Hypertension, Abnormal Renal/liver Function, Stroke, Bleeding History Or Predisposition Score Research Articles

Available Bleeding Scoring Systems Poorly Predict Major Bleeding in the Acute Phase of Pulmonary Embolism.

We aimed to compare six available bleeding scores, in a real-life cohort, for prediction of major bleeding in the early phase of pulmonary embolism (PE). We recorded in-hospital characteristics of 2754 PE patients in a prospective observational multicenter cohort contributing 18,028 person-days follow-up. The VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), ORBIT (Outcomes Registry for Better Informed Treatment), HEMORR2HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol) scores were assessed at baseline. International Society on Thrombosis and Haemostasis (ISTH)-defined bleeding events were independently adjudicated. Accuracy of the overall original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared. We observed 82 first early major bleedings (3.0% (95% CI, 2.4–3.7)). The predictive power of bleeding scores was poor (Harrel’s C-index from 0.57 to 0.69). The RIETE score had numerically higher model fit and discrimination capacity but without reaching statistical significance versus the ORBIT, HEMORR2HAGES, and ATRIA scores. The VTE-BLEED and HAS-BLED scores had significantly lower C-index, integrated discrimination improvement, and net reclassification improvement compared to the others. The rate of observed early major bleeding in score-defined low-risk patients was high, between 15% and 34%. Current available scoring systems have insufficient accuracy to predict early major bleeding in patients with acute PE. The development of acute-PE-specific risk scores is needed to optimally target bleeding prevention strategies.

Thromboembolism, mortality, and bleeding in 2,435,541 atrial fibrillation patients with and without cancer: A nationwide cohort study.

The number of patients with atrial fibrillation (AF) and cancer is rapidly increasing in clinical practice. The impact of cancer on clinical outcomes in this patient population is unclear, as is the performance of the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) and CHA2 DS2 -VASc (Congestive Heart Failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Stroke or Transient Ischemic Attack, Vascular Disease, Age 65 to 74 Years, Sex Category) scores. This was an observational, retrospective cohort study including 2,435,541 adults hospitalized with AF. The authors investigated the incidence rates (IRs) of all-cause and cardiovascular mortality, ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) according to the presence of cancer and cancer types. Overall, 399,344 (16.4%) had cancer, with the most common cancers being metastatic, prostatic, colorectal, lung, breast, and bladder. During a mean follow-up of 2.0 years, cancer increased all-cause mortality (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.99-2.01). The IR of ischemic stroke was higher with pancreatic cancer (2.8%/y), uterine cancer (2.6%/y), and breast cancer (2.6%/y), whereas it was lower with liver/lung cancer (1.9%/y) and leukemia/myeloma (2.0%/y), in comparison with noncancer patients (2.4%/y). Cancer increased the risk of major bleeding (HR, 1.27; 95% CI, 1.26-1.28) and ICH (HR, 1.07; 95% CI, 1.05-1.10). Leukemia, liver cancer, myeloma, and metastatic cancers showed the highest IRs for major bleeding/ICH. Major bleeding and ICH rates progressively increased with the HAS-BLED score, which showed generally good predictivity with C indexes > 0.70 for all cancer types. The CHA2 DS2 -VASc score's predictivity was slightly lower in AF patients with cancer. Cancer increased all-cause mortality, major bleeding, and ICH risk in AF patients. The association between cancer and ischemic stroke differed among cancer types, and in some types, the risk of bleeding seemed to exceed the thromboembolic risk.

The Extended Utility of CHA2DS2VASc and HAS-BLED Scores in the Selection for Transcutaneous Left Atrial Appendage Closure.

