The high-risk bleeding category of different scores in patients with venous thromboembolism: Systematic review and meta-analysis

BackgroundIn patients with venous thromboembolism (VTE), bleeding risk should be carefully assessed but none of the available risk scores is currently recommended. The aim of this study was to systematically evaluate the performance of bleeding scores in patients with VTE focusing on high-risk patients.MethodsLongitudinal studies were searched in Medline and Cochrane Library, as well as reviews and references of retrieved articles. Studies were identified, data were extracted, and reporting quality was evaluated. We determined the sensitivity, specificity, positive likelihood ratio (LR+), and diagnostic odds ratio (DOR) of the ‘high risk’ category of each bleeding score. Random effects meta-analysis was performed in order to derive the central estimates and 95% confidence intervals (95% CI).ResultsTwenty-one studies and ten bleeding scores fulfilled the inclusion criteria. VTE-BLEED showed the highest sensitivity but the second-lowest specificity (Se 76%; Sp 61%), followed by ACCP (Se 59%; Sp 57%). The remaining scores had high specificity (> 80%) but a low sensitivity (< 20%). HEMORR₂HAGES and Niewenhuis score showed the best performance regarding LR+ that was 2.67 and 5.91, respectively. Regarding DOR, the Niewenhuis score and VTE-BLEED were the best performers with 9.04; 95% CI 3.87–21.09 and 4.94 95% CI 2.66–9.09, respectively. In a cohort with patients predominantly treated with direct oral anticoagulants (DOACs), VTE-BLEED had the highest sensitivity (Se 77%; Sp 60%).ConclusionsOverall, the majority of the risk scores showed a moderate ability to forecast major bleeding events, with the VTE-BLEED as the most sensitive in patients treated with DOACs.     

Comparing Bleeding Risk Assessment Focused on Modifiable Risk Factors Only Versus Validated Bleeding Risk Scores in Atrial Fibrillation

Background

There is uncertainty whether a focus on modifiable bleeding risk factors offers better prediction of major bleeding than other existing bleeding risk scores.

Performance of the HAS-BLED high bleeding-risk category,compared to ATRIA and HEMORR2HAGES in patients with atrial fibrillation: a systematic review and meta-analysis

Introduction

Atrial fibrillation (AF) patients’ major bleeding risk should be evaluated through risk scores such as HAS-BLED, HEMORR2HAGES or ATRIA. These scores were validated in independent studies with different methods. Therefore, we aimed to review and estimate the value added by ATRIA and HEMORR2HAGES compared to HAS-BLED.

Methods

Medline and Cochrane Library (July 2013) were searched, as well as reviews and references of obtained articles. We looked for studies reporting data for diagnostic accuracy of HAS-BLED with any of HEMORR2HAGES or ATRIA scores, concerning Major Bleeding events. We determined the sensitivity, specificity, and diagnostic odds ratio (DOR) of ATRIA and HEMORR2HAGES compared to HAS-BLED within the same studies. Random effects meta-analysis was performed in order to derive diagnostic accuracy estimates. Heterogeneity was assessed through I ² test.

Results

Six studies fulfilled inclusion criteria. Five studies evaluated simultaneously HAS-BLED and HEMORR2HAGES. Sensitivity, specificity, and DOR were respectively 0.53 (0.52–0.54), 0.65 (0.65–0.65) and 2.11 (1.91–2.35) for HAS-BLED, and 0.27 (0.26–0.27), 0.89 (0.89–0.89) and 2.90 (2.77–3.04) for HEMORR2HAGES. Four studies compared HAS-BLED with ATRIA. Sensitivity, specificity, and DOR were respectively 0.41 (0.35–0.48), 0.78 (0.76–0.79) and 2.22 (1.08–4.55) for HAS-BLED, and 0.23 (0.17–0.29), 0.91 (0.90–0.91) and 1.98 (1.29–3.03) for ATRIA.

