Impact of Right Ventricular Pacing in Patients With TAVR Undergoing Permanent Pacemaker Implantation.

BACKGROUND: Long-term right ventricular pacing (VP) has been related to negative left ventricular remodeling and heart failure (HF), but there is a lack of evidence regarding the prognostic impact on transcatheter aortic valve replacement (TAVR) patients. OBJECTIVES: The aim of the PACE-TAVI registry is to evaluate the association of high percentage of VP with adverse outcomes in patients with pacemaker implantation after TAVR. METHODS: PACE-TAVI is an international multicenter registry of all consecutive TAVR patients who underwent permanent pacemaker implantation for conduction disturbances in the first 30 days after the procedure. Patients were divided into 2 subgroups according to the percentage of VP (<40% vs ≥40%) at pacemaker interrogation. The primary endpoint was the composite of cardiovascular mortality or hospitalization for HF. RESULTS: A total of 377 patients were enrolled, 158 with VP <40% and 219 with VP ≥40%. After multivariable adjustment, VP ≥40% was associated with a higher incidence of the primary endpoint (HR: 2.76; 95% CI: 1.39-5.51; P = 0.004), first HF hospitalization (HR: 3.37; 95% CI: 1.50-7.54; P = 0.003), and cardiovascular death (HR: 3.77; 95% CI: 1.02-13.88; P = 0.04), while the incidence of all-cause death was not significantly different (HR: 2.17; 95% CI: 0.80-5.90; P = 0.13). Patients with VP ≥ 40% showed a higher New York Heart Association functional class both at 1 year (P = 0.009) and at last available follow-up (P = 0.04) and a nonsignificant reduction of left ventricular ejection fraction (P = 0.18) on 1-year echocardiography, while patients with VP <40% showed significant improvement (P = 0.009). CONCLUSIONS: In TAVR patients undergoing permanent pacemaker implantation, a high percentage of right VP at follow-up is associated with an increased risk for cardiovascular death and HF hospitalization. These findings suggest the opportunity to minimize right VP through dedicated algorithms in post-TAVR patients without complete atrioventricular block and to evaluate a more physiological VP modality in patients with persistent complete atrioventricular block.

Riesgo hemorrágico y embólico de los pacientes con fibrilación auricular y cáncer / Bleeding and embolic risk in patients with atrial fibrillation and cancer

Introducción y objetivos El impacto del cáncer en los eventos de los pacientes con fibrilación auricular (FA) no está claro. El objetivo de este estudio es evaluar cómo el cáncer influye en el riesgo de eventos embólicos y hemorrágicos de los pacientes con FA. Métodos Conformaron la población del estudio 16.056 pacientes de un área sanitaria española diagnosticados de FA entre 2014 y 2018. De ellos, 1.137 (7,1%) tenían antecedentes de cáncer. Durante una mediana de seguimiento de 4,9 años, se evaluó mediante un análisis de riesgos competitivos la relación entre el cáncer y las embolias y hemorragias. Resultados No se detectó asociación entre un mayor riesgo de eventos embólicos y cáncer en general (sHR=0,73; IC95%, 0,41-1,26). Sin embargo, el cáncer se asoció con un mayor riesgo hemorrágico, aunque solo en pacientes con cáncer activo (sHR=1,42; IC95%, 1,20-1,67) o radioterapia previa (sHR=1,40; IC95%, 1,19-1,65). Las escalas CHA2DS2-VASc y HAS-BLED mostraron un rendimiento subóptimo para predecir el riesgo, respectivamente, embólico y hemorrágico (estadístico c <0,50) de los pacientes no anticoagulados con cáncer activo. La relación entre el aumento de las hemorragias y la disminución de las embolias con anticoagulación fue similar en pacientes con y sin cáncer (5,6 frente a 7,8; p <0,001). Conclusiones El cáncer no se asoció con un mayor riesgo de eventos embólicos en pacientes con FA, solo con un mayor riesgo de hemorragia. Sin embargo, el cáncer activo empeoró la capacidad predictiva de las escalas CHA2DS2-VASc y HAS-BLED para predecir eventos en pacientes no anticoagulados (AU)

Introduction and objectives The 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. Methods The 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. Results No 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). Conclusions Cancer 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 (AU)

Bleeding and embolic risk in patients with atrial fibrillation and cancer.