Background and purpose: Left atrial appendage closure (LAAC) is an option for stroke prevention in atrial fibrillation patients. Randomized studies have demonstrated the effectiveness and safety of LAAC but included patients with an average risk of stroke and bleeding complications. The current study aimed to assess the extended utility of CHA2DS2VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke, transient ischemic attack, or thromboembolism [doubled]; vascular disease; age 65 to 75 years; and sex category) and HAS-BLED (hypertension; abnormal renal/liver function; stroke; bleeding history or predisposition; labile INR, elderly, drugs/alcohol concomitantly) scores for qualification and prognosis after LAAC. Methods: The study population comprised 270 patients aged 72.8 ± 8.78 years. The occluders used were the Amplatzer Amulet (N = 205), Amplatzer Cardiac Plug (N = 53), and Watchman device (N = 12). The prognosis after LAAC was analyzed for different cohorts of patients distinguished based on different CHA2DS2VASc and HAS-BLED scores. The mean duration of follow-up was 21.6 ± 10.3 months. Results: The observed rates of ischemic stroke and bleeding were much lower than that expected (2.2% vs. 5.6%, and 0.76% vs. 6.05%, respectively). The mortality rate did not differ concerning the CHA2DS2CVASc score. It was significantly lower (8.3%) for HAS-BLED < 3, and it raised to 17.9% for HAS-BLED = 3 and to 25.9% for HAS-BLED > 3. Significant differences (p = 0.003) occurred for Kaplan–Meier curves for extreme HAS-BLED subgroups. A composite endpoint was most often found in high/very high risk of bleeding patients. Conclusions: HAS-BLED, but not CHA2DS2CVASc score, may be a useful tool to predict the prognosis of patients after LAAC. Qualification for LAAC based on the risk of stroke should not differ from qualification for anticoagulation. Despite the worse prognosis of patients with the highest bleeding risk, this group is likely to experience the greatest benefit from reducing the bleeding risk from LAAC.

Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding.

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67–77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17–63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p < 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65–2.79, p < 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03–1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15–2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58–0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR2HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance.

Comparison of HAS-BLED and HAS-BED Versus CHADS2 and CHA2DS2VASC Stroke and Bleeding Scores in Patients With Atrial Fibrillation

Anticoagulation is recommended in patients with atrial fibrillation (AF) for stroke prevention, and the bleeding risk associated suggests the need for a bleeding risk stratification. HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio (INR), elderly >65years, drugs/alcohol concomitantly) score includes "labile INR" referred to quality of anticoagulation. However, in naïve patients, this item is not available. In addition, stroke and bleeding risk prediction scores shared several risk factors. The aims of our study were as follows: (1) to evaluate if the HAS-BLED score in its refined form excluding "labile INR" (HAS-BED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, elderly, drugs/alcohol]) is still associated with bleeding risk and (2) to evaluate the predictive ability for bleeding of both stroke and bleeding prediction models. We followed an inception cohort of 4,579 patients with AF enrolled in the Survey on anticoagulaTed pAtients RegisTer (NCT02219984). Major bleeds were recorded. During follow-up (7,014 patient-years), 115 patients experienced a major bleeding (MB; rate 1.6× 100 patient-years). Patients at high risk were better identified by HAS-BLED and HAS-BED scores with respect to CHADS2 (congestive heart failure, hypertension, age >75years, diabetes, previous stroke or transient ischemic attack) and CHA2DS2VASc (congestive heart, failure, hypertension, age [>75years], diabetes, stroke/transient ischemic attack, vascular disease, age [65 to 74years], female gender). HAS-BLED has a slightly higher c value in comparison to CHADS2 and CHA2DS2VASc. However, among naïve patients, the predictive ability for hemorrhage of HAS-BED score is overlapping with CHADS2 and CHA2DS2VASc. In low stroke risk patients (CHA2DS2VASc= 0 to 1), only 6 patients are at high bleeding risk, and none of them experienced MB. In conclusion, in our prospective cohort of patients with AF, we found that HAS-BLED and HAS-BED scores identify patients at high bleeding risk. However, the predictive value for MB of HAS-BED used in naïve patients is similar to CHADS2 or CHA2DS2VASc, suggesting that stroke stratification scores could be sufficient for tailoring treatment.