Conclusions

The ‘high-risk’ categories of the evaluated major bleeding-risk scores are not sensitive. HAS-BLED, due to its sensitivity (compared to other scores) and ease to apply, is recommended for the assessment of AF patients’ major bleeding risk.     

Erratum to: Dual antiplatelet therapy with or without oral anticoagulation in the postdischarge management of acute coronary syndrome patients with an indication for long term anticoagulation: a systematic review

Bleeding-prediction scores may help guiding management of patients with pulmonary embolism (PE), although no such score has been validated. We aimed to externally validate and compare two bleeding-prediction scores for venous thromboembolism to three scores developed for patients with atrial fibrillation in a real-world cohort of PE patients. We performed a prospective observational cohort study in 448 consecutive PE patients who were treated with heparins followed by vitamin-K-antagonists. The Kuijer, RIETE, HEMORR₂HAGES, HAS-BLED and ATRIA scores were assessed at baseline. All patients were followed for the occurrence of major bleeding over a 30-day period. The accuracies of both the overall, original 3-level and newly defined optimal 2-level outcome of the scores were evaluated and compared, both for the 30-day period as well as for bleeding occurring in versus after the first week of treatment. 20 of 448 patients suffered major bleeding resulting in a cumulative incidence of 4.5 % (95 % CI 2.5–6.5). The predictive power of all five scores for bleeding was poor (c-statistics 0.57–0.64), both for the 3-level and 2-level score outcomes. No individual score was found to be superior. The HAS-BLED score had a good c-statistic for bleedings occurring after the first week of treatment (0.75, 95 % CI 0.47–1.0). Current available scoring systems have insufficient accuracy to predict overall anticoagulation-associated bleeding in patients treated for acute PE. To optimally target bleeding-prevention strategies, the development of a high quality PE-specific risk score is urgently needed.     

Machine learning to predict major bleeding during anticoagulation for venous thromboembolism: possibilities and limitations

Predictive tools for major bleeding (MB) using machine learning (ML) might be advantageous over traditional methods. We used data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) to develop ML algorithms to identify patients with venous thromboembolism (VTE) at increased risk of MB during the first 3 months of anticoagulation. A total of 55 baseline variables were used as predictors. New data prospectively collected from the RIETE were used for further validation. The RIETE and VTE-BLEED scores were used for comparisons. External validation was performed with the COMMAND-VTE database. Learning was carried out with data from 49 587 patients, of whom 873 (1.8%) had MB. The best performing ML method was XGBoost. In the prospective validation cohort the sensitivity, specificity, positive predictive value and F1 score were: 33.2%, 93%, 10%, and 15.4% respectively. F1 value for the RIETE and VTE-BLEED scores were 8.6% and 6.4% respectively. In the external validation cohort the metrics were 10.3%, 87.6%, 3.5% and 5.2% respectively. In that cohort, the F1 value for the RIETE score was 17.3% and for the VTE-BLEED score 9.75%. The performance of the XGBoost algorithm was better than that from the RIETE and VTE-BLEED scores only in the prospective validation cohort, but not in the external validation cohort.     

The HAS‐BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta‐analysis

Our objective was to compare the diagnostic accuracy between the HAS‐BLED score and any of HEMORR₂HAGES, ATRIA, CHADS₂, or CHA₂DS₂‐VASc scores in anticoagulated patients with atrial fibrillation. We systematically searched the Cochrane Library, MEDLINE, PubMed, and Embase databases for relevant studies. Data were extracted and analyzed according to predefined clinical endpoints. Eleven studies were identified. Discrimination analysis demonstrates that HAS‐BLED has no significant C‐statistic differences for bleeding risk prediction compared with ATRIA or HEMORR₂HAGES, but it has significant differences compared with CHADS₂ or CHA₂DS₂‐VASc. The significant positive net reclassification improvement and integrated discrimination improvement values also show that HAS‐BLED is superior to that of any of HEMORR₂HAGES, ATRIA, CHADS₂, or CHA₂DS₂‐VASc scores. According to calibration analysis of HAS‐BLED, it overpredicts the risk of bleeding in the low (risk ratio [RR]: 1.16, 95% confidence interval [CI]: 0.63‐2.13, P = 0.64) risk stratification but underpredicts that in the moderate (RR: 0.66, 95% CI: 0.51‐0.86, P = 0.002) and high (RR: 0.88, 95% CI: 0.70‐1.10, P = 0.27) risk stratifications. The HAS‐BLED score not only performs better than the HEMORR₂HAGES and ATRIA bleeding scores, but it also is superior to the CHADS₂ and CHA₂DS₂‐VASc stroke scores for bleeding prediction. The HAS‐BLED score should be the optimal choice to assess major bleeding risk in clinical practice.     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

