Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

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 < 100 mmHg (n = 1127), estimated glomerular filtration rate < 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

Síndrome metabólico en la mujer

Resumen: Introducción: La obesidad, especialmente la abdominal, se asocia con la resistencia al efecto de la insulina sobre la glucosa periférica y la utilización de ácidos grasos, hecho que puede conducir al desarrollo de síndrome metabólico y a la diabetes mellitus tipo 2. La resistencia a la insulina, la hiperinsulinemia y la hiperglucemia asociada, y el aumento de adipoquinas también puede llevar a la disfunción endotelial vascular, perfil anormal de lípidos, hipertensión e inflamación vascular, todo lo cual promueve el desarrollo de enfermedad cardiovascular aterosclerótica; a esa asociación se le conoce como síndrome x, cuarteto de la muerte, síndrome de resistencia a la insulina.En el estudio NHANES III, el síndrome metabólico estaba presente en el 5% de los pacientes de peso normal, 22% de los que tenían sobrepeso, y el 60% de aquellos que eran obesos. El aumento del peso corporal es un factor de riesgo importante para el síndrome metabólico, además de la edad y la raza, otros factores asociados con un mayor riesgo de síndrome metabólico, el consumo de bebidas endulzadas con azúcar y medicamentos antipsicóticos. Objetivo: Determinar cómo influye el síndrome metabólico en la mujer en el aumento de riesgo cardiovascular. Método: Se realizó una revisión sistemática de las investigaciones y de las revisiones de tema que se han realizado en últimos años sobre el síndrome metabólico en la mujer, a partir de los hallazgos arrojados de bases de datos científicas. Uptodate, PubMed y SciELO. Conclusiones: La enfermedad cardiovascular es la principal causa de muerte en las mujeres y existen factores de riesgo específicos de la mujer para desarrollarla, entre los cuales están: edad temprana de menarquia, menopausia, síndrome premenstrual, síndrome de ovario poliquístico, uso de anticonceptivos orales, haber presentado trastorno hipertensivo del embarazo, parto pretérmino y otros factores de riesgo compartidos con los hombres, como edad, antecedentes familiares, hipertensión arterial, dislipidemias, diabetes mellitus, síndrome metabólico, enfermedad renal crónica, tabaquismo, dieta, consumo de alcohol, sedentarismo, obesidad, factores psicosociales, marcadores inflamatorios, proteína C reactiva, concentración elevada de fibrinógeno plasmático e hiperhomocisteinemia. Abstract: Introduction: Obesity, especially abdominal obesity, is associated with resistance to the effect of insulin on peripheral glucose and the use of fatty acids. This can lead to the development of metabolic syndrome and type 2 diabetes mellitus, resistance to insulin, hyperinsulinemia and associated hyperglycemia, and adipokines. It can also lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. This association is known as syndrome X, the quartet of death, or insulin resistance syndrome.In the NHANES III study, metabolic syndrome was present in 5% of patients with normal weight, 22% of those who were overweight, and 60% of those who were obese. Increased body weight is a major risk factor for metabolic syndrome, in addition to age and race. Other factors associated with an increased risk of metabolic syndrome include the consumption of drinks sweetened with sugar and antipsychotic medications.In this review, we will discuss how metabolic syndrome affects women in increasing cardiovascular risk. Method: A systematic review of the research was carried out, with the subject reviews which have been carried out in recent years regarding metabolic syndrome in women, derived from scientific data bases. Uptodate, Pubmed and Scielo. Conclusions: Cardiovascular disease (CVD) is the main cause of death in women and there are risk factors which are specific to women, such as early onset of menarche, menopause, premenstrual syndrome, polycystic ovarian syndrome, the use of oral contraceptives, a history of pregnancy induced hypertension, and preterm delivery. Other risk factors are shared with men, such as age, family history, hypertension, dyslipidemias, diabetes mellitus, metabolic syndrome, chronic kidney disease, smoking, diet, consumption of alcohol, a sedentary lifestyle, obesity, psychosocial factors, C-reactive protein inflammatory markers, a high plasma fibrinogen level and hyperhomocysteinemia. Palabras clave: Síndrome metabólico, Mujer, Factores de riesgo, Keywords: Metabolic syndrome, Women, Risk factor

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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A Survey of Empirical Results on Program Slicing

International audienceBACKGROUND:Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS:This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS:Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION:Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

BACKGROUN