INTRODUCTION AND OBJECTIVES: The 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. METHODS: The 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. RESULTS: No 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). CONCLUSIONS: Cancer 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.

Incidence and Predictors of Bleeding in Patients With Cancer and Atrial Fibrillation.

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p = 0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p = 0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p = 0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) scores were poor in patients with cancer (concordance statistic <0.6 and Brier score >0.1). In summary, cancer was associated with an increased risk of bleeding in patients with AF. The predictive ability of bleeding risk scores was poor in this population. Anticoagulation with vitamin K antagonist but not with direct oral anticoagulants, was an independent predictor of bleeding in patients with cancer.

A case report of cocaine abuse, acute coronary syndrome, and eroded plaque: stent or not stent?

BACKGROUND: Intracoronary imaging techniques have allowed characterizing atherosclerotic plaques morphologically in patients with the acute coronary syndrome (ACS). Although the main feature described is plaque rupture, the use of optical coherence tomography has made it possible to objectify that the eroded plaque is not uncommon in this setting. CASE SUMMARY: We presented a case of a 45-year-old man with active smoking and cocaine user, admitted to the emergency department for chest pain. The electrocardiogram showed ST-segment elevation myocardial infarction (STEMI) in the inferior leads. Emergent coronary angiography was performed, showing thrombotic occlusion of mid-distal right coronary artery. After successful thromboaspiration, no areas of significant angiographic stenosis were observed. Optical coherence tomography imaging at the occlusion site revealed an eroded plaque and a remaining small thrombusburden. Conservative management without stent implantation was decided. Treatments consisted of an acute phase glycoprotein IIb/IIIa inhibitor and subsequently dual antiplatelet therapy with Aspirin (ASA) and Ticagrelor 90 mg b.i.d. for 12 months. The patient remains asymptomatic and uneventful at 9-month follow-up. DISCUSSION: Young age, history of active smoking, and cocaine use are common clinical features in patients with ACS due to an eroded plaque. These patients frequently display a STEMI with the involvement of a single coronary vessel. Optical coherence tomography imaging aids to a precise diagnosis and to define a proper treatment.

New Cancer Diagnosis After Bleeding in Anticoagulated Patients With Atrial Fibrillation.

Background Bleeding is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulant therapy, and may be the first manifestation of underlying cancer. We sought to investigate to what extent bleeding represents the unmasking of an occult cancer in patients with AF treated with oral anticoagulants. Methods and Results Using data from CardioCHUVI-AF (Retrospective Observational Registry of Patients With Atrial Fibrillation From Vigo's Health Area), 8753 patients with AF aged ≥75 years with a diagnosis of AF between 2014 and 2017 were analyzed. Of them, 2171 (24.8%) experienced any clinically relevant bleeding, and 479 (5.5%) were diagnosed with cancer during a follow-up of 3 years. Among 2171 patients who experienced bleeding, 198 (9.1%) were subsequently diagnosed with cancer. Patients with bleeding have a 3-fold higher hazard of being subsequently diagnosed with new cancer compared with those without bleeding (4.7 versus 1.4 per 100 patient-years; adjusted hazard ratio [HR], 3.2 [95% CI, 2.6-3.9]). Gastrointestinal bleeding was associated with a 13-fold higher hazard of new gastrointestinal cancer diagnosis (HR, 13.4; 95% CI, 9.1-19.8); genitourinary bleeding was associated with an 18-fold higher hazard of new genitourinary cancer diagnosis (HR, 18.1; 95% CI, 12.5-26.2); and bronchopulmonary bleeding was associated with a 15-fold higher hazard of new bronchopulmonary cancer diagnosis (HR, 15.8; 95% CI, 6.0-41.3). For other bleeding (nongastrointestinal, nongenitourinary, nonbronchopulmonary), the HR for cancer was 2.3 (95% CI, 1.5-3.6). Conclusions In patients with AF treated with oral anticoagulant therapy, any gastrointestinal, genitourinary, or bronchopulmonary bleeding was associated with higher rates of new cancer diagnosis. These bleeding events should prompt investigation for cancers at those sites.

