Direct oral anticoagulant use and the incidence of bleeding in the very elderly with atrial fibrillation

Abstract

Atrial fibrillation (AF) is a major risk factor for stroke in the elderly population. The use of anticoagulation in patients with AF greatly reduces the risk for stroke, but results in an increased risk of bleeding. Over the past several years, direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, and apixaban) have been used in place of warfarin for stroke prevention in AF. We conducted a retrospective cohort study to assess the safety of DOACs in very elderly patients (75+) managed in a health care system encompassing both community and academic settings. We found that 36% of patients had moderate to severe renal failure (estimated glomerular filtration rate <59 ml/min/1.73m2) at the time of DOAC initiation. 142 patients were followed for a mean of 2.56 years, and five experienced a major bleeding episode while on anticoagulation, for a rate of 1.37 per 100 person years. All major bleeding episodes were associated with a decline in GFR compared to baseline. There were 12 non-major bleeding episodes reported. HAS-BLED scores were similar for those patients who experienced bleeding complications compared to those who did not. 21% of patients were prescribed an inappropriately low dose of DOAC based on approved recommendations. DOACS appear to be a safe form of anticoagulation in very elderly patients with AF. However, the decline in GFR among patients with major bleeding highlights the importance of routine renal function monitoring.

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

“…However, this was not limited to rivaroxaban, but also to the other DOACs as will be discussed in subsequent sections. Indeed, in a study with 140 elderly patients taking DOACs, 21 patients (15%) were on an ILD of rivaroxaban (7 patients with 10‐mg dose and 14 patients with 15‐mg dose) …”

“…Renal function dose adjustment has already proven to be a focal point. In a real‐world study with 142 patients, all the 5 observed major bleeding episodes were associated with a decline in renal function compared to baseline . Andreu Cayuelas et al also suggest that improvement in monitoring of kidney function in those undergoing therapy with DOAC would be expected to reduce risk for major haemorrhage while also protecting patients from excessive risk for thromboembolism.…”

“…5,6 However, there is concern about the extrapolation of randomized clinical trials to real-life patients 7 since the reality observed in the idealized clinical trial setting is different from the real clinical practice, where patient characteristics and outcomes differ amongst distinct trials. 8 In fact, although fixed doses of DOACs are defined in the guidelines, dose adjustments are currently recommended in the presence of specific clinical conditions, including renal function, [9][10][11][12][13] age and body weight, 14,15 increased bleeding risk (e.g. gastritis, oesophagitis, gastroesophageal reflux) 16 and concomitantly administration with other drugs that compromise DOACs systemic exposition and pharmacological effects (e.g.…”

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation

“…A recent retrospective study (n=142) assessed the safety of NOACs in elderly patients (age ≥75) [14]. Over a mean of 2.6 years, the incidence of major bleeding was low (1.37 per 100 person years) and this complication was associated with a decline in estimated creatinine clearance (eCrCl) compared to baseline.…”

Current challenges and future prospects in oral anticoagulant therapy

“…Therefore, extrapolating data from clinical trials to such patients requires a degree of caution. Studies report that the lower doses of DOACs are frequently instituted without fulfilling the recommended dose‐reduction criteria (Barra et al , ; Khan et al , ) and there is a valid concern of ‘under‐dosing’. Of note also, is the small proportion of patients in ARISTOTLE who received the lower dose of apixaban – just 4·7% (Granger et al , ).…”