Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Guía Europea de Prevención Cardiovascular en la Práctica Clínica: adaptación Española del CEIPC 2008

Presentamos la adaptación española realizada por el CEIPC de la Guía Europea de Prevención de las Enfermedades Cardiovasculares (ECV) 2008. Esta guía recomienda el modelo SCORE de bajo riesgo para la valoración del riesgo cardiovascular. El objetivo es prevenir la mortalidad y morbilidad debidas a las ECV mediante el manejo de sus factores de riesgo en la práctica clínica. La guía hace énfasis en la prevención primaria y en el papel del médico y la enfermería de atención primaria en la promoción de un estilo de vida cardiosaludable, basado el incremento de los niveles de actividad física, la adopción de una alimentación saludable y, en los fumadores, el abandono del tabaco. La meta terapéutica para la presión arterial es en general <140/90 mmHg; pero en pacientes con diabetes, enfermedad renal crónica o ECV el objetivo es 130/80 mmHg. El colesterol debe mantenerse por debajo de 200 mg/dl (cLDL < 130 mg/dl); en los pacientes con ECV o diabetes el objetivo es cLDL < 100 mg/dl (80 mg/dl si factible en sujetos de muy alto riesgo). En diabetes tipo 2 y en pacientes con síndrome metabólico se debe reducir el peso y aumentar la actividad física y en su caso utilizar los fármacos indicados, para alcanzar los objetivos de IMC y de perímetro de cintura. El objetivo en diabéticos tipo 2 debe ser alcanzar una HbA1C < 7%. La amplia difusión de las guías y el desarrollo de los programas destinados a favorecer su implantación, identificando barreras y buscando soluciones, son objetivos prioritarios del CEIPC, como uno de los medios fundamentales para trasladar las recomendaciones establecidas a la práctica clínica diaria