Impacto de la anticoagulación en los pacientes con demencia y fibrilación auricular. Resultados del registro CardioCHUVI-FA / Impact of anticoagulation in patients with dementia and atrial fibrillation. Results of the CardioCHUVI-FA registry

INTRODUCCIÓN Y OBJETIVOS: El envejecimiento de la población se asocia con una prevalencia creciente de fibrilación auricular (FA) y demencia. Con este estudio se pretende analizar el impacto de la anticoagulación oral en pacientes ancianos con FA y demencia de grado moderado-grave. MÉTODOS: Estudio retrospectivo unicéntrico que analiza a pacientes de edad ≥ 85 años con diagnóstico de FA entre 2013 y 2018. El impacto de la anticoagulación en la mortalidad, las embolias y las hemorragias se evaluó mediante un análisis multivariado de Cox. En los pacientes con demencia, dicho análisis se complementó con un propensity score matching en función de que se les prescribiera tratamiento anticoagulante o no. RESULTADOS: De los 3.549 pacientes de 85 o más años con FA, 221 presentaban demencia de grado moderado-grave (6,1%), de los que 88 (60,2%) fueron anticoagulados. Durante un seguimiento de 2,8 ±1,7 años, la anticoagulación se asoció con menor riesgo embólico y mayor riesgo hemorrágico tanto en pacientes con demencia (HRembolias=0,36; IC95%, 0,15-0,84; HRhemorragias=2,44; IC95%, 1,04-5,71) como sin demencia (HRembolias=0,58; IC95%, 0,45-0,74; HRhemorragias=1,55; IC95%, 1,21-1,98). Sin embargo, la anticoagulación únicamente se asoció con menor mortalidad en los pacientes sin demencia (HR=0,63; IC95%, 0,53-0,75), no en pacientes con demencia (HR ajustada=1,04; IC95%, 0,63-1,72; p = 0,541; HR después de propensity score matching=0,91; IC95%, 0,45-1,83; p = 0,785). CONCLUSIONES: En pacientes de 85 o más años con demencia moderada-grave y FA, la anticoagulación oral se asoció de manera significativa con menor riesgo de embolias y mayor riesgo hemorrágico, sin encontrarse diferencias en cuanto a mortalidad total

INTRODUCTION AND OBJECTIVES: Population aging is associated with an increased prevalence of atrial fibrillation (AF) and dementia. This study aimed to analyze the impact of oral anticoagulation in elderly patients with AF and moderate-severe dementia. METHODS: We conducted a single-center retrospective study analyzing patients aged ≥ 85 years with a diagnosis of AF between 2013 and 2018. The impact of anticoagulation on mortality, embolisms, and bleeding events was assessed by multivariate Cox analysis. In patients with dementia, this analysis was complemented by propensity score matching, depending on whether the patients were prescribed anticoagulant treatment or not. RESULTS: Of the 3549 patients aged ≥ 85 years with AF, 221 had moderate-severe dementia (6.1%), of whom 88 (60.2%) were anticoagulated. During a follow-up of 2.8 ±1.7 years, anticoagulation was associated with lower embolic risk and higher bleeding risk both in patients with dementia (hazard ratio [HR]embolisms, 0.36; 95%CI, 0,15-0.84; HRbleeding, 2.44; 95%CI, 1.04-5.71) and in those without dementia (HRembolisms, 5.58; 95%CI, 0.45-0.74; HRbleeding, 1.55, 95%CI, 1.21-1.98). However, anticoagulation was associated with lower mortality only in patients without dementia (HR, 0.63; 95%CI, 0.53-0.75) and not in those with dementia (adjusted HR, 1.04; 95%CI, 0.63-1.72; P=.541; HR after propensity score matching 0.91, 95%CI, 0.45-1.83; P=.785). CONCLUSIONS: In patients aged ≥ 85 years with moderate-severe dementia and AF, oral anticoagulation was significantly associated with a lower embolic risk and a higher bleeding risk, with no differences in total mortality

Usefulness of Bleeding After Acute Coronary Syndromes for Unmasking Silent Cancer.

