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

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Variables asociadas al restablecimiento de la función ventricular luego de la revascularización miocárdica

Background: Myocardial revascularization is the treatment of choice in patients with ischemic systolic dysfunction. Left ventricular ejection fraction (LVEF) constitutes a prognostic factor in these patients, so it is of interest to identify the variables related with left ventricular function improvement. Objective: The aim of this study is to determine the variables associated with improvement of LVEF in patients with ischemic systolic dysfunction undergoing myocardial revascularization. Methods: Patients with LVEF 5% were analyzed. Results: The cohort consisted of 95 patients; 91.6% were men, mean age was 63 years, 40% were diabetic, 27% had previous myocardial infarction and LVEF was 36%±6%. Viability was assessed in 78% of cases. During the immediate postoperative period, 12.6% of patients presented ischemia and 28% low cardiac output. Multivariate analysis revealed that myocardial viability and lack of perioperative ischemia were independent predictors of LVEF improvement. Conclusions: Myocardial viability and absence of perioperative ischemia were associated with improved LVEF during long-term follow-up.Introducción: La revascularización miocárdica es el tratamiento de elección en pacientes con disfunción sistólica isquémica. La presencia de viabilidad miocárdica y otras variables son evaluadas al momento de decidir el tratamiento. Objetivos: Determinar las variables asociadas al restablecimiento de la fracción de eyección y el pronóstico a largo plazo, en pacientes con disfunción ventricular isquémica  sometidos a revascularización miocárdica. Materiales y Métodos: Se incluyeron pacientes con FEVI5%). Se realizó seguimiento clínico en busca de eventos cardiovasculares: insuficiencia cardíaca, muerte y eventos combinados. Resultados: Se incluyeron 95 pacientes, 91,6% masculinos, edad media de 63 años, 40% diabéticos, 27% con infarto previo y FEVI media de 36±6%. Se evaluó viabilidad en 78%. Durante el postoperatorio 12% presentaron isquemia perioperatoria y 28% bajo gasto cardíaco. Al seguimiento la tasa de muerte fue del 9,5% e insuficiencia cardíaca del 20%. La viabilidad (OR 0,182; 95% IC 0,057-0,578; p=0,004) y la ausencia de isquemia perioperatoria (OR 0,092; 95% IC 0,012-0,672; p=0,019) fueron predictores independientes de la mejoría de la FEVI. Al analizar el seguimiento según la FEVI post revascularización (Grupo I: no mejoría FEVI; Grupo II: mejoría FEVI) se evidenció menor tasa de eventos a favor del grupo II. El análisis de supervivencia determinó una significativa sobrevida en el grupo II (p=0,026). Conclusiones: La viabilidad y la falta de isquemia durante el perioperatorio se asociaron con mejoría de la FEVI durante postoperatorio alejado. Los pacientes sin mejoría presentan un pronóstico desfavorable al seguimiento

Valor pronóstico del tamaño del infarto de miocardio cuantificado mediante SPECT gatillada

Objetivos: Evaluar la utilidad de la cuantificación tamaño de infarto (TI) estimado por gated-SPECT en la predicción de complicaciones cardiovasculares en pacientes con un primer infarto agudo de miocardio (IAM). Material y métodos: Se analizaron los pacientes con IAM con elevación del ST desde 2009 a 2014, excluyéndose aquellos con IAM previo. El cálculo de TI se realizó mediante el software Cedars QPS. Se evaluaron eventos al año: insuficiencia cardíaca, arritmias ventriculares, muerte y la combinación de los tres.Resultados: Se incluyeron 149 pacientes, con edad media de 59±11 años y 81,9% de sexo masculino. El 16,1% eran diabéticos y 9,4% presentaron revascularización previa. El 84,6% ingresaron en Killip y Kimbal A, 43% fueron de territorio anterior y 69,8% fueron reperfundidos. La FEVI por gated-SPECT fue del 51±14%. Se realizó seguimiento clínico en el 95,9% de los casos. Se calculó el punto de corte del TI (curva ROC) para predecir eventos combinados al seguimiento en 22% (Sensibilidad: 92%, Especificidad: 81%, ABC: 0,94) y se dividió a la muestra en dos grupos: grupo I (TI<22%) y grupo II (TI≥22%). La prevalencia de eventos combinados fue mayor en el grupo II (2,1% vs. 50%; p<0,001). Se identificó como única variable predictora de eventos al seguimiento al TI ≥22% (OR 1,978; 95% IC 1,887-1,996; p<0,001). Conclusiones: La cuantificación precoz del TI mediante SPECT es un predictor independiente de riesgo al año que permite establecer una estratificación del riesgo en pacientes con un primer IAM

Effects of volenrelaxin in worsening heart failure with preserved ejection fraction: a phase 2 randomized trial

