Is anyone actually still using this drug? If so, why? There has been nothing but an endless progression of bad news associated with this medication – from Boehringer Ingelheim settling a massive lawsuit, the authors from RE-LY admitting they “missed” additional adverse events for a second time, and, now, further evidence describing flawed real-world effectiveness contrary to its supposed demonstrated efficacy.
The RE-LY trial showed non-inferiority for dabigatran at stroke prevention in non-valvular atrial fibrillation, but appeared to place patients at significantly lower risk of bleeding compared with warfarin. One of the critiques of RE-LY, however, is the patients were not appropriately representative of the general population at-risk for atrial fibrillation. By omitting chronic kidney disease and enrolling a generally white population in Europe, the generalizability of their findings is ultimately impaired.
And, thus, we see the fruits of such critiques. This is a retrospective cohort of Medicare beneficiaries prescribed either dabigatran or warfarin for atrial fibrillation. Based on propensity matched samples of 1,302 dabigatran users and 8,102 warfarin users, major bleeding of the dabigatran cohort exceeded that of the warfarin cohort – 9.0% (95% CI 7.8 – 10.2) versus 5.9% (95% CI 5.1 – 6.6). Risks were increased in the elderly, blacks, those with chronic kidney disease, and those on concomitant anti-platelet therapy.
So, we have a lesson – one of effectiveness versus efficacy, or one that’s an indictment of the original RE-LY study protocol. Medications should not be expected to perform the same in general use as they do in clinical trials – even those with tens of thousands of patients, such as RE-LY. Independent, confirmatory study ought be mandatory to ensure the safety of the public.
“Risk of Bleeding With Dabigatran in Atrial Fibrillation”
Addendum:
Walid Gellad on Twitter points out this study in Circulation, published last week to much lesser fanfare, which uses a larger Medicare sample to come to the opposite conclusion – that dabigatran is better than, and safer than, warfarin. Which is correct? A subject for continued debate, to be certain. The correct answer is probably somewhere in between – dabigatran is safer for some, but more dangerous for others. However, given the lack of reversal – wouldn’t a Factor Xa inhibitor be a better choice, regardless?