Sophie Taillandier

Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: the Loire Valley Atrial Fibrillation Project

Heart failure (HF) increases the risk of stroke and thrombo‐embolism (TE) in non‐valvular atrial fibrillation (NVAF), and is incorporated in stroke risk stratification scores. We aimed to establish the role of ejection fraction (EF) in risk prediction in patients with NVAF and HF.

Renal impairment and ischemic stroke risk assessment in patients with atrial fibrillation: the Loire Valley Atrial Fibrillation Project.

OBJECTIVES This study sought to determine the risk of ischemic stroke (IS)/thromboembolism (TE) associated with renal impairment and its incremental predictive value over established risk stratification scores (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke [CHADS2] and congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke, vascular disease, age 65 to 74 years, sex category (female) [CHA₂DS₂-VASc]) in patients with atrial fibrillation (AF). BACKGROUND Risk stratification schemes for prediction of IS/TE in patients with AF are validated but do not include renal impairment. METHODS Patients diagnosed with nonvalvular AF and available estimated glomerular filtration rate (eGFR) data in a 4-hospital institution between 2000 and 2010 were identified. The study population was stratified by renal impairment defined by serum creatinine level and by eGFR measured at time of diagnosis of AF. Independent risk factors of IS/TE (including renal impairment) were investigated in Cox regression models. The incremental predictive value of renal impairment over CHADS₂ and CHA₂DS₂-VASc were assessed with the c-statistic, net reclassification improvement, and integrated discrimination improvement. We focused on the 1-year outcomes in our analyses. RESULTS Of 8,962 eligible individuals, 5,912 (66%) had nonvalvular AF and available eGFR data. Renal impairment by both creatinine and eGFR definitions was associated with higher rates of IS/TE at 1 year, compared with normal renal function. After adjustment for CHADS₂ risk factors, renal impairment did not significantly increase the risk of IS/TE at 1 year (hazard ratio: 1.06; 95% confidence interval [CI]: 0.75 to 1.49 for renal impairment; and hazard ratio: 1.09; 95% CI: 0.84 to 1.41 for eGFR). When renal impairment was added to existing risk scoring systems for stroke/TE (CHADS₂ and CHA₂DS₂-VASc), it did not independently add to the predictive value of the scores, whether defined by serum creatinine level or eGFR. This was evident even when the analysis was confined to only those patients with at least 1 year of follow-up. CONCLUSIONS Renal impairment was not an independent predictor of IS/TE in patients with AF and did not significantly improve the predictive ability of the CHADS₂ or CHA₂DS₂-VASc scores.

Risk Factors for Stroke and Thromboembolism in Relation to Age Among Patients With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BACKGROUND According to the latest European guidelines on the management of nonvalvular atrial fibrillation (NVAF), all patients aged ≥ 65 years should be treated with oral anticoagulation (if not contraindicated). Therefore, stroke risk factors should be investigated exclusively in patients with NVAF aged < 65 years. METHODS Patients diagnosed with NVAF in a four-hospital institution between 2000 and 2010 were identified. Event rates of stroke/thromboembolism were calculated according to age category (ie, age < 65, 65-74, and ≥ 75 years). Independent risk factors of stroke and thromboembolism were investigated in univariate and multivariate Cox regression models including patients with NVAF aged < 65 years only. The effect of adding vascular disease to the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke) score was examined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models. RESULTS Among 6,438 patients with NVAF, 2,002 (31.1%) were aged < 65 years. In patients with no CHADS(2) risk factors who were not treated with anticoagulation (n = 1,035), the stroke/thromboembolic event rate per 100 person-years was 0.23 (95% CI, 0.08-0.72), 2.05 (95% CI, 1.07-3.93), and 3.99 (95% CI, 2.63-6.06) in those aged < 65, 65-74, and ≥ 75 years, respectively. Heart failure, previous stroke, and vascular disease were significantly associated with increased risk of stroke/thromboembolism in both univariate and multivariate analyses, and vascular disease significantly improved the predictive ability of the CHADS(2) score (NRI, 0.40; IDI, 0.031). CONCLUSIONS Patients with NVAF aged ≥ 65 years have event rates that merit oral anticoagulation. In patients with NVAF aged < 65 years, the risk of stroke/thromboembolism is independently increased by the presence of heart failure, previous stroke, or vascular disease. As proposed in the new CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke, vascular disease, age 65-74 years, sex category [female]) score, stroke risk stratification by the CHADS(2) score can be improved by the addition of age 65 to 74 years and vascular disease.

