Fibrilación auricular una arritmia y un sindrome / Atrial fibrillation, an arrhythmia and a syndrome

Atrial Fibrillation (AF) is the most common sustained arrhythmia and is highly prevalent in elderly patients. It confers a higher risk for ischemic stroke, heart failure and death. The diagnosis and treatment of AF has been extensively studied and remain under constant revision. This article reviews the recent European guidelines and the advances observed with the introduction of direct oral anticoagulants in the last ten years. This new family of drugs has clear benefits in terms of efficacy and safety compared with traditional vitamin K antagonists. Treatment of most common comorbidities in patients with AF such as advanced age, heart failure, diabetes, renal failure, and others are also analyzed. New therapies for AF will be shortly available.

Bernard Lown y el arte de sanar / Bernard Lown and the art of healing

RESUMEN: Se presenta una semblanza del Dr. Bernard Lown, uno de los más destacados cardiólogos del siglo XX. Muy relevantes fueron sus estudios sobre arritmias ventriculares e isquemia miocárdica, como también la influencia del estrés sobre el umbral de la fibrilación ventricular. Simultáneamente con otros investigadores europeos desarrolló el cardiovertor eléctrico. Se releva particularmente su condición de gran clínico y el trato humano con sus pacientes. Finalmente, se destaca su contribución a evitar una guerra nuclear por lo cual, junto al Dr Chazov, recibió el Premio Nobel de la Paz.

ABSTRACT: This is a biographical note on Bernard Lown MD, recently deceased. He was one of the foremost cardiologist in the XXth century. Relevant were his studies on ventricular arrhythmias and myocardial ischemia, as well the effect of mental stress in lowering the ventricular arrhythmia threshold. Along with European researchs he developed the electric cardiovertor. Special emphasis is placed on his skills as a clinician and is humane approach to patient care. He contributed to international efforts to prevent nuclear war. For this effort he was awarded, along with Dr Chazov, the Nobel Peace Price.

VCAM-1 as a predictor biomarker in cardiovascular disease.

The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during inflammation. VCAM-1 expression, together with soluble VCAM-1 (sVCAM-1) induced by the shedding of VCAM-1 by metalloproteinases, have been proposed as biomarkers in immunological diseases, cancer, autoimmune myocarditis, and as predictors of mortality and morbidity in patients with chronic heart failure (HF), endothelial injury in patients with coronary artery disease, and arrhythmias. This revision aims to discuss the role of sVCAM-1 as a biomarker to predict the occurrence, development, and preservation of cardiovascular disease.

Preoperative soluble VCAM-1 contributes to predict late mortality after coronary artery surgery.

BACKGROUND: Soluble vascular cell adhesion molecule-1 has been associated with long-term cardiovascular mortality in patients with stable coronary artery disease and to the development of new atrial fibrillation in subjects with cardiovascular risk factors but no evidence of cardiac disease. HYPOTHESIS: Preoperative soluble vascular cell adhesion molecule-1 predicts the risk of future all-cause death and cardiovascular death among patients submitted to elective coronary artery bypass surgery. METHODS: From a cohort of 312 patients who underwent elective coronary artery bypass surgery prospectively followed for a median of 6.7 years, we evaluated the prognostic role of preoperative soluble vascular cell adhesion molecule-1, inflammatory markers, CHA2DS2-VASc score and development of postoperative atrial fibrillation (POAF). Univariable and multivariable Cox regression analyses were performed to establish an association of these parameters with long term all-cause death and cardiovascular death. RESULTS: During 2112 person-years of follow-up, we observed 41 deaths, 10 were cardiovascular deaths. Independently increased levels of preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score were associated with all-cause mortality. After multivariate adjustment, elevated preoperative soluble vascular cell adhesion molecule-1 and POAF were the only independent predictors of all-cause death. Also, preoperative soluble vascular cell adhesion molecule-1, POAF, and CHA2DS2-VASc score resulted in being independent predictors of cardiovascular mortality. CONCLUSIONS: Increased circulating levels of preoperative soluble vascular cell adhesion molecule-1, together with POAF and CHA2DS2-VASc score, were significantly associated with future all-cause death and cardiovascular death among patients submitted to coronary artery bypass surgery.

Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.

AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF.

Long-term ticagrelor for secondary prevention in patients with prior myocardial infarction and no history of coronary stenting: insights from PEGASUS-TIMI 54.

AIMS: PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. METHODS AND RESULTS: This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1-3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15-1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68-0.99) and with prior stenting (HR 0.85, 95% CI 0.75-0.96; P for interaction = 0.76). CONCLUSION: Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. CLINICALTRIALS.GOV IDENTIFIER: NCT01225562.

Reperfusión fármaco-invasiva en el manejo del infarto agudo de miocardio en Chile: un llamado a la acción / Pharmaco-invasive reperfusion in acute myocardial infarction in Chile: a call for action

Resumen En Chile, se han logrado avances importantes en el manejo del Infarto Agudo de Miocardio (IAM) con elevación del segmento ST (IAMCEST). Debido a la mejoría en el diagnóstico precoz y tratamiento, particularmente, con el incremento de la Angioplastía Primaria (APP), hoy están dadas las condiciones para seguir progresando por la vía de la combinación de estrategias de reperfusión y la creación de Redes de Manejo del IAM. El siguiente artículo revisa la evidencia que justifica impulsar dicho avance y se esbozan posibles caminos para lograrlo.

Abstract In Chile, important advances have been made in the management of Acute Myocardial Infarction (MI) with ST segment elevation (STEMI). Due to the progress in early diagnosis and treatment, particularly with the increase in Primary Angioplasty (Primary PCI), nowadays there are conditions to improve early management through the combination of reperfusion strategies and the implementation of MI reperfusion networks. The present article reviews the evidence justifying the promotion of this strategy and outlines possible actions to achieve it.

Manejo de hemorragia asociada a anticoagulantes orales directos: estado actual de las estrategias de reversión / Management of bleeding associated with direct oral anticoagulants: update on reversal strategies

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.

Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD-AF registry: Rationale for comprehensive management of atrial fibrillation.

BACKGROUND: The factors influencing three major outcomes-death, stroke/systemic embolism (SE), and major bleeding-have not been investigated in a large international cohort of unselected patients with newly diagnosed atrial fibrillation (AF). METHODS AND RESULTS: In 28,628 patients prospectively enrolled in the GARFIELD-AF registry with 2-year follow-up, we aimed at analysing: (1) the variables influencing outcomes; (2) the extent of implementation of guideline-recommended therapies in comorbidities that strongly affect outcomes. Median (IQR) age was 71.0 (63.0 to 78.0) years, 44.4% of patients were female, median (IQR) CHA2DS2-VASc score was 3.0 (2.0 to 4.0); 63.3% of patients were on anticoagulants (ACs) with or without antiplatelet (AP) therapy, 24.5% AP monotherapy, and 12.2% no antithrombotic therapy. At 2 years, rates (95% CI) of death, stroke/SE, and major bleeding were 3.84 (3.68; 4.02), 1.27 (1.18; 1.38), and 0.71 (0.64; 0.79) per 100 person-years. Age, history of stroke/SE, vascular disease (VascD), and chronic kidney disease (CKD) were associated with the risks of all three outcomes. Congestive heart failure (CHF) was associated with the risks of death and stroke/SE. Smoking, non-paroxysmal forms of AF, and history of bleeding were associated with the risk of death, female sex and heavy drinking with the risk of stroke/SE. Asian race was associated with lower risks of death and major bleeding versus other races. AC treatment was associated with 30% and 28% lower risks of death and stroke/SE, respectively, compared with no AC treatment. Rates of prescription of guideline-recommended drugs were suboptimal in patients with CHF, VascD, or CKD. CONCLUSIONS: Our data show that several variables are associated with the risk of one or more outcomes, in terms of death, stroke/SE, and major bleeding. Comprehensive management of AF should encompass, besides anticoagulation, improved implementation of guideline-recommended therapies for comorbidities strongly associated with outcomes, namely CHF, VascD, and CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01090362.

Características basales, manejo de terapias antitrombóticas y pronóstico de pacientes chilenos con FA no valvular. Lecciones del Registro GARFIELD AF en Chile / Features, management and prognosis of Chilean patients with non valvular atrial fibrillation: GARFIELD AF registry

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF. Aim: To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry. Material and Methods: Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up. Results: The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up. Conclusions: Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.

Increased C-reactive protein plasma levels are not involved in the onset of post-operative atrial fibrillation.

BACKGROUND: Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been associated with the initiation and perpetuation of atrial fibrillation (AF). However, it is not known whether an increased CRP plasma level, without concomitant inflammation, is sufficient to induce AF. We investigated whether higher CRP plasma levels, determined by the presence of +219G>A CRP gene polymorphism, is associated with an increased risk of post-operative AF. METHODS: One hundred and fifteen adult patients submitted to elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: CRP plasma levels before surgery were higher in GG than in GA+AA patients (3.4±3.1 vs. 1.7±1.8, p<0.015). Thirteen percent of the patients presented post-operative AF. Despite the positive correlation between the polymorphism and CRP levels, there was no significant difference in the occurrence of post-operative AF between the different genotypes. CONCLUSIONS: These results suggest that increased CRP plasma levels that are not associated with an inflammatory process are not sufficient to trigger AF after cardiac surgery.

Novel Therapies Targeting Cardioprotection and Regeneration.

Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such as myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such as cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy. Moreover, cardiomyocytes are unable to regenerate; thus, lost cells are replaced with fibrotic tissue, with a potentially severe impact on myocardial function. Several therapeutic agents and strategies to reduce cardiomyocyte damage are currently available. This manuscript reviews the state of the art regarding novel cardioprotective endogenous peptides, such as neuregulin-1, angiotensin-(1-9), growth/differentiation factor-11, growth/differentiation factor- 15 and insulin-like growth factor-1. We discuss their protective effects and therapeutic potential in cardiovascular diseases and the current challenges to harnessing their full cardioprotective power. We also explore targeting of exosomes as a cardioprotective approach along with the therapeutic potential of cardiac regeneration strategies. Further advances associated with these molecules and cardioprotective approaches may provide more effective therapies to attenuate or prevent cardiomyocyte death, thereby preserving the myocardium.

Strain auricular izquierdo y biomarcadores cardíacos como predictores de accidente cerebrovascular en pacientes con fibrilación auricular de reciente comienzo / Left atrial strain and biomarkers for stroke in patients with recent onset atrial fibrillation

Introducción: La miopatía y fibrosis auricular representan el sustrato protrombótico y proarrítmico en pacientes con fibrilación auricular (FA). Estudios recientes muestran relación entre el strain auricular izquierdo (SAI), eventos cardiovasculares y recurrencia en pacientes con FA. La asociación entre SAI y bio-marcadores cardíacos como predictores de accidente cerebrovascular silente (ACVs) en pacientes con FA de reciente comienzo (FArc) no ha sido estudiada. Objetivo: Determinar si la asociación entre SAI y biomarcadores cardíacos contribuye a la predicción de ACV en pacientes con FArc. Métodos: Se realizó un estudio prospectivo que permitió reclutar 57 pacientes con FArc (primer episodio de < de 8 semanas de evolución). Obtenido consentimiento informado (CI) se realizó recolección de datos clínicos y muestras de sangre para determinación de Pro-BNP, Dimero-D y GDF-15. Se realizó resonancia nuclear magnética cerebral (RNMc) y ecocardiograma transtorácico (ETT) durante los primeros 3 días de inclusión y en ritmo sinusal. Para la evaluación de SAI se consideró la curva de deflexión positiva durante la sístole ventricular (SAIs), derivada de speckle tracking, considerando el promedio de 5 ciclos. Se utilizó Mann Whitney U test y Spearman Rho para análisis estadístico. Resultados: La edad promedio fue 70±8,2 años y el 70% fueron hombres. El CHA2DS2-VASc score promedio fue 3,1±1 y el promedio de pro-BNP, Di-mero-D y GDF-15 fue 96,1±12,4 pg/ml, 990±140 ng/ ml y 12 ng/ml respectivamente. 15% de los pacientes (n=9) presentaban ACVs en la RNMc al momento del diagnóstico. Se observó, además, que los pacientes con ACV presentaban un SAIs más bajo que los pacientes sin eventos (5,5±1,1% y 14,6±7,3% respectivamente p=0.04). Adicionalmente, se encontró una correlación significativa entre SAIs y pro-BNP, Dimero-D y GDF-15. Conclusiones: En este trabajo se evidenció que el 15% de los pacientes con FArc presenta ACVs al momento del diagnóstico. El SAIs bajo se correlaciona de forma inversa con los biomarcadores de sobrecarga, trombogénesis, fibrosis auricular y presencia de ACV silente. Estos resultados pueden ser utilizados para una mejor estratificación del riesgo de ACV en pacientes con FA.

Introduction: Atrial myopathy and fibrosis constitute a pro-arrhythmic and pro-thromboembolic substrate in patients with atrial fibrillation (AF). Recent studies using left atrial strain (LAS) have shown that LAS contributes to predict AF recurrence in patients with paroxysmal AF. The association between LAS and cardiac biomarkers in predicting silent stroke (SS) in patients with new AF has not been studied. Aim: The association of LAS and cardiac biomarkers contribute to predict SS in patients with new AF. Methods: We have prospectively evaluated 57 consecutive patients with new AF (first episode with less than 8 weeks of evolution). Baseline clinical characteristics and blood samples for determinations of Pro-BNP, D-Dimer and GDF-15 were obtained. Brain magnetic resonance (BMRI) and 2D Echo were performed within 3 days. In sinus rhythm, the positive deflection during ventricular systole of the LAS curve derived from speckle tracking was considered (mean of 5 cycles) (LASS). Mann Whitney U test and Spearman Rho were used for statistical analysis. Results: Mean age was 70±8,2 years, 70% were men. The mean CHA2DS2-VASc score was 3,1±1. Mean pro-BNP, D-Dimer and GDF-15 were 96,1±12,4 pg/ml, 990±140 ng/ml and 12 ng/ml, respectively. Fifteen percent of patients (n=9) had evidence of previous SS in BMRI. Patients with SS had significantly less LASS than patients without events (5,5±1,1% and 14,6±7,3% respectively p=0,04). In addition, a significant correlation between LASs and pro-BNP, D-Dimer and GDF-15 was found. Conclusion: Evidence of SS was found in 15% of patients with new AF. This was associated with LASs impairment, which was inversely correlated with cardiac biomarkers of LV overload, thrombogenesis and LA fibrosis. These findings could be utilized for a better risk stratification of stroke in patients with new AF.

Impacto de un programa de rehabilitación cardiovascular fase II sobre la calidad de vida de los pacientes / Quality of life: impact of a phase II cardiovascular rehabilitation program

Antecedentes: La rehabilitación cardiovascular (RCV) ha demostrado mejorar la capacidad física (CF) y la calidad de vida. La relación de estos aspectos ha sido escasamente reportada en Chile. Objetivos: 1) Determinar el impacto de la RCV fase II sobre la calidad de vida, medida por la encuesta SF36 y, 2) determinar qué factores, relacionados con el paciente, pueden incidir en esta relación. Método: Estudio prospectivo en sujetos que completaron 36 sesiones de un programa de RCV y Prevención Secundaria (PREV2). Se registraron al ingreso y final de la RCV: antecedentes médicos, factores de riesgo cardiovascular (CV), parámetros antropométricos, previsión de salud, CF (determinada por los metros caminados en test de marcha de 6 minutos-TM6) y puntaje en la encuesta SF36. Resultados: 277 sujetos (78% hombres, edad 59 años). Hubo una mejoría significativa en: a) los metros caminados (diferencia final/inicial= 56 metros, p<0.0001), b) puntaje de salud física (68 vs 79; p<0.0001), c) salud emocional (68 vs 78, p<0.0001) del SF36. Los hombres caminaron más metros promedio (p<0.0001). Hubo una asociación significativa entre los deltas del TM6 final-inicial y SF36 final-inicial, sólo para salud física (p<0.01). Por un aumento de 10 metros caminados en el TM6 final se incrementa el puntaje de la SF36 para salud física (Hombres: 0.38/ Mujeres: 1.52). La mejoría en la salud emocional sólo se asoció significativamente con los cambios en la salud física (p<0.0001). Conclusion: Los pacientes que asisten a un programa de RCV mejoran significativamente su capacidad aeróbica, y su percepción de salud física y emocional.

Background: Cardiovascular rehabilitation (CVR) has been shown to improve functional capacity (FC) and quality of life. The relation between these aspects has been scarcely reported in Chile. Objectives: 1) To determine the impact of the CVR phase II program on quality of life as measured by the SF36 survey and 2) to determine which patient related factors can influence this relationship. Method: Prospective study in subjects who completed 36 sessions of an RCV and Secondary Prevention program (PREV2). Medical records, cardiovascular risk factors (CV), anthropometric parameters, health forecast, functional capacity (FC) (determined by meters walked on 6-minute Walking test-TM6) and SF36 scores were recorded at the beginning and end of the CVR. Results: Data on 277 subjects (78% men, age 59 years) was analyzed. There was a significant improvement in: a) walking meters (final / initial difference = 56 meters, p <0.0001), b) physical health score (68 vs 79, p <0.0001), c) emotional health (68 vs 78, p <0.0001) of the SF36. The men walked more meters (p <0.0001). There was a significant association between delta TM6 final-initial and SF36 final-initial only for physical health (p <0.01). For an increase of 10 meters walked in the final TM6, SF36 score for physical health increased 0.38 points in men ad 1.52 in women. Improvement in emotional health was significantly associated only with changes in physical health (p <0.0001). Conclusion: Patients attending a phase II cardiovascular rehabilitation program significantly improve their aerobic capacity, and their perception of physical and emotional health.

Implante percutáneo de válvula aórtica con apoyo de circulación extracorpórea en paciente con insuficiencia aórtica severa / Trans catheter aortic valve implantation with extra corporeal circulation support in a patient with severe aortic insufficiency

An 84-year man with prior coronary artery bypass surgery and endovascular repair of an abdominal aortic aneurysm developed congestive heart failu-re. He had calcific aortic valve disease with severe regurgitation. A #29 Edwards-Sapien aortic valve via trans-apical approach was implanted with the patient connected to extra corporeal circulation. The patient recovered successfully and remained in functional class II 8 months after hospital dis-charge.

Evaluación de la anticoagulación con rivaroxaban, en pacientes con fibrilación auricular no valvular de reciente diagnóstico / Evaluation of oral anticoagulation with rivaroxaban, in patients with new onset non valvular atrial fibrillation

Background: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. Aim: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. Patients and Methods: Prospective study in patients with indication of anticoagulation. Demographic variables, cardiovascular risk factors, CHA2DS2-VASc and HAS-BLED scores were recorded. Blood samples were taken at baseline, at 3 and 24 hours after the administration of the drug and at 30 days. Rivaroxaban levels, anti-Xa activity, prothrombin time, thrombin generation and plasma levels of thrombin-antithrombin complexes were determined. Results: We studied 20 patients aged 76.3 ± 8.0 years (60% female) with a CHA2DS2-VASc score > 2 points. The anti-Xa factor activity correlated with rivaroxaban plasma levels at 3 hours (r = 0.61, p < 0.01), at 24 hours (r = 0.85, p < 0.01) and at 30 days (r = 0.99, p < 0.01), with prothrombin time at 3 hours (r = -0.86, p = 0.019) and at 30 days (r = -0.63, p = 0.02) and with a sustained decrease in thrombin generation at 30 days of follow-up (r = -0.74, p < 0.01). There was no correlation with thrombin-antithrombin complexes (r = -0.02, p = 0.83). Conclusions: Rivaroxaban consistently inhibited the mild pro-coagulant state found in newly diagnosed non-valvular AF patients through the first 24 hours and this effect was maintained at 30 days. Plasma levels of the drug correlated with anti-Xa factor activity, thrombin generation and prothrombin time

Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction.

BACKGROUND: Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar. METHODS: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding. RESULTS: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients. CONCLUSIONS: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474.

Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease.

BACKGROUND: Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI). OBJECTIVES: This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI. METHODS: PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up. RESULTS: A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026). CONCLUSIONS: Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).

[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. / Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio.

BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.