Relaxin is a peptide hormone that may decrease circulatory congestion and improve kidney function. In this study, we conducted a double-blind, international, multicenter trial to test whether volenrelaxin, a long-acting form of human relaxin, can improve left atrial (LA) function, reduce congestion and improve kidney function in patients with heart failure and preserved ejection fraction (HFpEF). We randomly assigned patients with New York Heart Association (NYHA) class II–IV HFpEF and recent heart failure (HF) decompensation to 25-mg, 50-mg or 100-mg volenrelaxin or placebo administered subcutaneously once weekly. The primary outcome was the change in LA reservoir strain at 26 weeks, with key secondary endpoints including changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR) and safety. The trial was stopped early by the sponsor because of evidence for worsening congestion after 332 participants had been enrolled (mean age 74 years, 49% women, mean body mass index 30.6 kg m−2, 31.9% NYHA class III–IV). Compared to placebo, 25-mg volenrelaxin improved LA reservoir strain (+3.9%, 95% confidence interval (CI): 1.1–6.6, P = 0.006) but did not have effects on this outcome at 50-mg (+1.3%, 95% CI: −1.3 to 3.9, P = 0.332) or 100-mg (+0.9%, 95% CI: −1.8 to 3.6, P = 0.521) doses. At 26 weeks, volenrelaxin (pooling all dosages) increased NT-proBNP levels (+24.5%, 95% CI: 2.0–51.8) and had no significant effect on eGFR (+2.2 ml min−1 1.73 m−2, 95% CI: −1.8 to 6.3). Volenrelaxin was also associated with a non-significant increase in risk for HF hospitalization compared to placebo (hazard ratio = 2.64, 95% CI: 0.93–7.56, P = 0.070), along with signals for an increased number of cardiovascular and renal serious adverse events (odds ratio = 2.52, 95% CI: 0.95–6.68, P = 0.056). In conclusion, despite some evidence for improvement in LA function at a low dose, treatment with this long-acting form of human relaxin was associated with worsening congestion in patients with recently decompensated HFpEF. ClinicalTrials.gov identifier: NCT05592275.<br/

Documento de Consenso sobre terapia antitrombótica en enfermedad coronaria del Comité de Cardiopatía Isquémica de la Federación Argentina de Cardiología

Los pacientes con cardiopatía isquémica se presentan en diferentes escenarios clínicos de la enfermedad coronaria, desde los síndromes coronarios agudos (con y sin elevación del segmento ST), síndromes coronarios crónicos y situaciones especiales definidas por la co-existencia de ciertos factores de riesgo (diabetes mellitus, enfermedad renal crónica, fibrilación auricular y otras), los cuales pueden requerir de diferentes pautas (o protocolos) de terapia antitrombótica. El objetivo principal de la terapia antitrombótica es el reducir los eventos isquémicos sin aumentar los riesgos, primordialmente complicaciones hemorrágicas, asociadas a este tipo de intervención. El objetivo de este artículo es ofrecer una revisión basada en la evidencia más recientes teniendo en cuenta las diferentes situaciones clínicas, así como un cuidadoso análisis del balance de beneficios y riesgos (reducción de eventos y complicaciones hemorrágicas, respectivamente) asociado con la terapia antitrombótica de los pacientes con enfermedad cardiovascular.Fil: Barcudi, Raúl Jesús. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola; ArgentinaFil: Bono, Julio. Sanatorio Allende; ArgentinaFil: Ramos, Hugo Roberto. Universidad Nacional de Córdoba; ArgentinaFil: Quiroga Castro, Walter. Instituto Modelo de Cardiología; ArgentinaFil: Muntaner, Juan. Universidad Nacional de Tucumán; ArgentinaFil: Macín, Stella. Universidad Nacional del Nordeste; ArgentinaFil: Zapata, Gerardo. Instituto Cardiovascular de Rosario; ArgentinaFil: Meiriño, Alejandro. Instituto Cardiovascular de Rosario; ArgentinaFil: Hominal, Miguel. Sanatorio Diagnóstico; ArgentinaFil: Mauro, Daniel. Instituto del Corazón San Rafael; ArgentinaFil: Atencio, Lorena. Instituto del Corazón San Rafael; ArgentinaFil: Fernández Murga, Arturo. Instituto de Cardiología; ArgentinaFil: Amoroso, Alejandro. Hospital San Bernardo; ArgentinaFil: Rengel, Esteban. Instituto de Cardiología; ArgentinaFil: Hasbani, Eduardo. Universidad Nacional de Tucumán; ArgentinaFil: Luciardi, Héctor. Universidad Nacional de Tucumán; ArgentinaFil: Zoni, César Rodrigo. Instituto de Cardiología JF Cabral; ArgentinaFil: Onocko, Mariela. Instituto de Cardiología JF Cabral; ArgentinaFil: Caruso, Orlando. Hospital Central de Mendoza; Argentin