RESUMEN
BACKGROUND: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS. METHODS: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19â826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC). FINDINGS: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding. INTERPRETATION: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making. FUNDING: None.
Asunto(s)
Síndrome Coronario Agudo/complicaciones , Conjuntos de Datos como Asunto , Aprendizaje Automático , Mortalidad , Complicaciones Posoperatorias , Adulto , Toma de Decisiones Clínicas , Femenino , Hemorragia/etiología , Humanos , MasculinoRESUMEN
BACKGROUND: There is scarce information on the prognostic role of frailty and atrial fibrillation (AF) in elderly patients with acute coronary syndrome (ACS). METHODS: The aim was to analyse the management of elderly patients with frailty and AF who suffered an ACS using data of the prospective multicentre LONGEVO-SCA registry. We evaluated the predictive performance of FRAIL, Charlson scores and AF status for adverse events at 6-month follow-up. RESULTS: A total of 531 unselected patients with ACS and above 80 years old [mean age 84.4 (SD = 3.6) years; 322 (60.6%) male] were enrolled, of whom 128 (24.1%) with AF and 145 (27.3%) with frailty. Mutually exclusive number of patients were as follows: non-frail and sinus rhythm (SR) 304 (57.2%); frail and SR 99 (18.6%); non-frail and AF 82 (15.4%); and frail and AF 46 (8.7%). Frail and AF patients compared with non-frail and SR patients had higher risk of all-cause mortality [HR 2.61, (95% CI 1.28-5.31; P = .008)], readmissions [HR 2.28, (95%CI 1.37-3.80); P = .002)] and its composite [HR 2.28, (95% CI 1.44-3.60); P < .001)]. After multivariate adjustment, FRAIL score [HR 1.41, (95% CI 1.02-1.97); P = .040] and Charlson index [HR 1.32, (95% CI 1.09-1.59); P = .003] were significantly associated with mortality. AF status was not independently related with adverse events. CONCLUSIONS: Frailty but not AF status was independently associated with follow-up adverse events. Frailty status and high Charlson index were independent conditions associated with adverse events during the follow-up. The impact of functional status has a bigger prognostic role over AF status in elderly patients with ACS.
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Síndrome Coronario Agudo/terapia , Fibrilación Atrial/epidemiología , Fragilidad/epidemiología , Mortalidad , Readmisión del Paciente/estadística & datos numéricos , Síndrome Coronario Agudo/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/mortalidad , Disfunción Cognitiva , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Estado Funcional , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Revascularización Miocárdica , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/epidemiologíaRESUMEN
PURPOSE: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population. METHODS: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis. RESULTS: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding. CONCLUSION: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.
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Síndrome Coronario Agudo/terapia , Clopidogrel/uso terapéutico , Intervención Coronaria Percutánea/estadística & datos numéricos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Anciano , Anciano de 80 o más Años , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Infarto del Miocardio/epidemiología , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Puntaje de Propensión , Sistema de Registros , Estudios Retrospectivos , Ticagrelor/administración & dosificación , Ticagrelor/efectos adversosRESUMEN
BACKGROUND: CHA2 DS2 -VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). We sought to study if this score predicts outcomes in elderly patients with Non-ST segment Elevation Acute Coronary Syndromes (NSTEACS). METHODS: The multicenter LONGEVO-SCA prospective registry included 532 unselected patients with NSTEACS aged ≥80 years. Data to calculate CHA2 DS2 -VASc Score were available in 523 patients (98.3%). They were classified according to CHA2 DS2 -VASc Score: group 1 (score ≤ 4), and 2 (5-9). We studied outcomes in terms of mortality or readmission at 6 months follow-up. RESULTS: A total of 266 patients (51%) had a high CHA2 DS2 -VASc Score (group 2). They were more often women, with more cardiovascular risk factors, such as hypertension or diabetes mellitus, and history of previous stroke and cardiovascular disease and heart failure (all, P = .001). Geriatric syndromes (Barthel Index, Lawton Brody, cognitive impairment, and frailty) and Charlson Index were worse in this group (all, P = .001). They had poorer clinical status on admission, with worse Killip class and lower left ventricle ejection fraction (all, P = .001), and developed new-onset AF more often during admission (12.4% vs. 6.6%, P = .024). At six months follow-up, patients in group 2 had higher reinfarction, all-cause mortality, and mortality or readmission rates. A CHA2 DS2 -VASc Score > 4 was associated with mortality or readmission at 6 months (HR 2.07, P < .001). However, after adjusting for potential confounders, this last association was not significant (P = .175). CONCLUSIONS: A CHA2 DS2 -VASc Score > 4 is present in half of octogenarians with NSTEACS and is associated with poorer outcomes. However, it is not an independent predictor of events and should not replace recommended tools for risk prediction in this setting.