There is a growing body of evidence on the incidence and negative prognostic impact of postdischarge hemorrhagic complications after an acute coronary syndrome (ACS). However, the risk of subsequent cancer after postdischarge bleeding in these patients is currently poorly known. The aim of this study was to assess the association of postdischarge bleeding with newly diagnosed cancers after an ACS. Data from a single-center registry of 3,644 ACS patients, who were discharged with dual antiplatelet therapy and treated with percutaneous coronary intervention, were used to investigate the association between postdischarge bleeding and diagnosis of cancer. During a median follow-up of 56.2 months, bleeding events were documented in 1,216 patients and newly diagnosed cancers in 227 patients. Postdischarge bleeding was associated with cancer diagnosis (adjusted hazard ratio [HR] 3.43, 95% confidence interval [CI] 2.62 to 4.50), but only spontaneous bleeding (adjusted HR 4.38, 95% CI 3.31 to 5.79). This association was stronger as the severity of the bleeding increased (HR 1.52, 4.88, 7.30, and 12.29, for BARC type 1, 2, 3a, and 3b bleeding, respectively). Positive predictive values for cancer diagnosis of postdischarge bleeding was 7.7%. Median time from bleeding to cancer was 4.6 months. In conclusion, spontaneous postdischarge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months. A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients.

Impact of malnutrition in the embolic-haemorrhagic trade-off of elderly patients with atrial fibrillation.

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.

Impact of anticoagulation in patients with dementia and atrial fibrillation. Results of the CardioCHUVI-FA registry.

INTRODUCTION AND OBJECTIVES: Population aging is associated with an increased prevalence of atrial fibrillation (AF) and dementia. This study aimed to analyze the impact of oral anticoagulation in elderly patients with AF and moderate-severe dementia. METHODS: We conducted a single-center retrospective study analyzing patients aged ≥ 85 years with a diagnosis of AF between 2013 and 2018. The impact of anticoagulation on mortality, embolisms, and bleeding events was assessed by multivariate Cox analysis. In patients with dementia, this analysis was complemented by propensity score matching, depending on whether the patients were prescribed anticoagulant treatment or not. RESULTS: Of the 3549 patients aged ≥ 85 years with AF, 221 had moderate-severe dementia (6.1%), of whom 88 (60.2%) were anticoagulated. During a follow-up of 2.8 ±1.7 years, anticoagulation was associated with lower embolic risk and higher bleeding risk both in patients with dementia (hazard ratio [HR]embolisms, 0.36; 95%CI, 0.15-0.84; HRbleeding, 2.44; 95%CI, 1.04-5.71) and in those without dementia (HRembolisms, 0.58; 95%CI, 0.45-0.74; HRbleeding, 1.55, 95%CI, 1.21-1.98). However, anticoagulation was associated with lower mortality only in patients without dementia (HR, 0.63; 95%CI, 0.53-0.75) and not in those with dementia (adjusted HR, 1.04; 95%CI, 0.63-1.72; P=.541; HR after propensity score matching 0.91, 95%CI, 0.45-1.83; P=.785). CONCLUSIONS: In patients aged ≥ 85 years with moderate-severe dementia and AF, oral anticoagulation was significantly associated with a lower embolic risk and a higher bleeding risk, with no differences in total mortality.

Impacto del bloqueo del sistema renina-angiotensina en el pronóstico del síndrome coronario agudo en función de la fracción de eyección / Impact of renin-angiotensin system blockade on the prognosis of acute coronary syndrome based on left ventricular ejection fraction

