Back to the future? Re: Risks and benefits of direct oral anticoagulants versus warfarin in a real world setting
DOACs have obvious advantages over warfarin, except for the costs. Strokes and bleedings are very relevant endpoints. Death is the ultimate hard endpoint. The brilliant analysis of Yana Vinogradova and Julia Hippisley-Cox et al (BMJ 04 July 2018, https://doi.org/10.1136/bmj.k2505), motivates important reflexion on the Risk/Benefit balance of these modern and useful cardiovascular drugs (DOACs).
Most of the practice changing drugs in the last two decades follow a pattern: THE RULE 3-30. Their relative risk reduction (RRR) is 30 percent or more (not less than 20 pc), the absolute risk reduction is 3% or more (not less than 2 pc) and the number needed to treat for benefit (NNT) is 30 or less, up to 50. In the case of death, the NNT can be round 100.
Their number needed to harm (NNH) should be 3 times or more their NNT, in the case of death 300 or more.
It is worrisome to see in the case of DOACs vs Warfarin that the NNT at 2 years (Tables 3 and 4) for bleedings (including intracranial) for apixaban and dabigatran oscillate between 60 and 150; for rivaroxaban 185 (intracranial bleed, used without atrial fibrillation).
The NNH for mortality is 23 to 70 for rivaroxaban (NNH much lower than NNT; it should be the opposite).
The Age-sex standardised rate per 1000 py of mortality for warfarin is up to 44.6; for apixaban is 53.5 up to 61.9.
The NNH for mortality for apixaban vs warfarin can be calculated to be 58 to 112 (similar pattern: NNH lower than NNT).
This important study is a ringing bell (or even a red flag) to investigate more the long term safety of DOACs: which are the safest vs warfarin, at which doses, for how long. Their important advantages must be weighed again in view of this new evidence.
Prof. Enrique Sánchez-Delgado, M.D.
Internal Medicine-Clinical Pharmacology and Therapeutics
Hospital Vivian Pellas
Competing interests: No competing interests