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Síndrome Coronario Agudo , Fibrilación Atrial , Accidente Cerebrovascular , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Anciano , Anciano de 80 o más Años , Anticoagulantes , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Femenino , Humanos , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (Pâ¯=â¯.886). In the first 2â¯weeks ADIR was higher than ADBR (Pâ¯=â¯.013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (Pâ¯=â¯.003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (Pâ¯=â¯.012 and Pâ¯=â¯.022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1â¯year after PCI. ADIR was greater than ADBR in the first 2â¯weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.
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Síndrome Coronario Agudo/terapia , Hemorragia/epidemiología , Isquemia/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Complicaciones Posoperatorias/epidemiología , Anciano , Clopidogrel/uso terapéutico , Femenino , Hemorragia/etiología , Humanos , Isquemia/etiología , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complicaciones Posoperatorias/etiología , Clorhidrato de Prasugrel/uso terapéutico , Recurrencia , Sistema de Registros , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/terapia , Ticagrelor/efectos adversos , Ticagrelor/uso terapéutico , Factores de TiempoRESUMEN
AIMS: Nutrition is an important determinant of health above the age of 80 years. Malnutrition in the elderly is often underdiagnosed. The aim of this study was to report the prevalence and prognostic value of malnutrition in patients ≥80 years old with atrial fibrillation (AF) with and without anticoagulant therapy. METHODS AND RESULTS: We assessed the nutritional status of 4724 octogenarian patients with diagnoses of AF in a single centre from Spain between 2014 and 2017 with the CONUT score. Malnutrition was confirmed in 2036 patients (43.1%). Anticoagulation prescription was more frequent in patients with good nutrition than in those malnourished (79.5% vs. 71.7%, P < 0.001). The impact of malnutrition on mortality was evaluated by Cox regression, whereas its association with ischaemic stroke and major bleeding was studied through competing risk analysis. After multivariate adjusting, malnutrition was associated with mortality [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.24-1.49], stroke [sub-distribution HR (sHR) 1.37, 95% CI 1.10-1.69], and major bleeding (sHR 1.29, 95% CI 1.02-1.64). In anticoagulated patients, the embolic-haemorrhagic trade-off event was virtually neutral for those who had normal nutritional status [average daily rates (ADRs) for stroke and bleeding: 4.70 and 4.69 per 100 000 patients/day, respectively; difference = +0.01 per 100 000 patients/day; P = 0.99] and negative for those with malnutrition (ADR for stroke and bleeding: 5.38 and 7.61 per 100 000 patients/day, respectively; difference = -2.23 per 100 000 patients/day; P = 0.07). CONCLUSION: Malnutrition is very common in octogenarian patients with AF, being a clinical predictor for poor prognosis. For anticoagulated patients, malnutrition was associated with a negative embolic-haemorrhagic balance.
