Safety of direct oral anticoagulants in real-world clinical practice: translating the trials to everyday clinical management

Expert Opin Drug Saf. 2019 Mar;18(3):187-209. doi: 10.1080/14740338.2019.1578344. Epub 2019 Feb 18.


Direct oral anticoagulants (DOACs) may be regarded as some of the most successful innovations in recent times. These drugs which were specifically developed to overcome the challenges posed by warfarin did just that and in the process, have changed the outlook towards stroke prevention with anticoagulation. The decade of experience with these drugs that has resulted in the availability of large scale data on their safety profile has aided this. Areas covered: This review examines existing real-world studies (RWS) and their interpretation to better appreciate how they either complement or contradict findings from the hallmark trials. Specific focus has been made on the safety of DOACs, on their risks of major bleeding, intra-cranial haemorrhage (ICH), gastro-intestinal (GI) bleeding and all-cause mortality compared to warfarin and each other. DOAC use in the elderly and other sub-groups are briefly discussed. Expert opinion: Results for safety outcomes according to 'real world evidence' (RWE) are in-keeping with randomised controlled trials (RCTs) and currently, all 4 DOACs have been deemed at least as effective as warfarin, while demonstrating superiority in some aspects. While real world studies act as a complementary source of knowledge, traditional RCTs remain the gold standard for determining cause-effect relationships.

Keywords: DOACs; Oral anti-coagulants; apixaban; atrial fibrillation; dabigatran; edoxaban; randomised controlled trials; real world evidence; rivaroxaban; safety.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Randomized Controlled Trials as Topic
  • Stroke / prevention & control
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects


  • Anticoagulants
  • Warfarin