INTRODUCCIÓN Y OBJETIVOS: No está clara la asociación entre los inhibidores de la enzima de conversión de la angiotensina (IECA) o los antagonistas del receptor de la angiotensina II (ARA-II) y la mortalidad de los pacientes con síndrome coronario agudo (SCA) sometidos a intervención coronaria percutánea (ICP) con fracción de eyección del ventrículo izquierdo (FEVI) conservada. Nuestro objetivo es determinar dicha asociación en pacientes con FEVI conservada o reducida. MÉTODOS: Se analizaron datos procedentes del registro BleeMACS. El objetivo principal fue la mortalidad a 1 año. Se aplicaron ponderación por la probabilidad inversa del tiempo de supervivencia y ajustes por regresión de Cox, puntuación de propensión y variables instrumentales. RESULTADOS: De los 15.401 pacientes con SCA sometidos a ICP, se prescribieron IECA/ARA-II al 75,2%. Se produjeron 569 muertes (3,7%) durante el primer año tras el alta hospitalaria. Después del ajuste multivariado, los IECA/ARA-II se asociaron con menor mortalidad, pero solo en los pacientes con FEVI ≤ 40% (HR=0,62; IC95%, 0,43-0,90; p = 0,012). Con los IECA/ARA-II, la reducción del riesgo relativo de la mortalidad estimada fue del 46,1% en los pacientes con FEVI ≤ 40% y del 15,7% en aquellos con FEVI> 40% (pinteracción=0,008). En los pacientes con FEVI> 40%, los IECA/ARA-II se asociaron con menor mortalidad solo por infarto agudo de miocardio con elevación del segmento ST (HR=0,44; IC95%, 0,21-0.93; p = 0,031). CONCLUSIONES: El beneficio de los IECA/ARA-II en mortalidad tras ICP por SCA se concentra en pacientes con FEVI ≤ 40% y aquellos con FEVI> 40% e infarto agudo de miocardio con elevación del segmento ST. Se precisan estudios contemporáneos que analicen el impacto de los IECA/ARA-II en pacientes con SCA sin elevación del segmento ST y FEVI> 40%

INTRODUCTION AND OBJECTIVES: For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. METHODS: Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. RESULTS: Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P=.012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF> 40% (P value for treatment-by-LVEF interaction=.008). For patients with LVEF> 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P=.031). CONCLUSION: The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF> 40% and ST-segment elevation myocardial infarction. In non-ST-segment elevation-ACS patients with LVEF> 40%, further studies are needed to assess the prognostic impact of ACEI/ARB

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Impact of renin-angiotensin system blockade on the prognosis of acute coronary syndrome based on left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. METHODS: Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. RESULTS: Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P=.012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF> 40% (P value for treatment-by-LVEF interaction=.008). For patients with LVEF> 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P=.031). CONCLUSION: The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF> 40% and ST-segment elevation myocardial infarction. In non-ST-segment elevation-ACS patients with LVEF> 40%, further studies are needed to assess the prognostic impact of ACEI/ARB.

Incidence, predictors and prognostic impact of intracranial bleeding within the first year after an acute coronary syndrome in patients treated with percutaneous coronary intervention.

BACKGROUND: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003-2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine-Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. RESULTS: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7-319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01-1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36-8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. CONCLUSION: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

Vitamin K Antagonists and Direct Oral Anticoagulants in Nonagenarian Patients With Atrial Fibrillation.

OBJECTIVES: Nonagenarian patients are underrepresented in clinical trials that have evaluated oral anticoagulation in patients with atrial fibrillation (AF). The aim of this study was to assess the pronostic impact of oral anticoagulation in patients with AF age ≥90 years. DESIGN: Retrospective multicenter study of nonagenarian patients with AF. SETTING AND PARTICIPANTS: A total of 1750 nonagenarian inpatients and outpatients with nonvalvular AF between January 2013 and December 2018 in 3 Spanish health areas were studied. METHODS: Patients were divided into 3 groups based on antithrombotic therapy: nonoral anticoagulants (30.5%), vitamin-K antagonists (VKAs; 28.6%), and direct oral anticoagulants (DOACs; 40.9%). During a mean follow-up of 23.6 ± 6.6 months, efficacy outcomes (death and embolic events) were evaluated using a Cox regression analysis and safety outcomes (bleeding requiring hospitalization) by competing-risk regression. Results were complemented with a propensity score matching analysis. RESULTS: During follow-up, 988 patients died (56.5%), 180 had embolic events (10.3%), and 186 had major bleeding (10.6%). After multivariable adjustment, DOACs were associated with a lower risk of death and embolic events than nonanticoagulation [hazard ratio (HR) 0.75, 95% confidence interval (CI)] 0.61‒0.92), but VKAs were not (HR 0.87, 95% CI 0.72‒1.05). These results were confirmed after propensity score matching analysis. For bleeding, both DOACs and VKAs proved to be associated with a higher risk (HR for DOAC 1.43; 95% CI 0.97‒2.13; HR for VKA 1.94; 95% CI 1.31‒2.88), although findings for DOACs were not statistically significant (P = .074). For intracranial hemorrhage (ICH), only VKAs-not DOACs-presented a higher risk of ICH (HR 4.43; 95% CI 1.48‒13.31). CONCLUSIONS AND IMPLICATIONS: In nonagenarian patients with AF, DOACs led to a reduction in mortality and embolic events in comparison with nonanticoagulation. This reduction was not observed with VKAs. Although both DOACs and VKAs increased the risk of bleeding, only VKAs were associated with higher ICH rates.