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Fibrilación Atrial , Isquemia Encefálica , Desnutrición , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Hemorragia/epidemiología , Humanos , Desnutrición/diagnóstico , Desnutrición/epidemiología , Factores de Riesgo , España , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: Statins are recommended for secondary prevention. Our aims were to describe the proportion of very elderly patients receiving statins after non-ST segment elevation acute coronary syndrome (NST-ACS) and to determine the prognostic implications of statins use. METHODS: This prospective registry was performed in 44 hospitals that included patients ≥80 years discharged after a NST-ACS from April 2016 to September 2016. RESULTS: We included 523 patients, the mean age was 84.2 ± 4.0 years and 200 patients (38.2%) were women. Previous statin treatment was recorded in 282 patients (53.4%), and 135 (32.5%) had LDL cholesterol levels >2.6 mmol/L. Mean LDL cholesterol levels during admission were 2.3 ± 0.9 mmol/L. Statins were prescribed at discharge to 474 patients (90.6%). Compared with patients discharged on statins, those that did not receive statins were more often frail (22 [47.8%] vs. 114 [24.4%], p < 0.01) and underwent an invasive approach less frequently (30 [61.2%] vs. 374 [78.9%], p = 0.01). During a 6-month follow-up, 50 patients died (9.5%). There was a nonsignificant trend to higher mortality in patients not treated with statins (6 [15%] vs. 44 [9.6%], p = 0.30), but statins were not independently associated with lower mortality (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.30-2.11, p = 0.65), nor with a reduction in the combined endpoint mortality/hospitalizations (HR 0.89; 95% CI 0.52-1.55, p = 0.69). CONCLUSIONS: Although most octogenarians presenting a NST-ACS are already on statins before the episode, their LDL cholesterol is frequently >2.6 mmol/L. Octogenarians who do not receive statins have a high-risk profile, with significant frailty and comorbidity.
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Síndrome Coronario Agudo/mortalidad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio sin Elevación del ST/mortalidad , Síndrome Coronario Agudo/terapia , Anciano de 80 o más Años , LDL-Colesterol/sangre , Comorbilidad , Femenino , Estudios de Seguimiento , Anciano Frágil , Humanos , Masculino , Infarto del Miocardio sin Elevación del ST/terapia , Alta del Paciente , Pronóstico , Estudios Prospectivos , Sistema de Registros , España/epidemiologíaRESUMEN
BACKGROUND: The magnitude of the association between diabetes (DM) and outcomes in elderly patients with acute coronary syndromes (ACS) is controversial. No study assessed the prognostic impact of DM according to frailty status in these patients. METHODS: The LONGEVO-SCA registry included unselected ACS patients aged ≥ 80 years. Frailty was assessed by the FRAIL scale. We evaluated the impact of previous known DM on the incidence of death or readmission at 6 months according to status frailty by the Cox regression method. RESULTS: A total of 532 patients were included. Mean age was 84.3 years, and 212 patients (39.8%) had previous DM diagnosis. Patients with DM had more comorbidities and higher prevalence of frailty (33% vs 21.9%, p = 0.002). The incidence of death or readmission at 6 months was higher in patients with DM (HR 1.52, 95% CI 1.12-2.05, p 0.007), but after adjusting for potential confounders this association was not significant. The association between DM and outcomes was not significant in robust patients, but it was especially significant in patients with frailty [HR 1.72 (1.05-2.81), p = 0.030, p value for interaction = 0.049]. CONCLUSIONS: About 40% of elderly patients with ACS had previous known DM diagnosis. The association between DM and outcomes was different according to frailty status.
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Síndrome Coronario Agudo/mortalidad , Diabetes Mellitus/mortalidad , Fragilidad/mortalidad , Anciano de 80 o más Años , Estudios de Casos y Controles , Comorbilidad , Femenino , Fragilidad/diagnóstico , Humanos , Incidencia , Masculino , Readmisión del Paciente/estadística & datos numéricos , Prevalencia , Estudios Prospectivos , Sistema de RegistrosRESUMEN
KEY POINTS: Two-pore channels (TPCs) were identified as a novel family of endolysosome-targeted calcium release channels gated by nicotinic acid adenine dinucleotide phosphate, as also as intracellular Na(+) channels able to control endolysosomal fusion, a key process in autophagic flux. Autophagy, an evolutionarily ancient response to cellular stress, has been implicated in the pathogenesis of a wide range of cardiovascular pathologies, including heart failure. We report direct evidence indicating that TPCs are involved in regulating autophagy in cardiomyocytes, and that TPC knockout mice show alterations in the cardiac lysosomal system. TPC downregulation implies a decrease in the viability of cardiomyocytes under starvation conditions. In cardiac tissues from both humans and rats, TPC transcripts and protein levels were higher in females than in males, and correlated negatively with markers of autophagy. We conclude that the endolysosomal channels TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts. ABSTRACT: Autophagy participates in physiological and pathological remodelling of the heart. The endolysosomal two-pore channels (TPCs), TPC1 and TPC2, have been implicated in the regulation of autophagy. The present study aimed to investigate the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. In cultured cardiomyocytes, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagy identified by increased LC3-II and decreased p62 levels. Small interfering RNA depletion of TPC2 alone or together with TPC1 increased both LC3II and p62 levels under basal conditions and in response to serum starvation, suggesting that, under conditions of severe energy depletion (serum plus glucose starvation), changes in the autophagic flux (as assessed by use of bafilomycin A1) occurred either when TPC1 or TPC2 were downregulated. The knockdown of TPCs diminished cardiomyocyte viability under starvation and simulated ischaemia. Electron micrographs of hearts from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild-type mice. In cardiac tissues from humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males. Furthermore, transcript levels of TPCs correlated negatively with p62 levels in heart tissues. TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes (i.e. there is a negative effect on cell viability under stress conditions in their absence) and they are differentially expressed in male and female human and murine hearts, where they correlate with markers of autophagy.