HAS-BLED and CHA2DS2-VASc Scores as Predictors of Bleeding and Thrombotic Risk After Continuous-Flow Ventricular Assist Device Implantation

BackgroundHAS-BLED and CHA₂DS₂-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation.Methods and ResultsBaseline HAS-BLED and CHA₂DS₂-VASc scores were retrospectively determined for 173 consecutive patients who underwent HeartMate II CF-VAD implantation at a single center from 2005 to 2011. Forty-three patients had bleeding (24.9%) and 22 had TE (12.7%) events over a 290 patient-year follow-up period. The mean ± SD HAS-BLED scores were 2.7 ± 1.0 and 1.9 ± 1.1 (P < .0001) in patients with and without bleeding, respectively. The CHA₂DS₂-VASc scores were 3.6 ± 1.4 and 2.9 ± 1.5 (P = .03) in patients with and without TE events, respectively. A HAS-BLED score of ≥3 was associated with a significantly higher risk of bleeding events compared with a score of <3 (42% vs 15%, respectively; hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.82–6.32; P < .001). A CHA₂DS₂-VASc score of ≥3 was associated with a higher risk of TE events compared with a score of <3 (18% vs 4%, respectively; HR 4.02, 95% CI 1.19–13.6; P = .025).ConclusionsBaseline HAS-BLED and CHA₂DS₂-VASc scores of ≥3 conferred significantly higher risks of bleeding and TE, respectively, following HeartMate II implantation.     

Relation of the HAS-BLED bleeding risk score to major bleeding,cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Background Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists (VKA) is closely related to bleeding risk.The HAS-BLED bleeding score has demonstrated its usefulness in assessing major bleeding risk in AF patients.However,risk factors for warfarin associated-bleeding also predict stroke risk in AF patients.We tested the usefulness of HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated AF patients.Methods and Results We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilised for at least 6 months on oral anticoagulation (OAC;INR 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 (718-1016) days.Independent predictors for major bleeding were age ≥75 [HR:1.74 (1.05-2.87);P=0.030],male sex [HR:1.70 (1.03-2.80);P=0.036],renal impairment [HR 2.12 (1.20-3.73);0.010],previous bleeding episode [HR 6.00 (3.73-9.67);P < 0.001],current alcoholic consumption [HR 2.28 (1.03-5.06);P=0.043] and the concomitant malignant disease [HR 2.17 (1.13-4.18);P=0.020].Independent predictors for adverse cardiovascular events were age > 75y [HR 2.20 (1.40-3.46);P=0.001],heart failure [HR 1.78 (1.20-2.86);P=0.001] and previous stroke [HR 1.85 (1.20-2.86);P < 0.001].The HAS-BLED score was highly predictive for major bleeding events [HR 2.04 (1.68-2.49);P < 0.001],and for adverse cardiovascular events [HR 1.51 (1.27-1.81);P < 0.001].The incidence of both bleeding and adverse cardiovascular events was higher as HASBLED 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 (1.40-2.01);P < 0.001].Conclusions The HAS-BLED score is not only useful in assessment of bleeding risk,but it showed some predictive value for cardiovascular events and mortality in anticoagulated AF patients,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.     