Effects of Oral Anticoagulant Therapy in Medical Inpatients ≥65 Years With Atrial Fibrillation

In this retrospective cohort observational study, we investigated mortality, ischemic, and hemorrhagic events in patients ≥65 years with atrial fibrillation consecutively discharged from an Acute Geriatric Ward in the period 2010 to 2013. Stroke and bleeding risk were evaluated using CHA2DS2-VASC (congestive heart failure/left ventricular dysfunction, hypertension, aged ≥75 years, diabetes mellitus, stroke/transient ischemic attack/systemic embolism, vascular disease, aged 65 to 74 years, gender category) and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) scores. Co-morbidity, cognitive status, and functional autonomy were evaluated using standardized scales. Independent associations among clinical variables, including use of vitamin K antagonist-based oral anticoagulant therapy (OAT), all-cause mortality, and fatal and nonfatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 980 patients discharged (mean age 83 years, 60% women, roughly 30% cognitively impaired or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.8 and 2.1, respectively), 505 (51.5%) died during a mean follow-up period of 571 days; ischemic and hemorrhagic stroke occurred in 82 (12.3%) and 13 patients (1.3%), respectively, and major bleedings in 43 patients (4.4%). Vitamin K antagonists' use was independently associated with reduced mortality (odds ratio 0.524) and with a nonsignificant reduction in incidence of ischemic stroke, without excess in bleeding risk. Similar findings were observed in the 2 propensity score-matched cohorts of patients. In conclusion, among vulnerable patients with atrial fibrillation ≥65 years with high post-discharge death rate, OAT was associated, among other multiple factors, with reduced mortality.

The HAS-BLED Score Has Better Prediction Accuracy for Major Bleeding Than CHADS2 or CHA2DS2-VASc Scores in Anticoagulated Patients With Atrial Fibrillation

The aim of this study was to test the hypothesis that a specific bleeding risk score, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), was better at predicting major bleeding compared with CHADS2 (congestive heart failure, hypertension, 75 years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) in anticoagulated atrial fibrillation (AF) patients. The CHADS2 and CHA2DS2-VASc scores are well-validated stroke risk prediction scores for AF, but are also associated with increased bleeding and mortality. We recruited 1,370 consecutive AF patients (49% male; median age, 76 years) receiving oral anticoagulation therapy from our outpatient anticoagulation clinic, all of whom were receiving acenocoumarol and had an international normalized ratio between 2.0 and 3.0 during the preceding 6 months. During follow-up, major bleeding events were identified by the 2005 International Society on Thrombosis and Haemostasis criteria. Model performance was evaluated by calculating the C-statistic, and the improvement in predictive accuracy was evaluated by calculating the net reclassification improvement and integrated discrimination improvement. After a median follow-up of 996 (range, 802 to 1,254) days, 114 patients (3.0%/year) presented with a major bleeding event; 31 of these events were intracranial hemorrhages (0.8%/year). Based on the C-statistic, HAS-BLED had a model performance superior to that of both CHADS2 and CHA2DS2-VASc (both p < 0.001). Both net reclassification improvement and integrated discrimination improvement analyses also show that HAS-BLED was more accurately associated with major bleeding compared with CHADS2 and CHA2DS2-VASc scores. In anticoagulated AF patients, a validated specific bleeding risk score, HAS-BLED, should be used for assessing major bleeding. The practice of using CHADS2 and CHA2DS2-VASc as a measure of high bleeding risk should be discouraged, given its inferior predictive performance compared with the HAS-BLED score.

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Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation

Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF. We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0-3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0-6; 29% with a score ≥3 [ie, high risk]). Median follow-up was 861 days (range, 718-1016 days). Independent predictors for major bleeding were age ≥75 years (hazard ratio [HR], 1.74; 95% CI, 1.05-2.87; P=0.030), male sex (HR, 1.70; 95% CI, 1.03-2.80; P=0.036), renal impairment (HR, 2.12; 95% CI, 1.20-3.73; P=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73-9.67; P<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03-5.06; P=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13-4.18; P=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40-3.46; P=0.001), heart failure (HR, 1.78; 95% CI, 1.20-2.86; P=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20-2.86; P<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68-2.49; P<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27-1.81; P<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all-cause mortality (HR, 1.68; 95% CI, 1.40-2.01; P<0.001). The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events.