Original ResearchCardiovascular DiseaseRisk Factors for Stroke and Thromboembolism in Relation to Age Among Patients With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BACKGROUND According to the latest European guidelines on the management of nonvalvular atrial fibrillation (NVAF), all patients aged ≥ 65 years should be treated with oral anticoagulation (if not contraindicated). Therefore, stroke risk factors should be investigated exclusively in patients with NVAF aged < 65 years. METHODS Patients diagnosed with NVAF in a four-hospital institution between 2000 and 2010 were identified. Event rates of stroke/thromboembolism were calculated according to age category (ie, age < 65, 65-74, and ≥ 75 years). Independent risk factors of stroke and thromboembolism were investigated in univariate and multivariate Cox regression models including patients with NVAF aged < 65 years only. The effect of adding vascular disease to the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke) score was examined by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models. RESULTS Among 6,438 patients with NVAF, 2,002 (31.1%) were aged < 65 years. In patients with no CHADS(2) risk factors who were not treated with anticoagulation (n = 1,035), the stroke/thromboembolic event rate per 100 person-years was 0.23 (95% CI, 0.08-0.72), 2.05 (95% CI, 1.07-3.93), and 3.99 (95% CI, 2.63-6.06) in those aged < 65, 65-74, and ≥ 75 years, respectively. Heart failure, previous stroke, and vascular disease were significantly associated with increased risk of stroke/thromboembolism in both univariate and multivariate analyses, and vascular disease significantly improved the predictive ability of the CHADS(2) score (NRI, 0.40; IDI, 0.031). CONCLUSIONS Patients with NVAF aged ≥ 65 years have event rates that merit oral anticoagulation. In patients with NVAF aged < 65 years, the risk of stroke/thromboembolism is independently increased by the presence of heart failure, previous stroke, or vascular disease. As proposed in the new CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke, vascular disease, age 65-74 years, sex category [female]) score, stroke risk stratification by the CHADS(2) score can be improved by the addition of age 65 to 74 years and vascular disease.

Assessing the Risk of Bleeding in Patients with Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