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Autofagia/fisiología , Canales de Calcio/fisiología , Lisosomas/fisiología , Miocitos Cardíacos/fisiología , Caracteres Sexuales , Anciano , Animales , Animales Recién Nacidos , Apéndice Atrial/fisiología , Células Cultivadas , Femenino , Humanos , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ratas , Ratas Sprague-DawleyRESUMEN
The receiver-operating characteristic (ROC) curve is the most widely used measure for evaluating the performance of a diagnostic biomarker when predicting a binary disease outcome. The ROC curve displays the true positive rate (or sensitivity) and the false positive rate (or 1-specificity) for different cut-off values used to classify an individual as healthy or diseased. In time-to-event studies, however, the disease status (e.g. death or alive) of an individual is not a fixed characteristic, and it varies along the study. In such cases, when evaluating the performance of the biomarker, several issues should be taken into account: first, the time-dependent nature of the disease status; and second, the presence of incomplete data (e.g. censored data typically present in survival studies). Accordingly, to assess the discrimination power of continuous biomarkers for time-dependent disease outcomes, time-dependent extensions of true positive rate, false positive rate, and ROC curve have been recently proposed. In this work, we present new nonparametric estimators of the cumulative/dynamic time-dependent ROC curve that allow accounting for the possible modifying effect of current or past covariate measures on the discriminatory power of the biomarker. The proposed estimators can accommodate right-censored data, as well as covariate-dependent censoring. The behavior of the estimators proposed in this study will be explored through simulations and illustrated using data from a cohort of patients who suffered from acute coronary syndrome.
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Modelos Estadísticos , Curva ROC , Estadísticas no Paramétricas , Síndrome Coronario Agudo/diagnóstico , Biomarcadores/análisis , Bioestadística , Simulación por Computador , Reacciones Falso Positivas , Humanos , Valor Predictivo de las Pruebas , Análisis de Supervivencia , Factores de TiempoRESUMEN
Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.
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Síndrome Coronario Agudo/tratamiento farmacológico , Isquemia/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Humanos , Intervención Coronaria Percutánea , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIMS: Clinicians need to get better at identifying patients who would have poor quality of anticoagulation control with vitamin-K antagonists (VKAs). We assessed the predictive ability of SAMe-TT2R2 score, recently conceived for the prior purpose, and examined its relationship with major bleeding, thromboembolic (TE) complications, and death. METHODS AND RESULTS: Retrospectively, 911 consecutive patients with non-valvular atrial fibrillation (NVAF) started on VKAs within 8 months were studied. The percentage of international normalized ratios in therapeutic range (PINRR) at different levels was used as a metric of anticoagulation quality. We also tested the SAMe-TT2R2 predictability for major bleeding, TE complications, and death throughout 10 ± 3 months. The PINRR decreased from 62% at zero point to 53% at ≥4 points of SAMe-TT2R2. 