title: Low-dose of oral factor Xa inhibitors in patients with a recent acute coronary syndrome: a systematic review and meta-analysis of randomized trials.
abstract: BACKGROUND
  Recently, randomized controlled trials (RCTs) have shown that therapy with new oral activated factor X (Xa) inhibitors in acute coronary syndrome (ACS) yielded a reduction of ischemic events. However, this therapy was associated with a dose-related increase in major bleeding complications. We aimed to perform a systematic review and meta-analysis to appraise the clinical efficacy and safety of the lowest doses of oral factor Xa inhibitors compared with placebo in patients after a recent ACS.
  
  
  METHODS
  The primary endpoint was cardiovascular mortality. The rate of new myocardial infarction (MI) was the secondary efficacy endpoint, whereas major bleeding complications were recorded as a safety endpoint. Five RCTs were included in the meta-analysis enrolling a total of 25,643 patients.
  
  
  RESULTS
  There was no significant difference in mortality between patients treated with new antithrombotics compared with those receiving the standard therapy: odds ratio (OR), [95% confidence interval (CI)] = 0.97 [0.72-1.31], p = 0.86. Recurrent MI rates were decreased in the anti-Xa group: OR [95%CI] = 0.86 [0.76-0.98], p = 0.02, number needed to treat (NNT) = 189. The administration of new oral anticoagulants was associated with a strongly increased risk of major bleedings compared with the standard treatment: OR [95%CI] = 3.24 [2.29-4.59], p < 0.001, number needed to harm (NNH) = 104; similarly, intracranial bleeding rates were significantly higher in the anti-Xa arm.
  
  
  CONCLUSIONS
  The addition of the new oral anticoagulants on top of standard therapy in the setting of ACS results in an excessive risk of major bleedings without any clear evidence of outweighing clinical benefits.
authors.affiliation: Department of Cardiology and Internal Medicine, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Obonska
authors.forename: Eliano Pio
authors.initials: EP
authors.lastname: Navarese
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lansky
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tarantini
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossini
authors.forename: Marek
authors.initials: M
authors.lastname: Kozinski
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Pasquale
authors.forename: Bartosz
authors.initials: B
authors.lastname: Górny
authors.forename: Anna
authors.initials: A
authors.lastname: Szczesniak
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kowalewski
authors.forename: Paul Alfred
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Jacek
authors.initials: J
authors.lastname: Kubica
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality*; D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors
keywords: ACS; Acute coronary syndrome; BID; HR; MI; Meta-analysis; OR; Oral anti Xa anticoagulants; QD; RCTs; TIMI; X activated; Xa; acute coronary syndrome; hazard ratio; myocardial infarction; odds ratio; once daily; randomized controlled trials; thrombolysis in myocardial infarction; twice per day