Background—Management decisions for thromboprophylaxis in atrial fibrillation need to balance the risk of stroke against serious hemorrhage. The objective of the present analysis is to compare the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly (HAS-BLED) score against other older bleeding risk scores and the new Anticoagulation and Risk Factors in Atrial Fibrillation score in an atrial fibrillation cohort. Methods and Results—Patients diagnosed with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were identified. Independent risk factors of bleeding were investigated using Cox regression. The predictive value of several bleeding risk schema was assessed using the c-statistic and net reclassification improvement. Oral anticoagulation use was highest in moderate-risk patients (59.8%) but only slightly more than high-risk (50.1%) and low-risk (46.4%) patients. Those at higher bleeding risk (HAS-BLED ≥3) were also at highest risk of stroke/thromboembolism or stroke/thromboembolism/death, as well as bleeding and all-cause mortality. On multivariable analysis, independent predictors of bleeding were age ≥75 years and age ≥65 years, alcohol excess, anemia, and heart failure. All risk scores had only modest predictive ability for bleeding, whether on vitamin K antagonist or not (c-statistic ≈0.6). When the HAS-BLED score was compared with other bleeding risk scores, the net reclassification improvement was significantly improved against all other scores tested. Conclusions—Current oral anticoagulation prescribing patterns would suggest that bleeding risk estimation by clinicians is poor and that oral anticoagulation prescribing does not reflect bleeding risk per se. The HAS-BLED score performs well in relation to predicting bleeding events compared with older bleeding scores and the Anticoagulation and Risk Factors in Atrial Fibrillation score, with significantly improved reclassification using HAS-BLED compared with all other bleeding risk scores tested.Background— Management decisions for thromboprophylaxis in atrial fibrillation need to balance the risk of stroke against serious hemorrhage. The objective of the present analysis is to compare the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly (HAS-BLED) score against other older bleeding risk scores and the new Anticoagulation and Risk Factors in Atrial Fibrillation score in an atrial fibrillation cohort. Methods and Results— Patients diagnosed with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were identified. Independent risk factors of bleeding were investigated using Cox regression. The predictive value of several bleeding risk schema was assessed using the c-statistic and net reclassification improvement. Oral anticoagulation use was highest in moderate-risk patients (59.8%) but only slightly more than high-risk (50.1%) and low-risk (46.4%) patients. Those at higher bleeding risk (HAS-BLED ≥3) were also at highest risk of stroke/thromboembolism or stroke/thromboembolism/death, as well as bleeding and all-cause mortality. On multivariable analysis, independent predictors of bleeding were age ≥75 years and age ≥65 years, alcohol excess, anemia, and heart failure. All risk scores had only modest predictive ability for bleeding, whether on vitamin K antagonist or not (c-statistic ≈0.6). When the HAS-BLED score was compared with other bleeding risk scores, the net reclassification improvement was significantly improved against all other scores tested. Conclusions— Current oral anticoagulation prescribing patterns would suggest that bleeding risk estimation by clinicians is poor and that oral anticoagulation prescribing does not reflect bleeding risk per se. The HAS-BLED score performs well in relation to predicting bleeding events compared with older bleeding scores and the Anticoagulation and Risk Factors in Atrial Fibrillation score, with significantly improved reclassification using HAS-BLED compared with all other bleeding risk scores tested.

A Prospective Study of Estimated Glomerular Filtration Rate and Outcomes in Patients With Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BACKGROUND Atrial fibrillation (AF) is more likely to develop in patients with chronic kidney disease (CKD) than in individuals with normal renal function, and patients with CKD are more likely to suffer ischemic stroke (IS)/thromboembolism (TE). To our knowledge, no prior study has considered the impact of estimated glomerular filtration rate (eGFR) on bleeding. We investigated the relationship of eGFR to IS/TE, mortality, and bleeding in an AF population unrestricted by age or comorbidity. METHODS Patients with nonvalvular AF (NVAF) were stratified into five categories according to eGFR (≥ 90, 60-89, 30-59, 15-29, and < 15 mL/min/1.73 m2), analyzing risk factors, all-cause mortality, bleeding, and IS/TE. Of 8,962 eligible individuals, 5,912 had NVAF and available serum creatinine data, with 14,499 patient-years of follow-up. RESULTS The incidence rates of IS/TE were 7.4 and 7.2 per 1,000 person-years in individuals not receiving and receiving anticoagulation therapy, respectively. Rates of all-cause mortality were 13.4 and 9.4 per 1,000 person-years, respectively, and of major bleeding, 6.2 and 9.0 per 1,000 person-years, respectively. Rates increased with decreasing eGFR, with IS/TE rates being lower in individuals receiving oral anticoagulation (OAC) therapy. eGFR was not an independent predictor of IS/TE on multivariate analyses. When the benefit of IS reduction is balanced against the increased risk of hemorrhagic stroke, the net clinical benefit (NCB) was clearly positive in favor of OAC use. CONCLUSIONS Incidence rates of IS/TE, mortality, and bleeding increased with reducing eGFR across the whole range of renal function. OAC use was associated with a lower incidence of IS/TE and mortality at 1 year compared with individuals not receiving anticoagulants in all categories of renal function as measured by eGFR. The NCB balancing IS against serious bleeding was positive in favor of OAC use among patients with renal impairment.

