title: Safety of warfarin in "high-risk" populations: A meta-analysis of randomized and controlled trials.
abstract: BACKGROUND
  Few data are available about safety of vitamin K antagonists (VKAs) in patients with clinical/demographic characteristics predisposing to an increased risk of bleeding. We performed a meta-analysis to evaluate the safety of VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) in the following subgroups of "high-risk" patients: elderly patients, patients with low body weight and patients with impaired renal function.
  
  
  METHODS
  Major electronic databases were systematically searched to identify randomized controlled trials (RCTs) addressing this issue. Pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for each outcome using a random effects model.
  
  
  RESULTS
  Eleven RCTs for a total of 41,015 patients treated with VKAs (25,901 with AF and 15,114 with VTE) were included. We found a significant association between age>75years and bleeding in patients receiving VKAs (RR: 1.62, 95%CI: 1.28-2.05; P<0.0001). Moreover, the prevalence of bleeding events under VKAs was significantly higher in patients with low body weight (RR: 1.20, 95%CI: 1.03-1.40; P=0.02) and in those with impaired renal function (RR: 1.59, 95%CI: 1.30-1.94; P<0.00001). Results were confirmed when separately analyzing data on AF and VTE. Regression models showed that treatment duration did not impact on the differences found in the safety profile of VKAs in different settings analyzed.
  
  
  CONCLUSIONS
  Results of our meta-analysis suggest an increased risk of bleeding complications in "high-risk" patients. Although all results are significant, other studies focused on this issue are warranted to further validate these results.
authors.affiliation: Department of Advanced Biomedical Sciences, Division of Cardiology, Federico II University, Naples, Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: dario.diminno@hotmail.it.
authors.forename: Matteo Nicola Dario
authors.initials: MN
authors.lastname: Di Minno
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Ambrosino
authors.affiliation: Department of Clinical and Experimental Medicine, Univesity of Insubria, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dentali
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin
keywords: Anticoagulants; Atrial fibrillation; Hemorrhage; Venous thromboembolism; Warfarin