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes,for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

Background

The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication.

Methods

We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged > 35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database.

Results

Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3–7.6] and 1.9[1.1–3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67–0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p < 0.05, compared to other four scoring schemes).

Conclusion

The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.     

Predictors of increased risk of adverse cardiovascular outcomes among patients with myeloproliferative neoplasms and atrial fibrillation

BackgroundPatients with myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), have increased risk of cardiovascular (CV) disease. Atrial fibrillation (AF) is associated with adverse CV outcomes including arterial thrombosis, heart failure (HF), and CV death and coexists with MPN. Traditional risk scores (CHA2DS2-VASC and HAS-BLED) for estimating risks/benefits of anticoagulation to prevent thrombotic events in AF do not include MPN status. Therefore, we aimed to investigate CV outcomes in patients with MPN and AF and evaluate the predictive ability of traditional risk scores.MethodsWe conducted a single-center, retrospective cohort study of patients with MPN and AF. Primary outcome was composite of CV death and arterial thromboembolism; secondary outcomes were bleeding requiring emergency department visit or hospitalization, hospitalization for HF, and all-cause death. Multivariable competing-risk and Cox proportional hazards regression models were used to estimate risk of outcomes. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of composite outcome and bleeding, respectively.ResultsA total 142 patients was included (62 ET, 54 PV, 26 MF). Composite outcome, bleeding, HF hospitalization and all-cause death occurred in 39 %, 30 %, 34 %, and 48 %, of patients respectively. After multivariable modeling, MF was associated with increased risk of composite outcome (SHR 2.70, 95 % CI 1.38–5.27) and all-cause mortality (HR 9.77, 95 % CI 4.88–19.54) but not bleeding (SHR 1.19, 95 % CI 0.51–2.80) or HF admissions (SHR 0.57, 95 % CI 0.19–1.72). CHA2DS2-VASC and HAS-BLED were poor predictors of composite outcome (C-statistic 0.52, 95 % CI 0.43–0.62) and bleeding (C-statistic 0.49, 95 % CI 0.40–0.58), respectively.ConclusionIn patients with MPN and AF, MF is associated with increased risk of CV death and arterial thrombosis and traditional risk scores do not accurately predict outcomes in this patient population. Further investigation is needed to refine risk scores in this patient population.     

Performance of stent thrombosis and bleeding risk scores in out-of-hospital cardiac arrest due to acute coronary syndromes

BackgroundPatients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated.MethodsAll consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores.ResultsAmong 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05; P = 0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88–0.98; P = 0.010 and OR 0.61; 95% CI 0.41–0.89; P = 0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18–3.73; P = 0.011) were independent risk factors for major bleeding.ConclusionThe classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population.     

Riesgo hemorrágico y embólico de los pacientes con fibrilación auricular y cáncer

Introduction and objectivesThe impact of cancer on clinical outcomes in patients with atrial fibrillation (AF) is unclear. The aim of this study was to assess how cancer influences the prediction and risk of embolic and hemorrhagic events in patients with AF.MethodsThe study population comprised 16 056 patients from a Spanish health area diagnosed with AF between 2014 and 2018. Of these, 1137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years, we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis, considering death as a competing risk.ResultsNo association was detected between an increased risk of embolic events and cancer overall (sHR, 0.73; 95%CI, 0.41-1.26), active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding, although only in patients with active cancer (sHR, 1.42; 95%CI, 1.20-1.67) or prior radiotherapy (sHR, 1.40; 95%CI, 1.19-1.65). Both the CHA₂DS₂-VASc and HAS-BLED scores showed suboptimal performance to predict embolic and bleeding risk (c-statistic < 0.50), respectively, in nonanticoagulated patients with active cancer. The ratio between the increase in bleeding and the decrease in embolisms with anticoagulation was similar in patients with and without cancer (5.6 vs 7.8; P < .001).ConclusionsCancer was not associated with an increased risk of embolic events in AF patients, only with an increased risk of bleeding. However, active cancer worsened the ability of the CHA₂DS₂-VASc and HAS-BLED scores to predict embolic and bleeding events, respectively, in nonanticoagulated patients.Full English text available from:www.revespcardiol.org/en     

