Major Bleeding In Elderly Patients Research Articles

Growth Differentiation Factor-15 Based ABC (Age, Biomarkers, Clinical History)-AF (Atrial Fibrillation)-Bleeding Risk Score for Elderly Patients with Nonvalvular Atrial Fibrillation.

Background Growth differentiation factor-15 (GDF-15) is a strong predictor of bleeding in atrial fibrillation (AF) patients. The novel ABC (age, biomarkers, and clinical history), AF, and bleeding risk score outperforms HAS-BLED bleeding risk score for major bleeding (MB) in patients with AF receiving oral anti-coagulation in the clinical trial cohort. However, it has not been entirely externally validated. We aimed to refine and understand the application of the ABC-AF bleeding risk score in elderly (aged ≥65 years old) patients with nonvalvular atrial fibrillation (NVAF) for predicting the different types of bleeding events and anti-thrombotic treatments. Methods We identified elderly patients with NVAF between March 2018 and December 2019 who were hospitalized for the first time after a diagnosis of NVAF. We measured the plasma concentration of the ABC biomarkers (growth differentiation factor 15 (GDF-15) and cardiac troponin-T (cTnT)) from enrolled patients. We collected their general information and follow up for one year until December 2020. During the follow-up period, information on the occurrence of bleeding events (major bleeding, clinically relevant nonmajor gastrointestinal bleeding (CRNM GIB), and minor bleeding events) was collected. Results We enrolled 342 elderly NAVF patients; the ABC-AF bleeding and HAS-BLED scores were quantified. With an average of 1.5 years of follow-up, 6 patients had an intracranial hemorrhage; 57 patients had CRNM GIB; and 68 patients had minor bleeding events (36 fecal occult blood positive and 32 other minor bleeding events). The ABC-AF bleeding score yielded a C-index of 0.72 (95% CI 0.60–0.84) for predicting MB in elderly patients with NAVF, C-index of 0.69 (95% CI 0.57–0.82) by HAS-BLED score. Comparison of the incidence of bleeding events during follow-up and the predicted 1-year incidence of bleeding events by each bleeding risk score, ABC-AF bleeding, and HAS-BLED scores have similar value in predicting the risk for elderly patients with NAVF in different types of bleeding events, whether on oral anti-coagulation treatment (OAC) or non-OAC (P > 0.05). Conclusion In elderly patients with NVAF, the biomarker-based ABC-AF bleeding score showed similar performance compared with the HAS-BLED bleeding risk score.

Cost-Effectiveness Analysis of Direct Oral Anticoagulants Vs. Vitamin K Antagonists in the Elderly With Atrial Fibrillation: Insights From the Evidence in a Real-World Setting.

Background: In the clinical setting, the economic benefits of direct oral anticoagulants (DOACs) in elderly patients with atrial fibrillation (AF) remain unclear. This study aimed to estimate and compare the cost-effectiveness of DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) and vitamin K antagonists (VKAs; warfarin) in preventing stroke among AF patients aged >75 years in real-world practice.Methods: A Markov model with a 10-year span was constructed to estimate the long-term clinical and economic outcomes among AF patients aged >75 years treated with DOACs and warfarin. The study was populated with a hypothetical cohort of 10,000 AF patients aged >75 years. Probabilities of clinical outcomes were obtained from the pooled observational studies (OSs), comparing DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) with VKAs. Other model inputs, including the utilities and the costs, were all estimated from public sources and the published literature. The costs, quality-adjusted life-years (QAYLs), and incremental cost-effectiveness ratios (ICER) were estimated for each treatment strategy. Subgroup analyses of individual DOACs and the scenario analysis were performed. Uncertainty was evaluated by deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA).Results: Compared to warfarin, DOACs were associated with a gain of 0.36 QALY at an additional cost of $15,234.65, resulting in an ICER of $42,318.47 per QALY. Sensitivity analysis revealed that the ICER was sensitive to the cost of DOACs. Direct oral anticoagulants also shifted from dominating to dominated status When their annual costs of DOACs were over $3,802.84 or the risk ratio of death compared to warfarin was over 1.077%/year. Probabilistic sensitivity analysis (PSA) suggested that DOACs had a 53.83 and 90.7% probability of being cost-effective when the willingness-to-pay threshold was set at $50,000 and $100,000, respectively. Among all the four individual DOACs, edoxaban treatment was revealed as the preferred treatment strategy for the AF patients aged over 75 years by yielding the most significant health gain with the relatively low total cost.Conclusions: Despite the high risk for major bleeding in elderly patients with AF, DOACs are more cost-effective treatment options than warfarin in real-world practice. Edoxaban was the preferred treatment strategy among four kinds of DOACs for AF patients aged over 75 years. Furthermore, beyond their safety profiles, the treatment benefits of DOACs assumed greater relevance and importance in older adults.

