Original Study
Safety of Direct Oral Anticoagulants and Vitamin K Antagonists in Oldest Old Patients: A Prospective Study

https://doi.org/10.1016/j.jamda.2018.04.017Get rights and content

Abstract

Objective

The safety of direct oral anticoagulants (DOACs) in oldest old patients with nonvalvular atrial fibrillation (NVAF) in daily clinical practice has not been systematically assessed. This study examined the safety of DOACs and dicumarol (a vitamin K antagonist) in NVAF geriatric patients.

Design

Prospective study from January 2010 through June 2015, with follow-up through January 2016.

Setting

Geriatric medicine department at a tertiary hospital.

Participants

A total of 554 outpatients, 75 years or older, diagnosed of NVAF and starting oral anticoagulation.

Measurements

The main outcome was bleeding, which was classified into major (including those life-threatening) and nonmajor episodes. Statistical analyses were performed with Cox regression.

Results

A total of 351 patients received DOACs and 193 dicumarol. Patients on DOACs were older, with more frequent comorbidities, mobility limitation and disability in activities of daily living, as well as higher mortality, than those treated with dicumarol. The incidence of any bleeding was 19.2/100 person-years among patients on DOACs and 13.7/100 person-years on dicumarol; corresponding figures for major bleeding were 5.2 for those on DOACs, and 3.3 for those on dicumarol. In crude analyses, hazard ratios (95% confidence intervals) for any bleeding, and for mayor bleeding in patients on DOACs vs dicumarol were 1.60 (1.04-2.44) and 2.22 (0.88-5.59), respectively. Excess risk of bleeding associated with DOACs vs dicumarol disappeared after adjustment for clinical characteristics, so that corresponding figures were 1.19 (0.68-2.08) and 1.01 (0.35-2.93). Results did not vary across subgroups of high-risk patients.

Conclusion

In very old patients with NVAF, the higher risk of bleeding associated with DOACs vs dicumarol could be mostly explained by the worse clinical profile of patients receiving DOACs. Risk of bleeding was rather high, and warrants close clinical monitoring.

Section snippets

Study Design and Participants

We registered prospectively all patients who attended the outpatient clinic of the Geriatric Medicine Department at a tertiary hospital from January 1, 2010, to June 30, 2015. Inclusion criteria for this study were age over 74 years; evidence of AF in an electrocardiogram or 24-hour electrocardiographic recording, which was considered nonvalvular in origin according to a transthoracic echocardiography; and having started on anticoagulation in the previous 3 months. Exclusion criteria were (1)

Results

Among the 554 participants, 193 received treatment with dicumarol, 203 with dabigatran, 112 with rivaroxaban, and 46 with apixaban. Prescribed doses for DOACs were the following: (1) 110 mg twice daily in 182 (89.6%) patients and 150 mg twice daily in 21 (10.4%) patients for dabigatran; (2) 15 mg once daily in 88 (78.6%) patients and 20 mg once daily in 24 (21.4%) patients for rivaroxaban; and (3) 2.5 mg twice daily in 34 (73.9%) patients and 5 mg twice daily in 12 (26.1%) patients for apixaban.

Discussion

In very old patients with NVAF, this study shows that the higher risk of bleeding associated with DOACs vs dicumarol could be mostly due to the worse clinical profile of patients receiving DOACs. Moreover, the risk of bleeding was rather high, and warrants close clinical monitoring.

Older old and frail patients with AF receive oral anticoagulants less frequently than their younger and nonfrail counterparts. Among 207 patients with AF admitted to an acute care hospital and followed during

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    The authors declare no conflicts of interest.

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