Prognosis in Patients Hospitalized With Permanent and Nonpermanent Atrial Fibrillation in Heart Failure

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with an increased mortality. This study evaluated the prognosis of permanent and nonpermanent AF in patients with both AF and HF. All AF patients seen in our institution were identified and followed up. We included 1,906 patients suffering from AF and HF: 839 patients (44%) had preserved left ventricular ejection fraction (LVEF) and 1,067 patients (56%) had decreased LVEF; 1,056 patients (55%) had nonpermanent AF and 850 patients (45%) had permanent AF. During a median follow-up of 1.9 years (interquartile range 0.3 to 5.0), 377 patients died, 462 were readmitted for HF, and 200 had stroke or thromboembolic events. In patients with decreased LVEF, the rate of death was similar in patients with permanent or nonpermanent AF. In patients with preserved LVEF, permanent AF was associated with a higher risk of death and a higher risk of HF hospitalization. Stroke risk did not differ with permanent AF whatever the LVEF. NYHA functional class was an independent predictor of death (risk ratio [RR]=1.33, 95% confidence interval [CI] 1.12 to 1.59, p=0.001), as was permanent AF (RR=1.79, 95%CI 1.32 to 2.42, p=0.0002). Permanent AF (RR=1.52, 95% CI 1.20 to 1.93, p=0.0006) was also an independent predictor of readmission for HF. In conclusion, in patients with AF and HF, the risk of admission for HF and risk of death were higher when AF was permanent, particularly in patients with preserved LVEF. Stroke risk did not differ according to the pattern of AF, whatever the LVEF.

Geographic Variations in the Quality of Oral Anticoagulation With Vitamin K Antagonists in the Era of New Anticoagulants

A number of new drugs that do not exhibit the limitations of vitamin K antagonists (VKA) have now been evaluated for oral anticoagulation (OAC). These include direct thrombin inhibitors (dabigatran) and direct factor Xa inhibitors (eg, rivaroxaban, apixaban). Recent studies in patients with atrial

A 10-year prospective study of estimated glomerular filtration rate and outcomes with oral anticoagulation in patients with atrial fibrillation

Individuals with chronic kidney disease (CKD) are more likely to develop atrial fibrillation (AF) than individuals with normal renal function, and are more likely to suffer stroke/ thromboembolism (TE). Only one study has considered the association between estimated glomerular filtration rate (eGFR) and stroke/TE, and none have considered impact of eGFR on bleeding. We therefore conducted the first long-term prospective study of eGFR and stroke/TE, mortality and bleeding in an AF population, unrestricted by age or comorbidity. Methods: Patients diagnosed with non-valvular AF (NVAF) and available eGFR data in a four-hospital institution between 2000 and 2010 were identified. The study population was stratified into five categories according to eGFR (in ml/min/1.73 m2): ≥90, 60-89, 30-59, 15-29, and <15, analysing risk factors, as well as incidence and survival for all-cause mortality, bleeding and stroke/TE. Results: Of 8962 eligible individuals, 5912 (66.0%) had NVAF and available eGFR data. In non-anticoagulated and anticoagulated individuals, rates of stroke/TE were 7.4 (95% CI 6.3-8.6) and 7.2 (6.3-8.2) per 1000 person years, respectively. Incidence rates of all-cause mortality were 13.4 (12.0-15.0) and 9.4 (8.3-10.5), respectively, and of major bleeding were 6.2 (5.2-7.3) and 9.0 (8.0-10.1) per 1000 person years, respectively. Rates of all events increased with decreasing eGFR, regardless of OAC, and rates of stroke/TE were lower in individuals receiving OAC. When the benefit of ischaemic stroke reduction is balanced against the increased risk of haemorrhagic stroke amongst patients with renal impairment, the net clinical benefit (NCB) was clearly positive in favour of OAC use: for individuals with a eGFR=30-59, NCB=2.06 (95% CI 1.40-2.88), whilst for eGFR <30, NCB=6.69 (3.27-12.78). At 10 years, in individuals with eGFR >60 mL/min/1.73m2and with eGFR <30 mL/min/1.73m2, overall rates of stroke/TE were 17.7% and 30.7%, respectively. Overall rates of all-cause mortality were 21.7% and 66.8%, and of bleeding were 21.9% and 47.1%, respectively. Conclusion: Renal impairment is a poor prognostic indicator of stroke/TE, bleeding and mortality in the short-term and the long-term in individuals with NVAF across the whole range of renal function. OAC use was associated with a lower incidence of stroke/TE and mortality over 10 years, compared with non-anticoagulated individuals in all categories of renal function as measured by eGFR. The NCB balancing ischaemic stroke against serious bleeding was positive, in favour of OAC use amongst patients with renal impairment.

