Annual Rates Of Major Bleeding Research Articles

Predictors of adverse clinical outcomes in atrial fibrillation patients with concomitant renal impairment under rivaroxaban therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and mortality, and concomitant renal impairment confers a worse prognosis. However, those factors that may limit the use of direct-acting oral anticoagulants in AF patients with renal impairment have not been further investigated, as they confer a higher risk of adverse events in this patient population. Purpose To investigate predictors of adverse clinical outcomes in AF patients with renal impairment who were treated with rivaroxaban. Methods The EMIR study is an observational, multicenter study including patients with AF treated with rivaroxaban for at least the previous 6 months. During 2.5 years of follow-up, the occurrence of thromboembolic events (the composite of isquemic stroke, transient ischemic attack, systemic embolism and myocardial infarction [MI]), major bleeding (ISTH definition) and major adverse cardiovascular events (MACE: fatal/non-fatal MI, myocardial revascularization and cardiovascular death) were recorded. For the present analysis, creatinine clearance (CrCl) was estimated by using the Cockroft-Gault equation and renal impairment was defined as a CrCl <60 mL/min. Results 1433 patients were included (44.5% female; mean age 74.2±9.7 years), of which 498 (35.1%) had CrCl <60 mL/min. The mean CHA2DS2-VASc and HAS-BLED were 3.5±1.5 and 1.6±1.0, respectively. During the follow-up, 7 (1.4%) patients with CrCl <60 mL/min suffered a thromboembolic event, 16 (3.2%) suffered major bleeding, and 19 (3.8%) suffered a MACE. Compared to patients with normal renal function, patients with CrCl <60 mL/min showed a higher annual rate of major bleeding (0.62%/year vs. 1.87%/year; p=0.003) and MACE (0.62%/year vs. 1.97%/year; p=0.002). Multivariate analyses demonstrated that the CHA2DS2-VASc score (OR 1.84; 95% CI 1.11–3.07) was associated with a higher risk of thromboembolic events; whereas the HAS-BLED score (OR 2.25; 95% CI 1.41–3.59) and any dependency level (OR 3.42; 95% CI 1.17–9.98) were associated with a higher risk of major bleeding; and male sex (OR 3.55; 95% CI 1.08–11.63) and heart failure (OR 4.67; 95% CI 1.62–13.51) with a higher risk of MACE. The use of antiplatelet agents was also independently associated with an increased risk of thromboembolic events and MACE (OR 12.28; 95% CI 2.50–60.18; and OR 8.72; 95% CI 2.86–26.59; respectively). Conclusions Rivaroxaban showed excellent results in moderate renal impairment. However, the annual rate of major bleeding and MACE was higher in AF patients with impaired renal function. In patients with AF and renal impairment, male sex, the presence of heart failure, dependency, the concomitant use of antiplatelets, and greater comorbidity according to the CHA2DS2-VASc and HAS-BLED, were associated with higher risk of adverse clinical outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer

Outcomes in VKA-treated patients with atrial fibrillation and chronic kidney disease: Clinical trials vs 'real-world'.

Our objectives were to evaluate the risk of adverse events in a 'real-world' vs 'clinical trial' cohort of atrial fibrillation (AF) patients with chronic kidney disease (CKD). We studied patient-level data for vitamin K antagonist-treated AF patients with a creatinine clearance <60mL/min from the Murcia AF Project and AMADEUS trial. The study end-points were ischaemic stroke, major bleeding, all-cause mortality, myocardial infarction and intracranial haemorrhage. This study included 1,108 AF patients with CKD. The annual rate of the composite study outcome of ischaemic stroke, major bleeding and all-cause mortality was higher in the real-world (13.4%) vs AMADEUS (6.6%) cohort with an IRR of 2.04 (95% CI,1.34-3.09), P<.001. Individual annual rates of major bleeding, all-cause mortality and non-cardiovascular mortality were significantly greater in the real-world cohort. Similar findings were demonstrated even after multivariable adjustment, with the composite outcome HR of 2.85 (95% CI,1.74-4.66), P<.001. In a propensity score matched cohort, this risk remained significantly higher in the real-world cohort (IRR 2.95 [95% CI,1.03-10.28], P=.027), as did the risk of major bleeding and all-cause mortality. Vitamin K antagonist-treated AF patients with CKD are exposed to significant annual rates of major adverse events including all-cause mortality. This risk may be under-appreciated in the idealised environment of randomised controlled trials.

Anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease and atrial fibrillation. Experience with Idarucizumab

Aim. To study the characteristics of direct oral anticoagulant-related bleeding in patients with heart failure in combination with chronic obstructive pulmonary disease (COPD) and atrial fibrillation. To show the efficacy of idarucizumab in complex therapy of severe gastrointestinal bleeding caused by dabigatran. Material and methods. The single-center prospective observational study included 150 patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants. Of these patients, 75 had heart failure in combination with COPD (experimental group) and 75 — HF without comorbidities (comparison group). Groups were formed by propensity score matching. Sex, age, bleeding risk by HAS-BLED score were covariates. HF was diagnosed in accordance with the criteria applied by Russian Federal clinical guidelines. COPD was diagnosed according to GOLD 2011-2020 criteria. Frequency of all bleeding, major bleeding, bleeding into critical organs were evaluated. Follow-up period was 14 (12; 16) months. Cox regression method was used to determine relationships. Results. Annual rate of major bleeding in group of HF and COPD was higher (Hazard ratio (HR) 3,0, 95% confidence interval (CI) 1,1-6,2, р =0,02), regardless of which anticoagulant was used. Gastrointestinal bleeding occurs in 7 (9,3%) and 2 (2,7%) patients (HR 3,5, 95% CI 1,1-7,3, р =0,05). In subjects with comorbidity, major and gastrointestinal bleeding were associated with partial pressure of arterial oxygen (HR 0,89, 95% CI 0,55-0,95 and HR 0,88, 95% CI 0,50-0,98 respectively), serum NT-pro-BNP (HR 1,10, 95% CI 1,05-2,14 and HR 1,14, 95% CI 0,07-4,28, respectively) and chemokine ligand 18 (HR 1,15, 95% CI 1,11-5,75 and HR 1,13, 95% CI 1,09-4,50). A case of successful use of idarucizumab for reversal of dabigatran anticoagulant effect in the patient with severe bleeding from esophageal erosion, nonvalvular AF, HF and COPD was reported. Coagulation was restored within 4 hours, which allowed to stop bleeding conservatively and antishock measures were effective. Conclusion. Anticoagulation therapy in patients with AF and comorbidity of HF and COPD is associated with additional risk of major bleeding, especially gastrointestinal. Possibility to reverse the anticoagulant effect is an important argument when choosing an anticoagulant for these patients.

P999Major adverse events with percutaneous left atrial appendage closure in patients with atrial fibrillation in real life setting

Abstract Transcatheter left atrial appendage (LAA) closure is an alternative strategy for stroke prevention in atrial fibrillation (AF) patients with an inacceptable risk of bleeding with oral anticoagulation (OAC). A better characterization of major adverse clinical events after LAA closure in daily practice is still needed. Methods We analysed data from all AF patients treated with Watchman or Amplatzer LAA closure according to European guidelines in 8 French cardiology departments. Antithrombotic management was decided for each patient on an individual basis. A Cox regression model was used for multivariable analysis of major adverse events. Yearly rate of ischemic stroke during follow-up was calculated and compared to that expected for a same risk score population. Yearly rate of bleeding was extrapolated from that reported with the HASBLED score. Results A total of 469 consecutive AF patients (299 males, 74.9±8.9 years old, mean CHA2DS2-VASc score 4.5±1.4, HASBLED score 3.7±1.0) received LAA closure from March 2012 to January 2017. There were 272 Watchman devices (58%) and 197 ACP devices (42%) implanted. At discharge, 36% received a single anti platelet therapy (APT), 23% received dual APT, 29% received OAC and no APT, 5% received OAC plus APT and 8% received no antithrombotic therapy. Mean follow up was 11.4 months (median 7, interquartile 3–22 months) during which 70 major adverse events (19 ischemic strokes, 18 major haemorrhages and 33 deaths) were recorded in 69 patients. The annual rate of ischemic stroke was 3.96%, which translates into a 13% relative risk reduction (95% CI −59 to 52%) as compared with the calculated stroke rate for similar CHA2DS2-VASc score after adjustment for exposure to APT and OAC. The annual rate of major bleeding in the study was 3.75%, which corresponds to a 48% relative risk reduction (95% CI 9 to 70%) as compared with the rate that would have been expected based on a comparable HAS-BLED score. Yearly rate of mortality was 7.4% (2.5 to 3 fold higher than in previous randomized trials) and the rate of non-cardiovascular death was 82%. None of the baseline characteristics was predictive of major adverse events, neither in univariate nor in multivariable analysis, which highlights the difficulty in identifying a risk of unfavourable outcome with simple tools. Conclusions AF patients treated with LAA closure may have a lower risk of stroke and bleeding events compared to their theoretical risk. However, our findings indicate that a high rate of major adverse events is observed in these patients during follow-up. This questions the suggested cost-effectiveness of the procedure (with models based on previous trials) for a real-life perspective. A better identification of patients with a relevant benefit of LAA closure is needed among those with long-term anticoagulation contraindication, both for an optimal management of each patient on an individual basis and for a global perspective with limited healthcare resources.

Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage

Percutaneous left atrial appendage closure (LAAC) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation. This study aimed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage (ICH). In this explorative, prospective, single-center study, consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores, respectively. Single antiplatelet therapy was given for at least 6 months post implantation. Clinical follow-up included cardiological evaluations at 1, 3, 6, and 12 months, and neurological evaluations at 3 and 12 months. A total of 46 patients underwent LAAC with a mean follow-up of 12 ± 7 months. The observed annual rate of ischemic stroke was 4.35% compared with an expected rate of 7.23% according to the mean risk of the population based on CHA2DS2-VASc score, which translated into a 40% risk reduction. The observed annual rate of major bleeding was 4.35% compared with an expected rate of 8.05% according to the mean risk of the population based on HAS-BLED score, which translated into a 46% risk reduction. LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH, with an acceptable periprocedural risk. Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants.

Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug.

To investigate the safety, feasibility, and efficacy of left atrial appendage occlusion (LAAO) with the AMPLATZER Cardiac Plug (ACP) for stroke prevention in patients with atrial fibrillation (AF). Data from consecutive patients treated in 22 centres were collected. A total of 1,047 patients were included in the study. Procedural success was 97.3%. There were 52 (4.97%) periprocedural major adverse events. Follow-up was complete in 1,001/1,019 (98.2%) of successfully implanted patients (average 13 months, total 1,349 patient-years). One-year all-cause mortality was 4.2%. No death at follow-up was reported as device-related. There were nine strokes (0.9%) and nine transient ischaemic attacks (0.9%) during follow-up. The annual rate of systemic thromboembolism was 2.3% (31/1,349 patient-years), which is a 59% risk reduction. There were 15 major bleedings (1.5%) during follow-up. The annual rate of major bleeding was 2.1% (28/1,349 patient-years), which is a 61% risk reduction. Patients with single LAAO on aspirin monotherapy or no therapy and longer follow-up had fewer cerebral and fewer bleeding events. In this multicentre study, LAAO with the ACP showed high procedural success and a favourable outcome for the prevention of AF-related thromboembolism. Modification in antithrombotic therapy after LAAO may result in reduction of bleeding events.

Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE‐LY trial

We evaluated the effects of dabigatran compared with warfarin in the subgroup of patients with previous symptomatic heart failure (HF) in the RE-LY trial. RE-LY compared two fixed and blinded doses of dabigatran (110 and 150 mg twice daily) with open-label warfarin in 18 113 patients with AF at increased risk for stroke. Among 4904 patients with HF, annual rates of stroke or systemic embolism (SE) were 1.92% for patients on warfarin compared with 1.90% for dabigatran 110 mg [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.69-1.42] and 1.44% for dabigatran 150 mg (HR 0.75, 95% CI 0.51-1.10). Annual rates of major bleeding were 3.90% for the group on warfarin, compared with 3.26% for dabigatran 110 mg (HR 0.83, 95% CI 0.64-1.09) and 3.10% for dabigatran 150 mg (HR 0.79, 95% CI 0.60-1.03). Rates of intracranial bleeding were significantly lower for both dabigatran dosages compared with warfarin in patients with HF (dabigatran 110 mg vs. warfarin, HR 0.34, 95% CI 0.14-0.80; dabigatran 150 mg vs. warfarin, HR 0.39, 95% CI 0.17-0.89). The relative effects of dabigatran vs. warfarin on the occurrence of stroke or SE and major bleeding were consistent among those with and without HF and those with low (≤40%) or preserved (>40%) LVEF (P interaction not significant). The overall benefits of dabigatran for stroke/SE prevention, and major and intracranial bleeding, relative to warfarin in the RE-LY trial were consistent in patients with and without HF.

Aspirin versus warfarin in atrial fibrillation: decision analysis may help patients’ choice

the primary prevention of ischaemic stroke in chronic non-valvular atrial fibrillation (AF) typically involves consideration of aspirin or warfarin. CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5-1.2% per year. given a 'warfarin, aspirin or no therapy' choice, AF patients will prefer the option that maximises the annual probability of not having a stroke and not having a major bleed. decision tree applied to the 60 possible combinations of CHA(2)DS(2)-VASc and HAS-BLED scores. according to the pre-specified hypothesis, when CHA(2)DS(2)-VASc is <2, the balance of risk and benefit would advise no treatment; when CHA(2)DS(2)-VASc is 2 or 3, warfarin would be best when HAS-BLED <2, otherwise no treatment would be advised; for CHA(2)DS(2)-VASc =4, warfarin would be best when HAS-BLED <3, otherwise no treatment would be advised and for CHA(2)DS(2)-VASc ≥5, warfarin would be the preferred option if HAS-BLED <4, otherwise aspirin would be advised. this theoretical exercise illustrates the potential benefit of decision analysis in an area where high complexity and uncertainty still remain.

Drug Betters Aspirin for Stroke of A Fib

Drug Betters Aspirin for Stroke of A Fib