**3.4 Fragility and anticoagulation**

The interest in information on anticoagulation and fragility is growing, thanks to more available information and a better understanding on the subject that being elderly is not the same as having fragility syndrome. Although many elderly individuals suffer from three frequent criteria, such as physical fatigue, weight loss, and slowness when traveling, these items can be reversed if patients are educated in better nutrition, regulated weekly physical activity, if possible with the supervision of trained staff (aquagym, hiking, Tai Chi, etc.) and in turn prevent sarcopenia with improvements in postural balancing and in this way, falls would be avoided [41].

Age ≥ 75 years provides the crucial points to prevent the probabilities of thromboembolism (TE) and stroke with anticoagulants (OACs), according to the CHA2DS2VASCS score in patients with NVAF.

This data is relevant, since, for example, it was observed in 2018, in Argentina, it had registered 31,700 visits per year to a Hospital Emergency Service with a large dispersion in the age range, the average age of 75 years was recorded [42].

Fumagalli et al. studied frail elderly patients older than 70 years with AF (10%) in 14 European countries; they were divided into three age groups. It was observed that 37% of patients, medicated with DOAC (37%) and 5.7% of individuals who cannot be given anticoagulants, were treated with left atrial appendage closure (LAAC).

Less than 11% of the treating physicians considered age as an individual factor for not medicating with anticoagulants, a fact not sufficiently explained by the authors [43].

In a survey conducted in 41 European centers, patients considered fragile and their influence on the management of arrhythmia was studied. AF was found in 72% of patients.

About 57% were diagnosed as fragile patients; 29% were pre-fragile; and 8% of the studied population was >85 years old, which had a higher number of comorbidities and higher rate of drug use, data that reached statistical significance [44].

In relation to falls and the use of DOACs, two studies were carried out; the first was a retrospective subanalysis of ARISTOTLE. It included 753 patients aged 65–74 years, who suffered falls and had a greater number of comorbidities. An 80% benefit was observed in terms of the reduction of intracerebral hemorrhage (ICH) when compared to this group of patients, the use of apixaban vs. that of warfarin [45].

In the second prospective study, a subanalysis of ENGANGE AF, TIMI 48 where patients were treated with edoxaban or warfarin, patients who had falls and those who did not have it were analyzed.

This observed population group (n = 900), older (average 77 years), with more comorbidities (Charlson Comorbidities Index > 5, CHA2DS2VASC > 5, HAS-BLED > 3, 50% permanent AF), had a reduction in mortality and significant severe bleeding, with a considerable decrease in the dreaded intracerebral hemorrhage (ICH) [46].

In the analysis of a subgroup of ARISTOPHANES, considered the largest retrospective observational study using a US database, from 2013 to 2015, they were a population group of fragile elderly people with NVAF with an average age of 83–84 years. Comparing cohorts of patients medicated with DOACS (apixaban, dabigatran, and rivaroxaban) or warfarin, significant weights were established referring to stroke/ES and MB risks [47].

All patients with AF were 150,487, 34% of these were fragile, 90% had a CHA2DS2VASc score ≥ 4, taken as a high risk of stroke, and in more than 80% a HAS-BLED ≥ 3, was considered a threat to bleeding.

*Anticoagulation - Current Perspectives*

Better response with respect to SEE and stroke risk was found with patients who received apixaban (49%) and rivaroxaban (21%), compared to those treated with warfarin.

In relation to MB, apixaban (38%) and dabigatran (21%) had less bleeding and with regard to rivaroxaban vs. warfarin, in the former, there was a small increase in bleeding.

In the SAFIR Cohort study, 995 fragile elderly people were admitted to 33 centers and then followed for a year, it was sought to compare the use of rivaroxaban vs. warfarin.

This group of elderly people with many comorbidities was made up of 23% of nonagenarian people, almost half suffered from a decrease in kidney function, 77% high blood pressure, 50% malnourished, 41% anemia, 39% dementia, and 27% falls (an average of the different scores: CHA2DS2VASc = 4.8, HAS-BLED = 2.3, minimental test = 21.5, activities of daily life 4.4, CCI = 6.7).

When comparing the two Cohorts (rivaroxaban vs. warfarin), adjusted to comorbidities, age, and previous treatment, fragile elderly patients who used rivaroxaban had a significant reduction in MB of 33%, a lower percentage of ICH of 48%, with no differences in mortality decrease and stroke [48].

So, the use of DOACs in fragile patients is a good therapeutic alternative, due to the wide use in the treatment of these patients, wide therapeutic range, predictable pharmacokinetics, easy administration, and little drug interaction; without the need for frequent monitoring and dose adjustment, what is very important in this age group.

The fragile patient is significantly vulnerable due to the polypharmacy by which the use of DOACs in AF dispenses with therapeutic bridge with low molecular weight heparin and helps expand the range of a better diet, being able to incorporate leafy vegetables, contained with the use of vitamin K antagonist [49].