Assessing the Risk of Bleeding in Patients With Atrial FibrillationClinical Perspective

Background—Management decisions for thromboprophylaxis in atrial fibrillation need to balance the risk of stroke against serious hemorrhage. The objective of the present analysis is to compare the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly (HAS-BLED) score against other older bleeding risk scores and the new Anticoagulation and Risk Factors in Atrial Fibrillation score in an atrial fibrillation cohort. Methods and Results—Patients diagnosed with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were identified. Independent risk factors of bleeding were investigated using Cox regression. The predictive value of several bleeding risk schema was assessed using the c-statistic and net reclassification improvement. Oral anticoagulation use was highest in moderate-risk patients (59.8%) but only slightly more than high-risk (50.1%) and low-risk (46.4%) patients. Those at higher bleeding risk (HAS-BLED ≥3) were also at highest risk of stroke/thromboembolism or stroke/thromboembolism/death, as well as bleeding and all-cause mortality. On multivariable analysis, independent predictors of bleeding were age ≥75 years and age ≥65 years, alcohol excess, anemia, and heart failure. All risk scores had only modest predictive ability for bleeding, whether on vitamin K antagonist or not (c-statistic ≈0.6). When the HAS-BLED score was compared with other bleeding risk scores, the net reclassification improvement was significantly improved against all other scores tested. Conclusions—Current oral anticoagulation prescribing patterns would suggest that bleeding risk estimation by clinicians is poor and that oral anticoagulation prescribing does not reflect bleeding risk per se. The HAS-BLED score performs well in relation to predicting bleeding events compared with older bleeding scores and the Anticoagulation and Risk Factors in Atrial Fibrillation score, with significantly improved reclassification using HAS-BLED compared with all other bleeding risk scores tested.Background— Management decisions for thromboprophylaxis in atrial fibrillation need to balance the risk of stroke against serious hemorrhage. The objective of the present analysis is to compare the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly (HAS-BLED) score against other older bleeding risk scores and the new Anticoagulation and Risk Factors in Atrial Fibrillation score in an atrial fibrillation cohort. Methods and Results— Patients diagnosed with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were identified. Independent risk factors of bleeding were investigated using Cox regression. The predictive value of several bleeding risk schema was assessed using the c-statistic and net reclassification improvement. Oral anticoagulation use was highest in moderate-risk patients (59.8%) but only slightly more than high-risk (50.1%) and low-risk (46.4%) patients. Those at higher bleeding risk (HAS-BLED ≥3) were also at highest risk of stroke/thromboembolism or stroke/thromboembolism/death, as well as bleeding and all-cause mortality. On multivariable analysis, independent predictors of bleeding were age ≥75 years and age ≥65 years, alcohol excess, anemia, and heart failure. All risk scores had only modest predictive ability for bleeding, whether on vitamin K antagonist or not (c-statistic ≈0.6). When the HAS-BLED score was compared with other bleeding risk scores, the net reclassification improvement was significantly improved against all other scores tested. Conclusions— Current oral anticoagulation prescribing patterns would suggest that bleeding risk estimation by clinicians is poor and that oral anticoagulation prescribing does not reflect bleeding risk per se. The HAS-BLED score performs well in relation to predicting bleeding events compared with older bleeding scores and the Anticoagulation and Risk Factors in Atrial Fibrillation score, with significantly improved reclassification using HAS-BLED compared with all other bleeding risk scores tested.