Abstract
I read with interest the article by Raccah et al, focusing on the impact of prescribing errors with direct oral anticoagulants (DOACs) on the risk of bleeding in patients with atrial fibrillation (AF). 1
The prevalence of errors, consisting in either unjustified low dosage or inappropriate drugs combinations, with a consequent higher major bleeding risk, appears significantly high (33%), but not surprising, since adhering to clinical reality, as we similarly observe in our routine practice. We totally agree with the authors, who remark the importance of being aware of the potential negative impact of prescribing errors and regular follow-up.
Moreover, a recent retrospective analysis conducted by Chaudhry et al, focusing on outcome of patients ≥80 years receiving low dose DOACs, evidenced in the low dose group a higher all-cause mortality rate, as long as higher rate of major bleeding, while the thromboembolic events were not significantly lower than the warfarin group. 2 These results represent a mirror of clinical practice also in our daily experience.
About these observations, I would like to stress some trends we commonly encounter with patients affected by AF taking DOACs, which we believe many of our colleagues will share:
In elderly patients, the choice of low dosage tends to be overused, especially in “frail” subjects or in patients taking concomitant antiaggregant therapy (the latter sometimes inappropriately maintained), even in the absence of significant HASBLED score or hemorrhagic complications. We often encounter patients taking DOACs low dosages, without fully meeting the appropriate criteria, in these cases, a next suggestion to update the dosages is not so easily accepted, either by the patient or the referring general practitioner. This might be explained by a sort of fear of provoking iatrogenic bleeding, in the forgetfulness that hemorrhagic complications are not directly related either to advanced age or generic physical fragility alone. A factor that undoubtedly contributes to this mismanagement is the presence of different criteria for reduction dose adopted in the trials for the different DOACs. 3 To this is added—ie, regarding dabigatran—the use of expressions such as “increased risk of bleeding” as criteria for dosage reduction, which are generic and at the same time alarming, especially in elderly and frail subjects.
In the selection of DOAC and its relative dose, the risk of bleeding sometimes seems to be felt much more than the ischemic risk by the prescriber, even if we dispose of objective tools which should be our constant guide in weighting the burden of each risk (CHA2vasc score, HASBLED). The consequence in the clinical practice is an attitude in choosing the less aggressive dosages than what would be actually indicated for each DOAC. Moreover, we observed DOAC dose reduction or even suspension in elderly patients with slight worsening of an already known chronica anemia, despite the lack of evidence of hemorrhagic sources at instrumental evaluation (ie, gastroscopy, colonoscopy). Not to mention the most aberrant cases, in which DOAC is suspended indefinitely, replaced with low molecular weight heparin (prescribed indefinitely) or even with what wrongly appears—in the collective immagination—the most innocent of the alternatives, that is cardioaspirin.
We encounter some reluctance by our consultant nephrologists to rely on CrCl (calculated with Cockcroft Gault formula), which can pose problems for a shared selection of the proper dosage. So it happens, for example, that in presence of a CrCl 30-49 mL/min, the choice falls to low dosage of either apixaban, edoxaban or rivaroxaban, even in patients younger than 80s, who may be instead eligible to a full dosage of dabigatran.
This kind of demonization of full dosages of DOACs is quite incomprehensible, since they have introduced just as warfarin competitors, associated with lower intracerebral hemorrhage rates, nevertheless this attitude influences the routine clinical practice. This concept is effectively summed up in an old but still current way of saying, according to which ischemic events are unpredictable, but bleeding might be induced by us.
Finally, we have noticed a subtle tendency to therapeutic inertia during the follow-up visits, on these occasions the therapy risks to be slavishly confirmed, in the absence of significant adverse events. Instead, they represent a fundamental moment for an overall re-evaluation, not only of the right molecule, which can be switched any time to meet the contextual specific needs of the patients but also of proper dosages. The therapeutic situation is, in fact, a dynamic state and many are the variables involved, in addition to age, such as clearance—which has different cut-offs for the various DOACs—weight and concomitant drugs.
With this in mind, our attention must always be high—especially in consideration of the fact that an increasing proportion of patients are elderly and frail—because DOAC therapy constantly rests on a thread of wool, in continuous delicate balance between ischemia and bleeding, but the weapons to prevent both of them are there, it’s up to us to use the right ones.