Predicting the risk for major bleeding in elderly patients with venous thromboembolism using the Charlson index. Findings from the RIETE.

Old patients receiving anticoagulant therapy for venous thromboembolism (VTE) are at an increased risk for bleeding. We used data from the RIETE registry to assess the prognostic ability of the Comorbidity Charlson Index (CCI) to predict the risk for major bleeding in patients aged > 75years receiving anticoagulation for VTE beyond the third month. We calculated the area under the receiver-operating characteristic curve (AUC), the category-based net reclassification index (NRI) and the net benefit (NB). We included 4303 patients with a median follow-up of 706days (interquartile range [IQR] 462-1101). Of these, 147 (3%) developed major bleeding (27 died of bleeding). The AUC was 0.569 (95% CI 0.524-0.614). Patients with CCI ≤ 4 points were at a lower risk for adverse outcomes than those with CCI > 10 (major bleeding 0.81 (95% CI 0.53-1.19) vs. 2.21 (95% CI 1.18-3.79) per 100 patient-years; p < 0.05; all-cause death 1.9 (95% CI 1.45-2.44) vs. 15.67 (95% CI 12.63-19.22) per 100 patient-years; p < 0.05). A cut-off point of 4 points (CCI4) had a sensitivity of 82% (95% CI 75-89) and a specificity of 30% (95% CI 29-31) to predict major bleeding beyond the third month. CCI4 reclassification improved the NB of the RIETE bleeding score to predict bleeding beyond the third month (CCI4 NB 1.78% vs. RIETE NB 0.44%). Although the AUC of the CCI to predict major bleeding was modest, it could become an additional help to select patients aged > 75years that obtain more benefit of extended anticoagulation, due to a lower risk for bleeding and better survival.

Risk of major bleeding in elderly patients with atrial fibrillation on direct oral anticoagulants: real world experience.

Background The efficacy and safety of direct oral anticoagulants is well established in patients with atrial fibrillation. However, data on their use in the oldest old patients (≥ 85years), who have the highest risk of bleeding, is scarce. Objective The aim of this study was to evaluate the safety of direct oral anticoagulants in the oldest old patients with atrial fibrillation and assess the impact of age on major bleeding events. Setting Anticoagulation Clinic of the Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia. Methods From our single-centre prospective registry we enrolled 2260 consecutive atrial fibrillation patients aged ≥ 65years that were started on dabigatran, rivaroxaban or apixaban. The mean duration of treatment exposure was 735days. The primary outcome was the incidence of major bleeding. The incidence of thromboembolic events and death were also assessed. Potential risk factors for major bleeding were evaluated using Cox regression analysis. Main outcome measure Rate of major bleeding. Results During the follow-up 106 patients experienced major bleeding (2.3%/year). The oldest old patients (≥ 85years) had the highest risk of any major bleeding (HR 2.50, 95% CI 1.44-4.32, p = 0.001), intracranial bleeding (HR 4.74, 95% CI 1.48-15.14, p < 0.01) and major gastrointestinal bleeding (HR 2.32, 95% CI 1.10-4.89, p < 0.03) compared to the group of patients aged 65-74years, even though the majority of them were treated with reduced doses of direct oral anticoagulants. Significant predictors for major bleeding were age group ≥ 85years (HR 2.52, 95% CI 1.43-4.47, p = 0.001) and history of bleeding (HR 3.32, 95% CI 1.87-5.90, p < 0.001). The incidence of a composite of stroke, transient ischemic attack and systemic embolism was 1.3%/year. Conclusion In this prospective real-world clinical study we have shown that the oldest old patients have the highest risk of major bleeding, which is further increased with a patient's history of bleeding.

