Due to the risk ofcatheter thrombosis, fondaparinux should not be used alone for a patientundergoing primary percutaneous coronary intervention during acute coronarysyndrome (ACS).1 The 2013 ACCF/AHA guidelines made thisrecommendation according to the results of the OASIS-6 trial, which showed anincrease in the rates of guiding catheter thrombus when fondaparinux was usedwithout unfractionated heparin (UFH).2 Several trials have beenconducted to test the safety and efficacy of fondaparinux compared to otheranticoagulant medications for early invasive management strategies of ACS.
In the OASIS-5 trial,enoxaparin and fondaparinux were compared for the primary efficacy outcome of death,myocardial infarction (MI), or refractory ischemia at nine days in patientswith ACS with non-ST segment elevation (NSTEMI).3 While fondaparinuxproved to be statistically insignificant in the trial’s primary outcomes, thedrug was superior clinically at reducing the rate of death as well as theamount of bleeding when compared to enoxaparin. The trial stated that reasonsfor increased bleeding in enoxaparin are not known, but may be correlated tothe high dose that was used.3 With the results of this study, fondaparinuxappeared to be the drug of choice for PCI patients for short term treatment.
However,the occurrence of catheter thrombus was still higher in patients who were onfondaparinux versus those who were on enoxaparin.4 In aprospectively planned analysis of the OASIS-5 trial, it was concluded that thelower incidence of thrombi occurrence in those on enoxaparin may have beenassociated with the use of UFH along with enoxaparin.4 Because onlycertain endpoints were evaluated, the recommendation of using fondaparinux inintervention therapy was not established through the conclusion of this trial.Further investigationinto the use of fondaparinux was conducted in the OASIS-6 trial with patientswho had ST-segment elevation myocardial infarction.2 Compared topatients who were on either placebo or UFH, patients who were on fondaparinuxhad a reduced composite of death and myocardial infarction 9 days and 30 daysafter the PCI was performed.2 The study showed that fondaparinux wasa better treatment plan compared to usual care as it reduced death,reoccurrence of MI, and cardiac tamponade all without increasing the chance ofbleeding or stroke.
2 A prospective cohort study that was conductedin Sweden concluded that in patients with NSTEMI, fondaparinux was moreadvantageous at reducing major bleeding events and death up to 180 days afterinitial use when compared to low molecular weight heparin.5 Theseresults are consistent with the OASIS-5 trial.2 When fondaparinuxwas used as the sole anticoagulant agent, the rate of thrombi formation was increasedcompared to other drugs as it is a factor Xa inhibitor only. This allows factorIIa to still develop clots; therefore, adding a factor IIa inhibitor such asUFH improves drug therapy.
2 In terms of catheter thrombosis.patients who were treated with UFH had low incidences of experiencingcomplications.2 Comparatively, patients who were treated withfondaparinux prior to receiving a PCI and was then given UFH also experienced alow rate of catheter thrombosis.2 This confirmed that fondaparinuxused in combination with UFH for patients undergoing intervention therapy issafe and effective. This combination therapy seems to be the most beneficial asit reduces mortality and morbidity risk in PCI patients.
The correct dosage of UFHwas later determined in the FUTURA/OASIS-8 randomized trial.7 TheEuropean Society of Cardiology has a class IB recommendation on the use offondaparinux with UFH in NSTEMI PCI patients.6 Like the ACCF/AHAguidelines, the safest recommendation for patients undergoing PCI isbivalirudin combination therapy as an alternative to UFH.6 Therecommendation that fondaparinux should not be used as a sole agent to treatACS patients who will undergo PCI is consistent in all guidelines.1.6Based off the evidence and data provided, I would agree with the recommendation.