Comparison of clinical performance of four gastrointestinal bleeding risk scores in Chinese patients with atrial fibrillation receiving oral anticoagulants

Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers—the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3?±?11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576–0.728), 0.862 (95% CI 0.809–0.914), 0.606 (95% CI 0.527–0.685), and 0.873 (95% CI 0.816–0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.

     

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

IntroductionPatients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis.MethodsConsecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course.Results1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p < 0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p < 0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p < 0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02–229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03–2.06), with no differences in major bleeding rate.ConclusionConcomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations.     

The Impact of CHA2DS2-VASc and HAS-BLED Scores on Clinical Outcomes in the Amplatzer Amulet Study

ObjectivesThe aim of this study was to evaluate the impact of CHA₂DS₂-VASc and HAS-BLED scores on ischemic and bleeding events of patients enrolled in the Amplatzer Amulet Observational Study.BackgroundBaseline CHA₂DS₂-VASc and HAS-BLED scores have been validated in atrial fibrillation patients to guide about anticoagulation but not in patients treated by left atrial appendage occlusion (LAAO).MethodsSubjects were stratified according to CHA₂DS₂-VASc and HAS-BLED scores. Clinical outcomes were collected through 2 years and adjudicated by an independent committee.ResultsSubjects were considered at low (n = 156), moderate (n = 715), and high (n = 215) risk for ischemic stroke, corresponding to CHA₂DS₂-VASc scores of <3, 3 to 5, and ≥6, respectively. The annual rates of ischemic stroke were 1.1%, 2.0%, and 3.5%, respectively. When compared with the predicted rate, LAAO reduced the risk of ischemic stroke by 56%, 69%, and 68%. Device-related thrombus occurred in 0.7%, 1.5%, and 3.0% of subjects at low, moderate, and high risk for ischemic stroke, respectively. The HAS-BLED score was ≤3 in 629 subjects and >3 in 456 subjects, respectively. Non-peri-procedural major bleeding was reduced by 11% and 9% compared with predicted rates in the low and high bleeding risk groups, respectively.ConclusionsLAAO with the Amplatzer Amulet reduced the risk of ischemic stroke compared with the predicted rate, with a greater magnitude among patients at high thromboembolic risk without increasing the bleeding risk. (Amplatzer™Amulet™ Post-Market Study [Amulet™PMS]; NCT02447081)     

Stroke and Bleeding Risk Co-distribution in Real-world Patients with Atrial Fibrillation: The Euro Heart Survey

BackgroundThe choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely on cardioembolic and bleeding risk stratification. Sharing some risk factors, schemes to predict thrombotic and bleeding risk are expected not to be independent, yet the degree of their association has never been clearly quantified.MethodsWe described the cardioembolic (Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack [CHADS₂]/Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack, Vascular disease, Age 65-75, Sex category i.e. females [CHA₂DS₂-VASc]) and bleeding risk (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly [HAS-BLED]) co-distribution among patients of the Euro Heart Survey on atrial fibrillation. We measured the within-patient correlation (Spearman) and concordance between the 2 types of score and score-based risk categorization (low, intermediate, high). The score-based predicted risk co-classification was then related to the observed 1-year stroke and bleeding occurrence.ResultsIn 3920 patients, we found a between-scores correlation of 0.416 (P < .001) between HAS-BLED and CHADS₂, and 0.512 (P < .001) between HAS-BLED and CHA₂DS₂-VASc. In 89% (CHADS₂/HAS-BLED) and 97% (CHA₂DS₂-VASc/HAS-BLED) of patients, the bleeding risk category was equal to or lower than their cardioembolic risk category (P < .001 for symmetry test). A complete concordance between risk categories was found in 39.6% (CHADS₂/HAS-BLED) and 21.7% (CHA₂DS₂-VASc/HAS-BLED) of patients; 4.4% (CHADS₂/HAS-BLED) and 7.7% (CHA₂DS₂-VASc/HAS-BLED) of patients had high cardioembolic risk/low bleeding risk or vice versa. A tendency for an increasing frequency of stroke was observed for increasing bleeding risk within cardioembolic risk categories and vice versa.ConclusionsIn a real-world population with atrial fibrillation, we confirmed that the cardioembolic and bleeding risk classifications are correlated but not exchangeable. It is then worth verifying the advantages of a strategy adopting a combined risk assessment over a strategy relying only on the cardioembolic risk evaluation.     