Revascularisation compared with initial medical therapy for non-ST-elevation acute coronary syndromes in the elderly: a meta-analysis

ObjectiveWhether revascularisation is superior to medical therapy in older populations presenting with non-ST-elevation acute coronary syndromes (NSTEACS) remains contentious, with inconclusive evidence from randomised trials. We aimed to compare routine...

Frailty predicts major bleeding within 30 days in elderly patients with Acute Coronary Syndrome

ObjectiveBleeding in ACS patients is an independent marker of adverse outcomes. Its prognostic impact is even worse in elderly population. Current bleeding risk scores include chronological age but do not consider biologic vulnerability. No studies have assessed the effect of frailty on major bleeding. The aim of this study is to determine whether frailty status increases bleeding risk in patients with ACS. MethodsThis prospective and observational study included patients aged ≥75years admitted due to type 1 myocardial infarction. Exclusion criteria were severe cognitive impairment, impossibility to measure handgrip strength, cardiogenic shock and limited life expectancy due to oncologic diseases. The primary endpoint was 30-day major bleeding defined as a decrease of ≥3g/dl of haemoglobin or need of transfusion. ResultsA total of 190 patients were included. Frail patients (72, 37.9%) were older, with higher comorbidity features and with a higher CRUSADE score at admission. On univariate analysis, frailty predicted major bleeding during 30-day follow-up despite less frequent use of a P2Y12 inhibitor (66.2% vs 83.6%, p=0.007) and decreased catheterisation rate (69.4% vs 94.1%, p<0.001). Major bleeding was associated with increased all-cause mortality at day 30 (18.2% vs 2.5%, p<0.001). On multivariate analysis, frailty was an independent predictor for major bleeding. ConclusionFrailty phenotype, as a marker of biological vulnerability, is an independent predictor of major bleeding in elderly patients with ACS. Frailty can play an important role in bleeding risk stratification and objective indices should be integrated into routine initial evaluation of these patients.

Physical Activity and Risk of Bleeding in Elderly Patients Taking Anticoagulants

A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Physical activity and risk of bleeding in elderly patients taking anticoagulants

Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. In a prospective multicenter cohort study of 988 patients aged ≥65years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. During a mean follow-up of 22months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Impact of advanced age on the safety and effectiveness of paclitaxel‐eluting stent implantation in patients with ST‐segment elevation myocardial infarction undergoing primary angioplasty

To assess the impact of age on safety and efficacy of paclitaxel-eluting stent (PES) implantation during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). The benefits of paclitaxel-eluting stent (PES) implantation during primary PCI were confirmed by the long-term results of the HORIZONS-AMI trial. Whether the effects of PES are independent of age has not been reported. Data on 3,006 patients from the HORIZONS-AMI study randomized in a 3:1 ratio to PES or bare-metal stent (BMS) in whom at least one stent was implanted were assessed. There were 2,302 (76.6%) patients <70, and 704 patients ≥70 years of age. At 3 years, among older patients a trend toward lower risk of major adverse cardiac events (MACE; death from any cause, stroke, reinfarction and unplanned revascularization for ischemia) related to PES use was observed (PES vs. BMS: 18.0% vs. 21.3%; P = 0.07). There was also a trend for reduction of MACE related to PES in older patients (26.4% vs. 33.1%; P = 0.09). Both, patients <70 and ≥70 years of age treated with PES were at lower risk for ischemic target vessel revascularization. However, a higher risk of major bleeding in elderly patients treated with PES was observed (P = 0.02 for interaction between age group and PES effects). No interaction between age and stent type in terms of the risk of other clinical end points, including all-cause death, was confirmed. For STEMI patients undergoing primary PCI, the implantation of PES as compared with BMS reduced ischemic TVR, and this effect was independent of age.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism

The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE. In a prospective multicenter Swiss cohort study, we studied 663 patients aged ≥ 65 years with acute VTE. The outcome was a first major bleeding at 90 days. We classified patients into three categories of bleeding risk (low, intermediate and high) according to each score and dichotomized patients as high vs. low or intermediate risk. We calculated the area under the receiver-operating characteristic (ROC) curve, positive predictive values and likelihood ratios for each score. Overall, 28 out of 663 patients (4.2%, 95% confidence interval [CI] 2.8-6.0%) had a first major bleeding within 90 days. According to different scores, the rate of major bleeding varied from 1.9% to 2.1% in low-risk, from 4.2% to 5.0% in intermediate-risk and from 3.1% to 6.6% in high-risk patients. The discriminative power of the scores was poor to moderate, with areas under the ROC curve ranging from 0.49 to 0.60 (P = 0.21). The positive predictive values and positive likelihood ratios were low and varied from 3.1% to 6.6% and from 0.72 to 1.59, respectively. In elderly patients with VTE, existing bleeding risk scores do not have sufficient accuracy and power to discriminate between patients with VTE who are at a high risk of short-term major bleeding and those who are not.

Impact of the transradial approach in the occurrence of major bleeding in elderly patients undergoing percutaneous coronary intervention

ABSTRACT Background The occurrence of major bleeding after percutaneous coronary intervention (PCI) is associated to higher morbidity and mortality, and advanced age is one of its main predictors. The aim of this analysis was to evaluate the impact of the use of the transradial approach in the incidence of bleeding complications in elderly patients undergoing PCI. Methods Consecutive and controlled registry including patients over 60 years of age undergoing PCI by transradial approach. Angiographic procedure success, technical failure, and the incidence of ischemic adverse events and major bleeding were evaluated. Results Between May 2008 and December 2010, 707 elderly patients underwent PCI, of whom 635 (89.8%) used the transradial approach. Mean age was 69.9 ± 7.2 years, 11.5% were > 80 years of age, 39.7% were female and 30.9% had diabetes mellitus. Acute ischemic syndrome accounted for 72% of clinical indications. The angiographic success rate was 96.8% with a crossover rate of 2.8%. The in-hospital mortality rate was 2.4%, myocardial infarction occurred in 0.9%, stroke in 0.3% and stent thrombosis in 0.9%. Hematomas were reported in 1.6% of procedures, with a major bleeding rate of 0.8%. Conclusions In elderly patients undergoing PCI, representing the real-world practice and at a high risk for bleeding, the use of the transradial approach was associated with a low major bleeding rate.

Impact of the transradial approach in the occurrence of major bleeding in elderly patients undergoing percutaneous coronary intervention

The occurrence of major bleeding after percutaneous coronary intervention (PCI) is associated to higher morbidity and mortality, and advanced age is one of its main predictors. The aim of this analysis was to evaluate the impact of the use of the transradial approach in the incidence of bleeding complications in elderly patients undergoing PCI. Consecutive and controlled registry including patients over 60 years of age undergoing PCI by transradial approach. Angiographic procedure success, technical failure, and the incidence of ischemic adverse events and major bleeding were evaluated. Between May 2008 and December 2010, 707 elderly patients underwent PCI, of whom 635 (89.8%) used the transradial approach. Mean age was 69.9 ± 7.2 years, 11.5% were > 80 years of age, 39.7% were female and 30.9% had diabetes mellitus. Acute ischemic syndrome accounted for 72% of clinical indications. The angiographic success rate was 96.8% with a crossover rate of 2.8%. The in-hospital mortality rate was 2.4%, myocardial infarction occurred in 0.9%, stroke in 0.3% and stent thrombosis in 0.9%. Hematomas were reported in 1.6% of procedures, with a major bleeding rate of 0.8%. In elderly patients undergoing PCI, representing the real-world practice and at a high risk for bleeding, the use of the transradial approach was associated with a low major bleeding rate. Impacto da Utilização do Acesso Radial na Ocorrência de Sangramento Grave entre Idosos Submetidos a Intervenção Coronária Percutânea A ocorrência de sangramento grave após intervenção coronária percutânea (ICP) sabidamente associa-se a maior morbidade e mortalidade, sendo a idade avançada um de seus principais preditores. O objetivo da presente análise foi avaliar o impacto da utilização do acesso radial na incidência de complicações hemorrágicas entre idosos submetidos a ICP. Registro consecutivo, controlado, envolvendo pacientes com idade ≥ 60 anos submetidos a ICP pelo acesso radial. Avaliou-se o sucesso angiográfico do procedimento, a falência da técnica, e a taxa de eventos adversos isquêmicos e de sangramento grave. Entre maio de 2008 e dezembro de 2010, 707 pacientes idosos foram submetidos a ICP, dos quais 635 (89,8%) por meio de acesso radial. A média de idade foi de 69,9 ± 7,2 anos, 11,5% tinham idade > 80 anos, 39,7% eram do sexo feminino e 30,9%, portadores de diabetes melito. Síndrome isquêmica aguda respondeu por 72% das indicações clínicas. A taxa de sucesso angiográfico foi de 96,8%, sendo necessária a troca da via de acesso em 2,8% dos casos. A mortalidade hospitalar situou-se em 2,4%, infarto agudo do miocárdio em 0,9%, acidente vascular encefálico em 0,3% e trombose do stent em 0,9%. Hematomas foram reportados em 1,6% dos procedimentos, sendo de 0,8% a taxa de sangramento grave. Entre pacientes idosos submetidos a ICP, representativos da prática contemporânea e de elevado risco para sangramento, o uso do acesso radial associou-se a baixa incidência de sangramento grave.

