Swedish Registry Confirms Fondaparinux Advantage Over LMWH in NSTEMI Patients

February 20, 2015

STOCKHOLM, SWEDEN — The use of fondaparinux (Arixtra, GlaxoSmithKline) is associated with a lower risk of in-hospital bleeding and mortality when compared with low-molecular-weight heparin (LMWH) in patients with non–ST-segment elevation MI (NSTEMI), according to the results of large Swedish registry[1].

Overall, 1.1% of patients who received fondaparinux, a factor Xa inhibitor, had a bleeding event, compared with 1.8% of NSTEMI patients who received LMWH, a difference that was statistically significant. For mortality, 2.7% of patients treated with fondaparinux died in-hospital vs 4.0% of those who received LMWH, a difference that was also statistically significant.

The results were similar among patients who underwent early PCI and among those with varying degrees of renal function, report Dr Karolina Szummer (Karolinska University Hospital, Stockholm, Sweden) and colleagues in the February 17, 2015 issue of the Journal of the American Medical Association.

The results of the study confirm the main findings from the OASIS-5 study, published in 2006 and reported by heartwire , which showed that fondaparinux was noninferior to enoxaparin, an LMWH, for the reduction of early ischemic events but was significantly better at reducing major bleeding. In OASIS-5, treatment with fondaparinux was associated with a significant reduction in mortality at 30 and 180 days.

The Swedish registry included 14 791 patients with NSTEMI treated with fondaparinux and 25 825 treated with LMWH. Compared with OASIS-5, patients in Swedish registry had lower rates of hypertension and a more frequent history of MI and stroke.

"Outside of a trial setting, the treatment is given to a much more heterogeneous patient population and the treating centers and physicians are less selected," write Szummer and colleagues. "Thus, the balance between benefit and risk can differ between a randomized clinical trial and experience in a nontrial, routine, clinical-care setting."

Benefit Confirmed in Registry Data

At 30 and 180 days, patients in the fondaparinux arm had a significantly lower risk of severe bleeding and death than those treated with LMWH. In total, 4.2% and 8.3% of the fondaparinux-treated patients died at 30 and 180 days, respectively, compared with 5.8% and 11.8% of the LMWH-treated patients. The mortality difference at 30 and 180 days was statistically significant.

Regarding ischemic end points, there was no difference in the rates of MI or stroke at 30 or 180 days between the two treatment arms.

Individuals who received fondaparinux were more likely to undergo early PCI. Despite differences in adjunctive PCI-related therapy, there was no significant difference in outcomes between those who underwent PCI during hospitalization for NSTEMI and those who did not. Overall, 42% of the NSTEMI patients underwent PCI.

Patients with impaired renal function had a significant fivefold higher rate of severe bleeding, but bleeding rates were lower in-hospital and at 30 days among those treated with fondaparinux vs those who received LMWH. However, the confidence intervals were wide and not statistically significant for those with the most impaired renal dysfunction. Similar results were observed for in-hospital mortality and death at 30 days among those with renal dysfunction.

The authors point out that patients with renal dysfunction are at high risk of bleeding events, and if bleeding can be prevented this might translate into lower mortality.

"However, even though the odds of bleeding were consistently lower across all renal-function categories, the lower mortality with fondaparinux compared with LMWH was not significant in those with worst renal function," write Szummer and colleagues. "This may indicate that the elevated risk of death in those with the lowest renal-function category is explained by other mechanisms unrelated to bleeding."

The European Society of Cardiology (ESC) recommends fondaparinux as a first-choice anticoagulant for ACS patients treated noninvasively or with PCI.

In the US, however, the American College of Cardiology/American Heart Association recommends an anticoagulant for patients with NSTEMI, either fondaparinux or enoxaparin, but only for those not undergoing PCI. In OASIS-5 and OASIS-6, as reported by heartwire , the formation of catheter thrombus was more common in PCI patients receiving fondaparinux than enoxaparin.

The study was sponsored by the Swedish Foundation for Strategic Research and the Swedish Heart and Lung Foundation. Szummer reports receiving lecture fees from AstraZeneca. Disclosures for the coauthors are listed in the article.

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