Incidencia anual de trombosis del stent confirmadas y factores clínicos predictores en pacientes con SCA tratados con ticagrelor o prasugrel / Annual incidence of confirmed stent thrombosis and clinical predictors in patients with ACS treated with ticagrelor or prasugrel

Introducción y objetivos: Hay muy poca evidencia sobre las tasas de trombosis del stent (TS) en pacientes que reciben tratamiento antiagregante plaquetario doble (TAPD) con ticagrelor o prasugrel. El objetivo de este estudio es analizar la incidencia y predictores de la TS tras un síndrome coronario agudo en pacientes que reciben TAPD con ticagrelor frente a prasugrel. Métodos: Se utilizaron datos del registro RENAMI (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), y se analizó en total a 4.123 pacientes con síndrome coronario agudo dados de alta con TAPD con ticagrelor o prasugrel en 11 centros de 6 países europeos. Se consideró como evento la TS confirmada en el primer año. Se realizó un análisis de riesgos competitivos mediante un modelo de regresión de Fine y Gray, siendo la muerte el evento competitivo. Resultados: Recibieron TAPD con ticagrelor 2.604 pacientes y con prasugrel, 1.519; 41 pacientes (1,10%) presentaron TS, con incidencias acumuladas similares entre ticagrelor (1,21%) y prasugrel (0,90%). Los predictores independientes de la TS fueron: la edad (sHR = 1,03; IC95%, 1,01-1,06), la elevación del segmento ST (sHR = 2,24; IC95%, 1,22-4,14), el antecedente de infarto de miocardio (sHR = 2,56; IC95%, 1,19-5,49) y la creatinina sérica (sHR = 1,29; IC95%, 1,08-1,54). Conclusiones: La TS es infrecuente en pacientes que reciben TAPD con ticagrelor y prasugrel. La edad avanzada, la elevación del segmento ST, el antecedente de infarto y la creatinina sérica son las variables que se asocian con mayor riesgo de TS

Introduction and objectives: There is little evidence on rates of stent thrombosis (ST) in patients receiving dual antiplatelet therapy (DAPT) with ticagrelor or prasugrel. The aim of this study was to analyze the incidence and predictors of ST after an acute coronary syndrome among patients receiving DAPT with ticagrelor vs prasugrel. Methods: We used data from the RENAMI registry (REgistry of New Antiplatelet therapy in patients with acute Myocardial Infarction), analyzing a total of 4123 acute coronary syndrome patients discharged with DAPT with ticagrelor or prasugrel in 11 centers in 6 European countries. The endpoint was definite ST within the first year. A competitive risk analysis was carried out using a Fine and Gray regression model, with death being the competitive event. Results: A total of 2604 patients received DAPT with ticagrelor and 1519 with prasugrel; ST occurred in 41 patients (1.10%), with a similar cumulative incidence between ticagrelor (1.21%) and prasugrel (0.90%). The independent predictors of ST were age (sHR, 1.03; 95%CI, 1.01-1.06), ST segment elevation (sHR, 2.24; 95%CI, 1.22-4.14), previous myocardial infarction (sHR, 2.56; 95%CI, 1.19-5.49), and serum creatinine (sHR, 1.29; 95%CI, 1.08-1.54). Conclusions: Stent thrombosis is infrequent in patients receiving DAPT with ticagrelor or prasugrel. The variables associated with an increased risk of ST were advanced age, ST segment elevation, previous myocardial infarction, and serum creatinine

Renin-Angiotensin System Blockade and Risk of Heart Failure After Myocardial Infarction Based on Left Ventricular Ejection Fraction: A Retrospective Cohort Study.

