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Use of direct oral anticoagulants in very elderly patients

a case report of apixaban in an ultracentenary patient

Manno, Girolamoa; Novo, Giuseppinaa; Corrado, Eglea; Coppola, Giuseppea; Novo, Salvatorea,b

Journal of Cardiovascular Medicine: June 2019 - Volume 20 - Issue 6 - p 403–405
doi: 10.2459/JCM.0000000000000752
Case report

aDepartment of Emergency and Urgency, Biomedic Department of Internal Medicine and Specialities (DIBIMIS)

bChair and Post/Graduate School of Cardiovascular Diseases, Department for Promoting Health (PROSAMI), Division of Cardiology, University Hospital ‘Paolo Giaccone’ of Palermo, Palermo, Italy

Correspondence to Dr Girolamo Manno, MD, Via Verona, 37 Raffadali (AG) 92015, Italy Tel: +39 3683482563; e-mail:

Received 30 August, 2018

Revised 26 November, 2018

Accepted 9 December, 2018

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Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its incidence rises steadily with each decade.1–3 AF is associated with substantial mortality and morbidity, including a five-fold increase in the risk of stroke.4–6 Stroke prevention in older AF patients is important as stroke risk rises dramatically with age.1,5 Older people with AF do better on OAC. Also, they do better on direct oral anticoagulants (DOACs) rather than on vitamin k antagonist (VKA).7–9 In this particular category of patients, balancing risks and benefits of antithrombotic strategies is crucial, because, in parallel, the bleeding risk also increases.6 Oral anticoagulation represents the cornerstone of treatment to reduce the risk of cardioembolic stroke in patients with atrial fibrillation (class of recommendation I, level of evidence A).10 Since 2010, the regulatory approval of four DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) has provided an alternative to the use of warfarin for the prevention of cardioembolic stroke in ‘non valvular atrial fibrillation’ (NVAF).6 Phase III randomized clinical trials have shown that DOACs have at least equal efficacy, with lower rates of intracranial hemorrhage compared with warfarin.11–15 Despite the availability of these safer drug alternatives to warfarin, unfortunately, oral anticoagulation use remains suboptimal in elderly patients with atrial fibrillation.6,16

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Case report

We report the case of a 104-year-old Sicilian patient (man), admitted for a routinary control, to our ambulatory, in the Cardiology Unit of the University Hospital ‘Paolo Giaccone’ in Palermo. At presentation the patient had a blood pressure of 145/60 mmHg, glycemia of 119 mg/dl, Sat. O2 95%. His CHA2DS2-VASc Score was 5 (Hypertension + 1, Age > 75 years + 2, Previous TIA +2), HAS-BLED Score 3 (Age > 75 years + 1, Previous TIA +1, Hypertension + 1). Clinical Frailty, calculated by the ‘Canadian Study of Health and Aging’ (CHSA),1 showed a value of 6 (moderately frail). The general characteristics of the patient are reported in Table 1. Regarding clinical and pharmacological history: about 15 years before, he reported surgery for cataracts and cholecystectomy. About 15 years before: TIA. The patient suffered of chronic atrial fibrillation, in the last 10 years (in treatment with apixaban 2.5 mg bid, in the last year, and bisoprolol 1.25 mg qd, for rate control), arterial hypertension (in treatment with olmesartan/amlodipina 40/10 mg qd) and benign prostatic hypertrophy (in therapy with tamsulosin 0.4 mg qdr). In addition, the patient was on furosemide 25 mg qd. The patient reported to have discontinued therapy with warfarin, since 2016, for poor INR control and for difficulty in performing periodic blood samples. For this reason the cardiologist gave therapy with apixaban 2.5 mg bid (according to age and renal function). The patient reports undergoing periodical blood tests to check renal and hepatic function, and blood count (controls at 0, 3, 6 and 12 months since starting DOAC therapy). Hepatic and renal function values, together with haemochromocytometric parameters, remained stable throughout the treatment (see Table 2). No bleeding episodes of any kind were reported, with the great advantage of a noticeable improvement in the patient's quality of life.

Table 1

Table 1

Table 2

Table 2

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Elderly NVAF patients are at increased risk of stroke and bleeding.1,17 Vitamin K antagonists have long been the only option for oral anticoagulation.18 In spite of ample evidence that Vitamin K antagonists reduce the risk of stroke and disability, anticoagulation has historically been underutilized in the very elderly population.18 An increased risk of bleeding in this patient subgroup as well as frequent falls have been commonly cited reasons to avoid anticoagulation.3 The improved safety profile of DOACs may enable treatment of elderly patients who were previously untreated, further improving on this net clinical benefit.19 In more recent years, DOACs have shown to be not-inferior to VKA in the prevention of stroke and embolism in patients with AF.11–14 The safety and efficacy data of DOACs in the elderly come from over 30,000 patients aged >75 years who were included in the pivotal trials that led to the approval of these medications. In the respective phase III randomized clinical trials both dabigatran and rivaroxaban were associated with lower major bleeding rates than warfarin among patients with atrial fibrillation aged ≥75 years.11,13 In the Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation (ARISTOTLE) study the use of apixaban was associated with less major bleeding, less total bleeding, and less intracranial hemorrhage regardless of age.12 As the risk of stroke, death, and major bleeding increased significantly with age, the absolute benefits of apixaban were greater in the older population. Data from the Effective aNticoaGulation with factor Xa next GEneration in Atrial FibrillationThrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48) trial on edoxaban in elderly and very elderly population indicate an increased net clinical benefit with the use of this drug versus warfarin.14 In a retrospective cohort study Khan et al.18 had assessed the safety of several DOACs in elderly patients (75+), managed in a healthcare system encompassing both community and academic settings. In this study, compared with warfarin, DOACs were shown to be a safe form of anticoagulation in very elderly patients with AF. Based on these data, DOACs offer a safer alternative to VKAs.18–20 In fact DOAC prescriptions have increased substantially among incident OAC users with nonvalvular AF.1–3 However, a number of factors, including frailty, the presence of multiple comorbidities, polypharmacy, high prevalence of renal dysfunction, cognitive decline and risk of falls may elicit in elderly patients concerns with DOACs that are not seen in younger patients. For this reason, in very elderly patients the choice of the NOAC should be done on an individual basis according to several features of patients.1 The peculiarity of our case is the demonstration of the safety of DOACs in very elderly patients confirming that age should not be a limiting factor in the choice of anticoagulation, but the choice must be based on the individual risk profile of the patient.

In conclusion, treatment with anticoagulants of elderly, frail patients, affected by atrial fibrillation, will be an unavoidable, very hard challenge in the future for the health systems in the world. In the past, the fear of bleeding has led, probably, to malpractice, with underuse of anticoagulation in older populations, but in recent years the introduction of DOACs may offer a safer alternative to warfarin, particularly in this setting of patients. Prospective studies involving frail, very elderly (+80) people with FA are needed to further confirm these data.

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Conflict of interest

There are no conflicts of interest.

No financial interest in this manuscript.

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