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Semin Thromb Hemost
DOI: 10.1055/a-2716-5675
Review Article

Anticoagulants: Evidence-Based Medicine, Not Always Ethical

Authors

  • Francesco Marongiu

    1   Department of Internal Medicine, University of Cagliari, Cagliari, Italy
    2   Fondazione Arianna, Anticoagulazione.it, Bologna, Italy

  • Antonella Mameli

    3   Transfusion Medicine Unit, Azienda Socio Sanitaria Locale n. 6 San Gavino, Cagliari, Italy

  • Silvia Marongiu

    3   Transfusion Medicine Unit, Azienda Socio Sanitaria Locale n. 6 San Gavino, Cagliari, Italy

  • Doris Barcellona

    4   Department of Medical Sciences and Public Health, Internal Medicine, University of Cagliari, Cagliari, Italy
    5   Haemostasis and Thrombosis Departmental Unit, Teaching Hospital of Cagliari, Cagliari, Italy
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Abstract

Evidence-based medicine (EBM) has created a revolutionary system for disseminating a scientific method. However, the scientific rigor of early EBM did not demonstrate any concern for ethics in the management of venous thromboembolism (VTE) and atrial fibrillation (AF). We critically reviewed whether EBM and ethical principles have always converged, focusing on the development and use of anticoagulants, by analyzing key trials in the treatment and prevention of those conditions. Moreover, we aimed to explore whether methodological rigor has sometimes overshadowed clinical ethics, particularly in the context of placebo-controlled trials. In our opinion, even if randomized clinical trials (RCTs) are considered the first step in the hierarchy of EBM, several of these appear unjustified, as observational studies had already indicated that anticoagulants (heparins and anti-vitamin K drugs [VKA]) were considered effective in the treatment and prevention of thrombotic diseases, such as VTE and AF. The use of a placebo was often unethical. This has caused unjustified mortality and morbidity to many people when a placebo has been used as a control. Even the methodology in favor of the non-inferiority margin is questionable, as it is considered satisfactory to maintain at least half of the efficacy of the current drug. In other words, a bonus for the new medicines seems to be always generous, and in the future, biocreep phenomenon is destined to be dangerous. The belief that only RCTs, even if of paramount importance, produce trustworthy results and that observational studies are misleading can lead to a disadvantage in patient care, clinical investigation, and the education of health care professionals (visual abstract).

Keywords

venous thromboembolism - atrial fibrillation - randomized controlled trials - observational studies - non-inferiority trials


Publication History

Received: 08 July 2025

Accepted: 03 October 2025

Article published online:
23 October 2025

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