INTRODUCTION: The goal of this study was to determine the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) and follow-up heart failure (HF) according to left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI). METHODS: This cohort study used a retrospective registry of 8169 consecutive patients discharged with a diagnosis of AMI from two university hospitals in Spain between 2010 and 2016. We used a multivariable competing risk analysis, survival-time inverse probability weighting (IPW) propensity score adjusting, and propensity score matching (PSM) to investigate the association between ACEI/ARB treatment and follow-up HF. RESULTS: During the follow-up (3.3 ± 2.2 years), 1296 patients were admitted for HF (5.2 per 100 person-years). ACEI/ARB use was not associated with fewer follow-up HF admissions in patients with LVEF > 40% (univariate analysis: sub-hazard ratio [sHR] 1.10; 95% confidence interval [CI] 0.95-1.27; p = 0.197; IPW adjusting analysis: sHR 1.11; 95% CI 0.95-1.29; p = 0.192; PSM analysis: sHR 1.12; 95% CI 0.92-1.36; p = 0.248). However, ACEI/ARB use was associated with a significant reduction in HF admission rates in patients with LVEF ≤ 40% (univariate analysis: HR 0.70; 95% CI 0.56-0.88; p = 0.003; IPW adjusting analysis: HR 0.64; 95% CI 0.50-0.83; p = 0.001; PSM analysis: HR 0.65; 95% CI 0.46-0.92; p = 0.014). CONCLUSION: Among hospitalized survivors of AMI, the use of ACEIs/ARBs was associated with a lower risk of follow-up HF in patients with LVEF ≤ 40% but not in those with LVEF > 40%. Further prospective studies are needed to confirm our results.

Utilidad de la puntuación PARIS para evaluar el equilibrio isquémico-hemorrágico con ticagrelor y prasugrel tras un síndrome coronario agudo / Usefulness of the PARIS score to evaluate the ischemic-hemorrhagic net benefit with ticagrelor and prasugrel after an acute coronary syndrome

Introducción y objetivos: La puntuación PARIS permite una estratificación combinada de los riesgos isquémico y hemorrágico de los pacientes con cardiopatía isquémica tratados con stent coronario y tratamiento antiagregante plaquetario doble (TAPD). Se desconoce su utilidad en pacientes con síndrome coronario agudo (SCA) tratados con ticagrelor o prasugrel. Se investiga este aspecto en un registro internacional. Métodos: Estudio retrospectivo multicéntrico con participación voluntaria de 11 centros de 6 países europeos. Se estudio ́a 4.310 pacientes con SCA dados de alta en TAPD con ticagrelor o prasugrel. Se definío evento isquémico como trombosis de stent o infarto de miocardio espontáneo, y evento hemorrágico según BARC (Bleeding Academic Research Consortium) tipo3 o 5. Se calculó la discriminación y la calibración para ambas vertientes de la puntuación PARIS (PARISisquémico y PARIShemorrágico). El beneficio neto isquémico-hemorrágico se obtuvo mediante la diferencia entre las probabilidades predichas de eventos isqueémicos y hemorrágicos. Resultados: Durante 17,2 ± 8,3 meses, hubo 80 eventos isquémicos (el 1,9% anual) y 66 eventos hemorrágicos (el 1,6% anual). PARISisquémico y PARIShemorrágico se asociaron con el riesgo de evetos isquémicos (sHR=1,27; IC95%, 1,16-1,39) y hemorrágicos (sHR = 1,14; IC95%, 1,01-1,30) respectivamente. La discriminación de eventos isquémicos fue discreta (índice C = 0,64) y la de eventos hemorrágicos, pobre (índice C= 0,56), con buena calibración para ambos. El beneficio neto isquémico-hemorrágico resultó negativo (más eventos hemorrágicos) en pacientes con alto riesgo hemorrágico y positivo (más eventos isquémicos) en pacientes con alto riesgo isquémico. Conclusiones: En pacientes con SCA tratados con TAPD conticagrelor o prasugrel, la escala PARIS ayuda a establecer un equilibrio apropiado del riesgo isquémico-hemorrágico

