Risk of bleeding in very old atrial fibrillation patients on warfarin: Relationship with ageing and CHADS2 score

Abstract

Aims: In atrial fibrillation (AF) patients, age z75 years is one of the major risk factors for stroke. However, it is not clear if an upper limit for the indication to OAT exists. Methods and results: For this reason, we performed a prospective study on 290 AF patients on OAT aged z75 years (median age 82 years, total follow-up period 814 pt/ years) followed by our Anticoagulation Clinic. Seventeen major bleeding events were recorded (rate 2.1 × 100 pt/years), 11 of which cerebral (1.35 × 100 pt/years). The occurrence of major bleedings was associated with history of previous TIA or stroke [OR 3.4 (1.1-12.5), p = 0.01] and with diabetes .7) p = 0.01]. We found a trend to a progressive increase in the rate of bleeding risk with the increase of the CHADS 2 score: patients with score 4-6 showed a rate of 3.4 × 100 pt/years with respect to 1.5 × 100 pt/years of patients with lower score. Number Needed to Harm (NNH) was calculated in relation to different classes of age (75-89, 80-84, z85 years) and to CHADS 2 score. For patients in CHADS 2 score 1-3 NNH remained stable across the different age classes. Instead for patients in CHADS 2 score 4-6, NNH varied among the 3 groups of ages, reaching a value of 10 in patients ≥ 85 years. Conclusion: Our data suggest that: 1) in AF patients older than 75 years with CHADS 2 score 1-3 the risk of bleeding is low, 2) in AF patients N85 years with CHADS 2 4-6 the risk of bleeding is high so that the use of OAT should be highly individualised.

Oral Anticoagulation in Nonvalvular Atrial Fibrillation in Clinical Practice: Impact of CHADS₂ Score on Outcome

“…Recent publications [6,7] emphasize bleeding risk in anticoagulated patients with NVAF and high CHADS 2 scores. This raises the question of whether the benefit of OAC is cancelled out by an increase in adverse effects in subgroups with a worse risk profile, as reported in the SPAF II study [12].…”

“…Recent publications have indicated that higher CHADS 2 scores also predict severe bleeding [6,7] in patients receiving oral anticoagulation (OAC). Our aim was to analyze the benefits and risks of OAC in patients with NVAF in daily clinical practice according to embolic risk estimated by means of the CHADS 2 score.…”

Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation

“…Apart from renal dysfunction, higher age is an established risk factor for major bleeding events in AF. 9,17,20 Age is incorporated in all creatinine-based eGFR equations; however, even when cystatin C is used to estimate GFR, with no need to include age in the equation, the result concerning an increase in major bleeding with deteriorating renal function remains. An evaluation of both age and renal function appears reasonable when one assesses major bleeding risk in patients with AF who are undergoing oral anticoagulation.…”

Influence of Common and Rare Genetic Variation on Warfarin Dose Among African–Americans and European–Americans Using the Exome Array

“…However, warfarin therapy is challenging due to the great interpatient variability in dose requirements. Further, its narrow therapeutic index contributes to a high rate of adverse effects [7][8][9][10][11][12][13], earning warfarin a consistent ranking among the top ten drugs associated with serious adverse events [14,15]. Achieving therapeutic anticoagulation rapidly and predictably is critical for safe and effective therapy.…”

“…SNPs in CYP2C9, CYP4F2 and VKORC1 account for a greater proportion of dose variability among EAs (35-40%) than in AAs (7-10%) [23]. To dentify the influence of common SNPs on warfarin dose in AAs, the Influence of common and rare genetic variation on warfarin dose among African-Americans and European-Americans using the exome array 1060 Pharmacogenomics (2017) 18 (11) future science group Research Article Liu, Irvin, Zhi et al International Warfarin Pharmacogenetics Consortium has published a GWAS analysis of warfarin dose representing data on approximately 1000 AA adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin [25]. After conditioning their models on VKORC1 −1639G>A, CYP2C9*2 and CYP2C9*3, they identified rs12777823 within the CYP2C gene cluster on chromosome 10 as being significantly associated with warfarin dose.…”