82.1% of patients who achieved PINRR ≥ 70% had 0 or 1 point of SAMe-TT2R2. SAMe-TT2R2 performed significantly better at PINRR 70% than at 65 and 60% (c-statistic = 0.60 vs. c-statistic = 0.56). The calibration of SAMe-TT2R2 was excellent (Hosmer-Lemeshow test P-values ≥ 0.6). SAMe-TT2R2 showed significant association with the composite outcome of major bleeding, TE complications, and death [n = 98; hazard ratio (HR) = 1.32; 95% confidence interval (CI) 1.08-1.60]; the c-statistic was 0.57 (95% CI: 0.51-0.62) and P = 0.03. As individual outcomes, SAMe-TT2R2 was significantly associated with death (n = 60; HR = 1.3; 95% CI: 1.03-1.69), but not with either major bleeding (n = 30; HR = 1.2; 95% CI: 0.85-1.76) or TE complications (n = 15; HR = 1.01; 95% CI: 0.58-1.77). CONCLUSION: Among NVAF patients, SAMe-TT2R2 could represent a useful clinical tool to identify patients who would have poor quality of anticoagulation control with VKAs. SAMe-TT2R2 successfully predicts the composite outcome of major bleeding, TE complications, and death.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Coagulación Sanguínea/efectos de los fármacos , Técnicas de Apoyo para la Decisión , Accidente Cerebrovascular/prevención & control , Tromboembolia/prevención & control , Vitamina K/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Monitoreo de Drogas/métodos , Femenino , Hemorragia/inducido químicamente , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Tromboembolia/sangre , Tromboembolia/diagnóstico , Tromboembolia/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Accurate risk stratification is considered the first and most important step in the management of patients with non-valvular atrial fibrillation (NVAF). We compared the performance of the widely used CHA2DS2-VASc and the recently developed R2CHADS2 and ATRIA scores, for predicting thromboembolic (TE) event in either non-anticoagulated or anticoagulated patients with NVAF. METHODS: The non-anticoagulated cohort was comprised of 154 patients, whereas 911 patients formed the cohort of patients on vitamin-K-antagonist. The scores were computed using the criteria mentioned in their developmental cohorts. Measures of performance for the risk scores were evaluated at predicting TE event. RESULTS: In the non-anticoagulated cohort, 9 TE events occurred during 11 ± 2.7 months. CHA2DS2-VASc showed significant association with TE occurrence: hazard ratio (HR) = 1.58 (95 % confidence interval [95 % IC] 1.01-2.46), but R2CHADS2 and ATRIA did not (HR = 1.23 (95 % CI 0.86-1.77) and 1.20 (95 % CI 0.93-1.56), respectively. In the anticoagulated cohort, after 10 ± 3 months of follow up, 18 TE events were developed. In that cohort, the three scores showed similar association with TE risk: HR = 1.49 (95 % CI 1.13-1.97), 1.41 (95 % CI 1.13-1.77) and 1.37 (95 % CI 1.12-1.66) for CHA2DS2-VASc, R2CHADS2 and ATRIA, respectively. In both cohorts, no TE event occurred in patients classified in the low risk category according to CHA2DS2-VASc or R2CHADS2. CONCLUSIONS: In this study of NVAF patients, CHA2DS2-VASc has better association with TE events than the new R2CHADS2 and ATRIA risk scores in the non-anticoagulated cohort. CHA2DS2-VASc and R2CHADS2 can identify patients at truly low risk regardless of the anticoagulation status.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Medición de Riesgo/métodos , Tromboembolia/etiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia/prevención & controlRESUMEN
BACKGROUND: Recently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. METHODS: We studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. RESULTS: There were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively). Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores. In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. CONCLUSIONS: The new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04364516.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Hemorragia , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Masculino , Femenino , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/diagnóstico , Anciano , Medición de Riesgo/métodos , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Estudios de Seguimiento , Persona de Mediana Edad , Anciano de 80 o más Años , Factores de Riesgo , Administración Oral , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.
