until hospital discharge or for a maximum of 8 days (whichever comes first). 3, 4, 2
Renal Considerations
Fondaparinux is contraindicated when creatinine clearance is <30 mL/min and alternative anticoagulants should be used. 3, 1
Creatinine clearance should be calculated using the Cockcroft-Gault formula rather than the MDRD equation. 1
No dose adjustment is required based on age alone; the 2.5 mg once-daily dose remains standard regardless of patient age. 3
Critical Contraindication: Primary PCI
Fondaparinux should NOT be used as the sole anticoagulant to support PCI because of the risk of catheter thrombosis (Class III: Harm recommendation). 1, 3
Managing Transition to PCI
If a patient on fondaparinux requires PCI, supplemental UFH must be added (50-100 U/kg bolus) to prevent catheter-related thrombosis. 3, 5
In OASIS-6, a higher rate of guiding-catheter thrombosis and coronary complications with fondaparinux were observed when used during PCI without supplemental anticoagulation. 1
The OASIS-5 trial showed an increased rate of catheter-related thrombus with fondaparinux compared with enoxaparin (0.9% versus 0.4%). 1
Comparison with Preferred Agent (Enoxaparin)
While fondaparinux is acceptable, enoxaparin remains the preferred anticoagulant after fibrinolytic therapy for patients not undergoing immediate invasive management. 1
In the ExTRACT-TIMI 25 study, enoxaparin reduced death or nonfatal recurrent MI at 30 days (9.9% versus 12.0% with UFH) in 20,506 patients with STEMI receiving fibrinolytic therapy. 1
Enoxaparin demonstrated net clinical benefit (death, complication of MI, or major bleeding) compared with UFH (10% versus 15%; P=0.03). 1
Common Pitfalls to Avoid
Never use fondaparinux as the sole anticoagulant during PCI - this is explicitly contraindicated due to catheter thrombosis risk. 1, 3
Do not switch between anticoagulants unnecessarily - switching increases bleeding risk. 6, 5
Avoid fondaparinux in severe renal dysfunction (CrCl <30 mL/min) due to renal clearance and accumulation risk. 1, 3
Do not extrapolate dosing or safety data from other anticoagulants - each agent has distinct pharmacologic properties. 1
Management of Bleeding Complications
If bleeding occurs while on fondaparinux:
Discontinue fondaparinux immediately and assess bleeding severity and location. 6
Provide hemodynamic support with fluid resuscitation and blood products as needed for major bleeding. 6
Note that protamine sulfate does not reverse fondaparinux (it only reverses UFH if given as supplemental therapy). 6
Local pressure and hemostatic measures may be sufficient for minor bleeding. 6