Lower versus standard intensity oral anticoagulant therapy (OAT) in elderly warfarin-experienced patients with non-valvular atrial fibrillation

It has been observed that elderly patients with nonvalvular atrial fibrillation (NVAF) benefit from standard [an international normalised ratio (INR) goal of 2.0-3.0] oral anticoagulant treatment (OAT). The hypothesis that lower-intensity anticoagulation therapy can offset the higher bleeding risk in this population has never been tested in an 'ad hoc' clinical trial. Patients over 75 years of age with NVAF were randomised to receive warfarin to maintain the INR at 1.8 (range 1.5-2.0) or at a standard target of 2.5 (range 2.0-3.0). There were 135 patients in the low-intensity and 132 in the standard-intensity groups. During a mean follow-up lasting 5.1 years, 59 primary outcome events (thromboembolism and major haemorrhage) were recorded, 24 (3.5 per 100 patient-years) in the low-intensity group and 35 (5.0 per 100 patient-years) in the standard-intensity group (HR=0.7, 95% CI 0.4-1.1, p=0.1). The reduction in the primary endpoint was mainly due to a diminution in major bleedings (1.9 vs. 3.0 per 100 patient-years; HR=0.6, 95% CI 0.3-1.2, p=0.1). The median achieved INR value was 1.86 in the low-intensity and 2.24 in the standard-intensity group (p<0.001). The frequency of INR testing was 26.1 +/- 13.5 vs. 24.3 +/- 11.6 days, p<0.0001). In this exploratory study we observed a low rate of stroke and major bleeding in elderly patients (>75) being managed in an anticoagulation clinic for primary stroke prevention with low-intensity anticoagulation (INR 1.5-2.0). However, further trials are needed to confirm the hypothesis generated by the present study.

Safety of treatment with oral anticoagulants in the elderly. A systematic review.

Oral anticoagulants have documented efficacy for many indications and are widely used in elderly patients. However, there is concern about whether this treatment induces an excess of major bleeding in elderly patients. In this systematic review, the incidence of oral anticoagulant-related major bleeding among elderly patients was determined. A total of 58 reports were identified that evaluated an oral anticoagulant, included patients with a mean age of at least 60 years, and provided data on the occurrence of major bleeding or provided separate data on the occurrence of major bleeding in elderly versus younger patients. In 50 studies no age differentiation was given. Although the incidence of bleeding complications varied, a trend towards increased bleeding with increasing age was shown in patients with major orthopaedic surgery and cardiac diseases. In the 8 articles that provided separate data on the occurrence of bleeding in different age categories, there was a clear tendency towards a 2-fold increase in bleeding in elderly patients. These findings emphasise the need for caution in the use of oral anticoagulants in elderly patients. However, the decision to start oral anticoagulant treatment should be based on an evaluation of the risk/benefit balance on a careful patient-by-patient basis. In general, if oral anticoagulant treatment is started, the lowest possible effective International Normalised Ratios (INR) should be selected and regular monitoring should be done to avoid over-anticoagulation.