Asunto(s)
Antagonistas Adrenérgicos beta , Fibrilación Atrial , Bloqueadores de los Canales de Calcio , Tasa de Filtración Glomerular , Frecuencia Cardíaca , Insuficiencia Renal Crónica , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/fisiopatología , Femenino , Masculino , Bloqueadores de los Canales de Calcio/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Anciano , Frecuencia Cardíaca/efectos de los fármacos , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Resultado del Tratamiento , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Riñón/fisiopatología , Factores de Riesgo , Estudios de SeguimientoRESUMEN
BACKGROUND: Diabetes mellitus (DM) increases the probability of presenting atrial fibrillation (AF) and it is a predictor of its ischemic stroke. There is limited information of the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or bleeding events in patients with pre-DM and AF. METHODS: To investigate whether the presence of pre-DM in patients with AF predicts ischemic or bleeding events, myocardial infarction or mortality, we performed a retrospective study with a final cohort of 2993 non-diabetic patients with AF and data of glycated hemoglobin (HbA1c). We divided the cohort in two groups: those with normal glucose (n = 1351) and those with pre-diabetes (n = 1642). Incidence rates were calculated as the number of events per 100 person-years and were then compared between groups. Competitive hazard regression analysis for non-fatal events(death as the competing event) and conventional Cox regression for mortality were performed. RESULTS: There was not difference between groups for incidence rates of the different events per 100 person-years. Even considering HbA1c as continuous variable, the unadjusted analysis showed no relation between levels of HbA1c and more risk of events. This association remained not significant after adjustment for CHA2DS2-VASc score, HAS-BLED score and anticoagulation therapy. CONCLUSION: In this study of 2993 non-diabetic patients with new-onset AF, we have not found an association between HbA1c and worse prognosis when it is in the range of pre-diabetes.
Asunto(s)
Fibrilación Atrial , Estado Prediabético , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Anciano , Estado Prediabético/epidemiología , Estado Prediabético/sangre , Estado Prediabético/diagnóstico , Persona de Mediana Edad , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Valor Predictivo de las Pruebas , Estudios de Cohortes , Incidencia , Factores de Riesgo , Anciano de 80 o más Años , Estudios de SeguimientoRESUMEN
INTRODUCTION AND OBJECTIVES: Atrial fibrillation (AF) is linked to heart failure (HF). However, little has been published on the factors that may precipitate the onset of HF in AF patients. We aimed to determine the incidence, predictors, and prognosis of incident HF in older patients with AF with no prior history of HF. METHODS: Patients with AF older than 80 years and without prior HF were identified between 2014 and 2018. RESULTS: A total of 5794 patients (mean age, 85.2±3.8 years; 63.2% women) were followed up for 3.7 years. Incident HF, predominantly with preserved left ventricular ejection fraction, developed in 33.3% (incidence rate, 11.5-100 people-year). Multivariate analysis identified 11 clinical risk factors for incident HF, irrespective of HF subtype: significant valvular heart disease (HR, 1.99; 95%CI, 1.73-2.28), reduced baseline left ventricular ejection fraction (HR, 1.92; 95%CI, 1.68-2.19), chronic pulmonary obstructive disease (HR, 1.59; 95%CI, 1.40-1.82), enlarged left atrium (HR 1.47, 95%CI 1.33-1.62), renal dysfunction (HR 1.36, 95%CI 1.24-1.49), malnutrition (HR, 1.33; 95%CI, 1.21-1.46), anemia (HR, 1.30; 95%CI, 1.17-1.44), permanent AF (HR, 1.15; 95%CI, 1.03-1.28), diabetes mellitus (HR, 1.13; 95%CI, 1.01-1.27), age per year (HR, 1.04; 95%CI, 1.02-1.05), and high body mass index for each kg/m2 (HR, 1.03; 95%CI, 1.02-1.04). The presence of incident HF nearly doubled the mortality risk (HR, 1.67; 95%CI, 1.53-1.81). CONCLUSIONS: The presence of HF in this cohort was relatively frequent and nearly doubled the mortality risk. Eleven risk factors for HF were identified, expanding the scope for primary prevention among elderly patients with AF.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Femenino , Anciano , Anciano de 80 o más Años , Masculino , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Incidencia , Volumen Sistólico , Función Ventricular Izquierda , Insuficiencia Cardíaca/tratamiento farmacológico , Factores de Riesgo , Pronóstico , Disfunción Ventricular Izquierda/complicacionesRESUMEN
BACKGROUND AND AIMS: Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients. METHODS: A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis. RESULTS: A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01-1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01-1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants. CONCLUSIONS: The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF.
Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Factores de Riesgo , Estudios de Cohortes , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Hemorragia/inducido químicamente , Anticoagulantes , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/inducido químicamenteRESUMEN
BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.