Factor Xa inhibitors for acute coronary syndromes.
BACKGROUND
The activation of coagulation mechanisms plays a central role in the pathogenesis of acute coronary syndromes (ACS). Administration of unfractionated heparin (UFH) and low molecular weight heparins (LMWH), agents preventing the progression of thrombus formation, is a crucial therapeutic strategy. However, some limitations related to their use have recently stimulated the development of new synthetic agents.


OBJECTIVE
To evaluate the clinical efficacy and safety of factor Xa inhibitors for treatment of ACS compared to UFH or LMWH.


METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library (Issue 1, 2008), PubMed, EMBASE and LILACS as well as the publications from International Congresses and the reference lists of the selected studies in December 2008.


METHODS
We used randomized controlled trials (RCTs) comparing factor Xa inhibitors to UFH or LMWH during the course of ACS. Outcome measures included all-cause mortality, myocardial infarction, re-infarction, ischemia recurrence, and adverse events.


METHODS
The selection, quality assessment and data extraction of the included trials were done independently by two authors and disagreements were resolved by consensus. Data were analysed by the use of risk ratio (RR) with 95% confidence interval (CI), and the numbers needed to treat (NNT) were reported as needed.


RESULTS
A total of four RCTs involving 27,976 subjects were included. Fondaparinux was the only factor Xa inhibitor identified in our included RCTs. Fondaparinux appeared to be related to a lower risk in all-cause mortality at 90 to 180 days (RR 0.89; 95% CI 0.81 to 0.97), especially in the group where enoxaparin (a LMWH) was the control drug. Fondaparinux was also associated with a lower risk in major and minor bleeding at 30 days compared to enoxaparin (RR 0.63, 95% CI 0.55 to 0.73; RR 0.34, 95% CI 0.28 to 0.43, respectively), but not when compared to UFHs (RR 1.41; 95% CI 0.49 to 4.10; RR 0.70, 95% CI 0.14 to 3.39 respectively).


CONCLUSIONS
The therapeutic efficacy of factor Xa inhibitors in ACS seemed to be related to a reduced risk in all-cause mortality at 90 to 180 days, with a better safety profile than enoxaparin in terms of reduce incidence of major and minor bleeding.
Coronary Care Unit, Hospital de Clinicas, Universidad de Buenos Aires, Avenida Cordoba 2351 Piso Sala 1, Ciudad Autonoma Buenos Aires, Capital Federal, Argentina.
Viviana
V
Brito
Agustín
A
Ciapponi
Joey
J
Kwong
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000925:Anticoagulants / Q000627:therapeutic use*; D003328:Coronary Thrombosis / Q000517:prevention & control; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006493:Heparin / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D011134:Polysaccharides / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux