Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Mean Platelet Volume as Prognostic Marker in Patients with Acute Coronary Syndrome

  Background: Mean platelet volume (MPV) has been described as a predictor of cardiovascular events in patients with acute coronary syndrome. However, there is limited evidence of its role as prognostic marker in elderly patients. Objective: The aim of this study was to evaluate whether MPV is an independent predictor of events during follow-up of patients over 65 years of age with acute coronary syndrome. Methods: This prospective study included patients over 65 years with ST-segment elevation or non ST-segment elevation acute coronary syndrome. They were divided into two groups: high MPV (10.9 fL- 3rd tertile) and low MPV (<10.9 fL -1st and 2nd tertile). Different clinical variables were analyzed and the TIMI and GRACE scores were calculated. The primary endpoint was the composite of all-cause mortality and cardiovascular readmission (for acute coronary syndrome, heart failure and stroke) over the follow-up period. Results: A total of 250 patients were included in the study. Mean age was 74±7 years and 44% were women. Eighty-five patients presented with high and 165 with low MPV. Median follow-up was 302 days (interquartile range 130-558) and the primary endpoint was observed in 17.6% of cases (44 patients). In the multivariate Cox regression analysis, high MPV [HR 7.23 (95% CI 2.47-11.6); p=0.001], and TIMI [HR 3.10 (95% CI 1.46-6.59); p=0.03] and GRACE [HR 1.02 (95% CI 1.01-1.07); p=0.002] high risk scores were independent predictors of the primary endpoint. The area under the curve for MPV was 0.71 (95% CI 0.59-0.82), p=0.001. Conclusions: In our population, MPV emerged as an independent predictor of the composite endpoint, adjusted for other variables as the TIMI and GRACE scores.INTRODUCCIÓN Se ha descripto al volumen plaquetario medio (VPM)  como predictor de eventos cardiovasculares en pacientes con SCA. Hay poca evidencia en pacientes añosos. El objetivo de este trabajo es evaluar si el VPM es un predictor independiente de eventos en el seguimiento en pacientes mayores de 65 años con SCA. MATERIALES Y METODOS Estudio prospectivo que incluyó pacientes mayores de 65 años con SCA con y sin elevación del ST. Se dividieron en dos grupos: VPM alto (≥ 10,9 fL- tercilo 3) y VPM bajo (<10,9 fL -tercilos 1 y 2). Se analizaron diferentes variables clínicas y se calcularon los scores TIMI y GRACE. Se consideró el punto final combinado de mortalidad global y reinternación cardiovascular (por SCA, Insuficiencia cardíaca y Stroke) en el seguimiento. RESULTADOS. Se incluyeron 250 pacientes con una edad de 74 ± 7 años, 44% mujeres. En el grupo VPM alto hubo 85 pacientes y 165 en el VPM bajo  La mediana de seguimiento fue 302 días (rango intercuartilo 130-558) y el punto primario se observó en el 17,3% (44 pacientes). En el análisis multivariado por regresión Cox el VPM alto fue predictor independiente del punto primario (HR 7,23 (IC95% 2,47-11,6), p=0,001), al igual que el TIMI alto riesgo (3,10 (IC95% 1,46-6,59), p=0,03) y el Score GRACE (1,02 (IC95% 1,01-1,07), p=0,002). El VPM presentó un ABC 0,71 (IC95%  0,59-0,82), p=0,001. CONCLUSIONES. En nuestra población el VPM se comportó como predictor independiente del punto combinado, ajustado a otras variables como el score TIMI y GRACE

Association between Mean Platelet Volume and Resistance to Aspirin and P2Y12 Receptor Inhibitors in Elderly Patients with Acute Coronary Syndrome

Background: Antiplatelet resistance and mean platelet volume (MPV) are event predictors in acute coronary syndrome (ACS), buttheir association has been poorly studied.Objective: The aim of this study was to evaluate the association between MPV and resistance to aspirin (ASA) and P2Y12 receptorinhibitors (P2Y12i) in elderly patients with ACS.Methods: Patients over 65 years old diagnosed with ACS were included in the study. They were divided into group 1 (resistance toboth antiplatelet agents), group 2 (resistance to one antiplatelet agent) and group 3 (no resistance to antiplatelet agents). Plateletaggregation was measured between 12 and 24 hours postloading (by light transmission aggregometry). Resistance to P2Y12i wasconsidered as maximum percentage of aggregation (MPA) with adenosine diphosphate (ADP) >60% and resistance to ASA as MPAwith arachidonic acid (ARA) >20%. The composite endpoint of global death and cardiovascular re-hospitalization was consideredduring follow-up.Results: One hundred and ninety five patients included in the study received ASA and P2Y12i (120 received clopidogrel and 75ticagrelor). Nineteen percent of patients belonged to group 1, 34.4% to group 2 and 46.6% to group 3. Mean platelet volume wasassociated with resistance to both antiplatelet agents [OR 1.02 (95% CI 1.01-1.05), p=0.03], while MPV and the GRACE score wereindependent predictors of the composite endpoint [HR 1.03 (95% CI 1.01-1.07), p=0.04, and HR 1.02 (95% CI 1.01-1.04), p=0.02,respectively].Conclusions: Mean platelet volume was associated with the presence of resistance to both antiplatelet agents. During follow-up,MPV and the GRACE score were predictors of the composite endpoint.Introducción La presencia de resistencia a antiagregantes y el volumen plaquetario medio (VPM) son predictores de eventos en el síndrome coronario agudo (SCA). La asociación entre ambos ha sido poco estudiada. Objetivo Evaluar si existe asociación entre la presencia de resistencia a la aspirina (AAS) e inhibidores del receptor P2Y12 (iP2Y12) y el VPM en pacientes mayores de 65 años con SCA. Materiales y Métodos Se incluyeron pacientes mayores de 65 años con diagnóstico de SCA. Se dividieron en: grupo 1 (resistencia a ambos antiagregantes), grupo 2 (a uno de los antiagregantes) y grupo 3 (a ningún antiagregante). Se midió agregación plaquetaria entre las 12 y 24 horas postcarga (por light transmission aggregometry ). Se consideró resistencia a iP2Y12 a un porcentaje máximo de agregación (PMA) con ADP > 60% y a la AAS a un PMA con ARA > 20%.  En el seguimiento se consideró el punto final combinado de muerte global y reinternación cardiovascular. Resultados Se incluyeron 195 pacientes, todos recibieron AAS e iP2y12 (120 recibieron clopidogrel y 75 Ticagrelor). Grupo 1 (19%), Grupo 2 (34.4%) y grupo 3 (46.7%). El VPM  se asoció a la resistencia a ambos antiagregantes (OR 1.02 (IC95% 1.01-1.05), p=0.03. A su vez, el VPM y el GRACE fueron predictores independientes del punto combinado (HR 1.03 (IC95% 1.01-1.07), p=0.04 y HR 1.02 (IC95% 1.01-1.04), p=0.02), respectivamente. Conclusiones El VPM se asoció a la presencia de resistencia a ambos antiagregantes. En el seguimiento, el VPM y el score GRACE fueron predictores del punto combinado

Presencia de trombo y contraste espontáneo en aurícula izquierda en pacientes con fibrilación auricular, anticoagulados con dabigatrán y acenocumarol

Introducción: El Dabigatran (DAB) ha demostrado una eficacia similar a la warfarina en la prevención embolias en pacientes con fibrilación auricular, pero debe administrarse con precaución en pacientes ancianos. El trombo en aurícula izquierda (TAI) es un importante marcador de embolias. Objetivos: Evaluar la presencia de TAI en pacientes ≥  65 años, con FA persistente en plan de CVE que reciben tratamiento con DAB o acenocumarol (AC). Materiales y Métodos. Se incluyeron en forma prospectiva pacientes  ≥ 65 años con FA persistente en plan de CVE que se encontraban en tratamiento con DAB (dosis 110 mg o 150 mg dos veces día en  ≥ o < de 75 años, respectivamente) o AC. Se les realizó ecocardiograma transesofágico (ETE) previa a la CVE buscando la presencia TAI y contraste espontaneo en AI (CEspAI). Puntos secundarios: Tromboembolias cerebral o sistémica  y el sangrado mayor al mes. Resultados Se incluyeron 101 pacientes, 45 recibían DAB (23 con dosis 110 mg  y 22 con dosis 150 mg) y 56 AC.  Se encontró TAI en el 8,9% versus 19,6% (RR de 0,45 (IC 95% 0,15 – 1,32),p=0,08) y CEspAI en el 20%  versus  44,5% (RR 0,44 (IC95% 0,23 – 0,86), p=0,007) en los grupos DAB y AC, respectivamente  Al mes  se registraron 2 embolias, ambas en el grupo AC (p=0,3) y 4 pacientes con sangrado mayor, dos en cada grupo (p=0,5). Conclusión El DAB presento menor CEspAI y una tendencia a menor TAI que los pacientes con AC. No hubo diferencias  en la tasa de embolias, ni de sangrado mayor al mes de seguimiento

Usefulness of Different Mortality Risk Scores in Patients with Heart Failure. A Retrospective and Observational Study

Background: The Cardiac and Comorbid Conditions - Heart Failure (3C-HF) and the Meta-Analysis Global Group in ChronicHeart Failure (MAGGIC) are two score models developed to predict mortality in patients with heart failure (HF). The performanceof these scores has been little studied in our setting.Objective: The aim of this study was to assess the performance of the 3C-HF and the MAGGIC scores to predict one-yearmortality in a population of patients with HF.Methods: Ambulatory HF patients discharged after hospitalization due to acute HF in two centers were included in the study.The 3C-HF and MAGGIC scores were calculated and one-year mortality was the study endpoint. The discrimination abilityof the scores was analyzed from the calculated area under the ROC curve and their calibration quality was assessed applyingthe Hosmer-Lemeshow test. Both areas under the ROC curve were compared using the Hanley-Mc Neil test.Results: A total of 704 patients with mean age of 73±11 years and 39.6% women were included in the study. One-year mortalitywas 12.4% (n=87). Both scores were independent predictors of mortality, with HR of 1.03 (95% CI 1.008-1.06; p=0.02)and 1.08 (95% CI 1.02-1.13; p=0.004) for the 3C-HF and MAGGIC scores, respectively. The area under the ROC curve for the3C-HF score was 0.70 (95% CI 0.64-0.75) and for the MAGGIC score 0.67 (95% CI 0.61-0.73), without significant differencesbetween them (p=0.41). Both scores presented adequate calibration (p=0.06 and p=0.32, respectively).Conclusion: The 3C-HF and MAGGIC scores were predictors of one-year mortality, with a moderate ability to discriminateevents and adequate calibration. The discrimination ability between both scores was not significant.Introducción: El Cardiac and Comorbid Conditions - Heart Failure (3C-HF) y el Meta-Analysis Global Group in Chronic HeartFailure (MAGGIC) son dos sistemas de puntaje desarrollados para predecir la mortalidad en pacientes con insuficiencia cardíaca(IC). El desempeño de estos puntajes ha sido poco estudiado en nuestro medio.Objetivo: Evaluar el desempeño del 3C-HF y del MAGGIC para predecir la mortalidad al año en una población de pacientescon IC.Material y métodos: Se incluyeron pacientes con diagnóstico de IC ambulatorios y dados de alta luego de una internación porIC aguda atendidos en dos centros. Se calcularon los puntajes 3C-HF y MAGGIC. Se evaluó como punto final la mortalidadglobal al año. La capacidad de discriminación de estos puntajes se analizó a partir del cálculo del área bajo la curva (ABC)ROC, y la calidad de su calibración, aplicando el test de Hosmer-Lemeshow. Se compararon ambas ABC mediante el test deHanley-Mc Neil.Resultados: Se incluyeron 704 pacientes con una edad promedio de 73 ± 11 años, el 39,6% eran mujeres. La mortalidad al añofue del 12,4% (n = 87). Ambos puntajes fueron predictores independientes de mortalidad, con HR de 1,03 (IC95% 1,008-1,06;p = 0,02) y 1,08 (IC95% 1,02-1,13; p = 0,004) para el puntaje 3C-HF y el MAGGIC, respectivamente. El 3C-HF presentó unABC de 0,70 (IC95% 0,64-0,75) y el MAGGIC de 0,67 (IC95% 0,61-0,73), sin diferencias entre las ABC (p = 0,41). Ambospresentaron adecuada calibración (p = 0,06 y p = 0,32, respectivamente).Conclusión: Los puntajes 3C-HF y MAGGIC fueron predictores de mortalidad a un año, con una moderada capacidad de discriminareventos y una adecuada calibración. No hubo diferencias en la capacidad de discriminación entre ambos puntajes