Introduction and objectives: The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy(DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry. Methods: Retrospective multicenter study with voluntary participation of 11 centers in 6 European countries. We studied 4310 patients with ACS discharged with DAPT with ticagrelor or prasugrel. Ischemic events were defined as stent thrombosis or spontaneous myocardial infarction, and hemorrhagic events as BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding. Discrimination and calibration were calculated for both PARIS scores (PARISischemic and PARIShemorrhagic). The ischemic-hemorrhagic net benefit was obtained by the difference between the predicted probabilities of ischemic and bleeding events. Results: During a period of 17.2 ± 8.3 months, there were 80 ischemic events(1.9% per year) and 66 bleeding events (1.6% per year). PARISischemic and PARIShemorrhagic scores were associated with a risk of ischemic events (sHR, 1.27; 95%CI, 1.16-1.39) and bleeding events (sHR, 1.14; 95%CI, 1.01-1.30), respectively. The discrimination for ischemic events was modest (Cindex = 0.64) and was suboptimal for hemorrhagic events (Cindex = 0.56), where as calibration was acceptable for both. The ischemic-hemorrhagic net benefit was negative (more hemorrhagic events) in patients at high hemorrhagic risk, and was positive (more ischemicevents) in patients at high ischemic risk. Conclusions: In patients with ACS treated with DAPT with ticagrelor or prasugrel, the PARIS model helps to properly evaluate the ischemic-hemorrhagic risk

Risk of cancer after an acute coronary syndrome according to the type of P2Y12 inhibitor.

INTRODUCTION: There are conflicting clinical and laboratory data about the effect of dual antiplatelet therapy (DAPT) on cancer incidence, including analysis suggesting an increased cancer risk. This study aims to analyze if there are differences in the incidence of cancer according to the type of P2Y12 inhibitor prescribed (clopidogrel, prasugrel, or ticagrelor), among a population of acute coronary syndrome (ACS) survivors treated with DAPT. MATERIAL AND METHODS: A retrospective study was conducted among 4229 consecutive ACS patients discharged from a tertiary hospital with DAPT from 2010 to 2016. Cox regression, propensity score, and survival-time inverse probability analysis were done. RESULTS: A total of 311 were diagnosed of cancer during a median follow-up of 46.2 months. The cumulative incidence function (CIF) of cancer (per 100 patients/year) was 2.2 for clopidogrel, 1.6 for prasugrel, and 0.3 for ticagrelor. After multivariate analysis, we have found that ticagrelor resulted associated with lower cancer risk than clopidogrel (sHR 0.20: 95% CI 0.05-0.84; p = 0.028), without differences between prasugrel and clopidogrel. After propensity score matching, ticagrelor was also associated with lower incidence of cancer than clopidogrel/prasugrel (sHR 0.22; 95% CI 0.05-0.90; p = 0.036), regardless of DAPT duration. CONCLUSION: DAPT with ticagrelor could be associated with lower follow-up cancer incidence than DAPT with clopidogrel or prasugrel after an ACS.

Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome.

INTRODUCTION AND OBJECTIVES: The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry. METHODS: Retrospective multicenter study with voluntary participation of 11 centers in 6 European countries. We studied 4310 patients with ACS discharged with DAPT with ticagrelor or prasugrel. Ischemic events were defined as stent thrombosis or spontaneous myocardial infarction, and hemorrhagic events as BARC (Bleeding Academic Research Consortium) type 3 or 5 bleeding. Discrimination and calibration were calculated for both PARIS scores (PARISischemic and PARIShemorrhagic). The ischemic-hemorrhagic net benefit was obtained by the difference between the predicted probabilities of ischemic and bleeding events. RESULTS: During a period of 17.2 ± 8.3 months, there were 80 ischemic events (1.9% per year) and 66 bleeding events (1.6% per year). PARISischemic and PARIShemorrhagic scores were associated with a risk of ischemic events (sHR, 1.27; 95%CI, 1.16-1.39) and bleeding events (sHR, 1.14; 95%CI, 1.01-1.30), respectively. The discrimination for ischemic events was modest (C index = 0.64) and was suboptimal for hemorrhagic events (C index = 0.56), whereas calibration was acceptable for both. The ischemic-hemorrhagic net benefit was negative (more hemorrhagic events) in patients at high hemorrhagic risk, and was positive (more ischemic events) in patients at high ischemic risk. CONCLUSIONS: In patients with ACS treated with DAPT with ticagrelor or prasugrel, the PARIS model helps to properly evaluate the ischemic-hemorrhagic risk.