title: Clinical benefits of pharmacogenetic algorithm-based warfarin dosing: meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Pharmacogenetic (PG) algorithms were proposed to predict warfarin therapeutic dose more accurately. However, the clinical efficacy of the strategy over the standard treatment was not consistently proven.
  
  
  METHODS
  We conducted a meta-analysis of the published randomized controlled trials (RCTs) comparing PG algorithm-based warfarin dosing (PG group) with clinical or standard protocols (STD group). The PUBMED, EMBASE, Cochrane Library and Web of Science databases were searched up to June 2014.
  
  
  RESULTS
  A total of 10 RCTs were retrieved for the meta-analysis with the inclusion of 2,601 participants. Primary analysis showed both major bleeding (2.65% versus 4.75%; RR: 0.57, 95% CI: 0.37- 0.90, P=0.02) and thromboembolic events (0.59% versus 1.88%; RR: 0.38, 95% CI: 0.17-0.85, P=0.02) were significantly lower in PG than in STD group. There was a trend towards increased percentage of time in therapeutic range (%TTR) [mean difference (MD): 4.65, 95% CI: 0.01- 9.29, P=0.05] in PG group, but no difference was observed for over-anticoagulation (INR>4). Subgroup analyses showed significant reduction of both major bleeding and thromboembolic events in PG group when the follow-up time was more than 1 month. After stratified by different PG algorithms, significant major bleeding reduction could be found in PG group when warfarin indication or co-medication of amiodarone was integrated in the algorithms.
  
  
  CONCLUSIONS
  PG algorithm-guided warfarin anticoagulation is beneficial for the reduction of both major bleeding and thromboembolic events compared with standard dosing strategy. The benefits may be prominent in patients with longer follow-up time, or guided by refined PG algorithms.
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors: Xiaoqi
authors: X
authors: Li
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors: Jie
authors: J
authors: Yang
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors: Xuyun
authors: X
authors: Wang
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors: Qiang
authors: Q
authors: Xu
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors: Yuxiao
authors: Y
authors: Zhang
authors: Department of Cardiology, Institute of Geriatric Cardiology, General Hospital of Chinese People's Liberation Army, Beijing 100853, China. Electronic address: yintong2000@yahoo.com.
authors: Tong
authors: T
authors: Yin
mesh_terms: D000465:Algorithms; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000097:blood / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014859:Warfarin
keywords: Bleeding; Meta-analysis; Pharmacogenetics; Thromboembolism; Warfarin