Is prognostic nutritional index a predictive marker for estimating all-cause in-hospital mortality in COVID-19 patients with cardiovascular risk factors?

BackgroundThis study examined the possible association between the prognostic nutritional index (PNI) and in-hospital mortality rates in cases with a high cardiovascular risk burden and hospitalized with the diagnosis of coronavirus disease 2019 (COVID-19).Material and MethodsThis retrospective and cross-sectional study included 294 COVID-19 patients hospitalized in a tertiary referral pandemic center. The study cohort was grouped into tertiles based on the initial PNI values as T1, T2, and T3. The PNI was calculated for each case and the prognostic value of this index was compared to CURB-65 and 4C mortality risk scores in predicting in-hospital mortality.ResultsPatients stratified into the T1 tertile had a lower lymphocyte count, serum albumin level, and PNI values. In a multivariate analysis, the PNI (OR: 0.688,%95CI: 0.586–0.808, p < 0.001) was an independent predictor for all-cause in-hospital death. After adjusting for confounding independent parameters, patients included in the T1 tertile were found to have 11.2 times higher rates of in-hospital mortality compared to the T3 group, which was presumed as the reference group. In addition, we found that the area under curve (AUC) value of PNI was significantly elevated than that of serum albumin level and total lymphocyte counts alone. [(AUC):0.79 vs AUC:0.75 vs AUC:0.69; respectively).ConclusionThis study demonstrated that the PNI is independently related with in-hospital mortality in patient with COVID-19 and cardiovascular risk factors. The power of the PNI was also validated using well-accepted risk scores of COVID-19 such as CURB-65 and 4C mortality risk scores.     

Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding scores in ACS patients undergoing PCI: insights from a cohort of 4939 patients in China

Background The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models'' population limits simple extrapolation to other local population. We aimed to compare the performance of the three risk models in Chinese patients. Methods We evaluated the performance of the three predicting scores for predicting in-hospital major bleeding events defined by thrombolysis in myocardial infarction (TIMI) serious (major and minor) episodes, in a cohort of Chinese ACS patients with either non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI). Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive accuracy of the risk scores by the Delong non-parametric test. Results TIMI serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS, respectively). The CRUSADE, ACTION and ACUTIY-HORIZONS scores showed an adequate discriminatory capacity for major bleeding: in overall patients, the C-statistic was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was 0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91, 0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was significantly lower than those of the CRUSADE and ACTION scores for the prediction of TIMI serious bleeding in overall patients (compared with CRUSADE, z = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P = 0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02; compared with ACTION, z = 7.91, P = 0.002). No differences were observed when the CRUSADE and ACTION models were compared to each other, regardless of overall patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P = 0.60), and STEMI patients (z = 0.36, P= 0.74). However, the three risk scores all overestimated the absolute major bleeding risk in each risk stratification in our study. For example, the predicted rate of CRUSADE score at high risk stratification was 11.9% vs. an actual rate of 5.3%. Conclusions The CRUSADE and ACTION scores had a greater calibration and discrimination for in-hospital major bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS undergoing PCI. However, they all overestimated the bleeding risk rate for Chinese populations. Calibration of these risk scores would be useful for the generalization in Chinese populations.