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

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

Vivenciando um mundo de procedimentos e preocupações: experiência da criança com Port-a-Cath Vivenciando un mundo de procedimientos y preocupaciones: experiencia del niño con Port-a-Cath A world of procedures and worries: experience of children with a Port-a-Cath

OBJETIVOS: Compreender como é para a criança com câncer a vivência de ser portadora de Port-a-Cath a partir de suas manifestações numa sessão de Brinquedo Terapêutico Dramático e propiciar a ela um meio de alívio. MÉTODOS: Estudo descritivo qualitativo realizado com seis crianças escolares e uma adolescente, cujos dados foram coletados numa sessão de Brinquedo Terapêutico Dramático e submetidos à análise qualitativa de conteúdo. RESULTADOS: Permitiram compreender que os procedimentos intrusivos geram ansiedade, preocupação, medo e dor às crianças, assim como que elas reconhecem a importância dos procedimentos, dos medicamentos, da realização dos exames físico e laboratoriais para o tratamento; reconhecem as vantagens da utilização do Port-a-Cath, mas que sua utilização é fonte de ansiedade, limitações e preocupações, especialmente as relacionadas ao risco de infecção, e que se sentiram felizes, confortadas e fortalecidas com o brincar. CONSIDERAÇÕES FINAIS: Os enfermeiros precisam estar preparados para assistirem a essas crianças integralmente e para utilizarem sistematicamente o Brinquedo Terapêutico como instrumento de comunicação e intervenção de enfermagem.<br>OBJETIVOS: Comprender cómo es para el niño con cáncer la vivencia de ser portador de Port-a-Cath a partir de sus manifestaciones en una sesión de Juego Terapéutico Dramático y propiciarle un medio de alivio. MÉTODOS: Estudio descriptivo cualitativo realizado con seis niños escolares y una adolescente, cuyos datos fueron recolectados en una sesión de Juego Terapéutico Dramático y sometidos al análisis cualitativo de contenido. RESULTADOS: Se pudo comprender que los procedimientos intrusivos generan ansiedad, preocupación, miedo y dolor a los niños, así como que ellos reconocen la importancia de los procedimientos, de los medicamentos, de la realización de los exámenes físico y de laboratorio para el tratamiento; reconocen las ventajas de la utilización del Port-a-Cath, pero que su utilización es fuente de ansiedad, limitaciones y preocupaciones, especialmente las relacionadas al riesgo de infección, y que se sentieron felices, confortadas y fortalecidas con el hecho de jugar. CONSIDERACIONES FINALES: Los enfermeros necesitan estar preparados para asistir a esos niños integralmente y para utilizar sistemáticamente el Juego Terapéutico como instrumento de comunicación e intervención de enfermería.<br>OBJECTIVES: To understand the experience of children with cancer who have a port-a-cath using a session of therapeutic instructional play to decrease children worries and anxieties. METHODS: Descriptive qualitative study with 6 children and 1 teenager. Data were collected through a session of therapeutic play and analyzed through content analysis. RESULTS: Invasive procedures generated children's anxiety, worry, fear, and pain. The children recognized the need of medical procedures, medications, physical examinations, and laboratory tests. In addition, they also recognized the advantage of the use of the port-a-cath; however, its use was a source of anxiety and worries, especially in regard to infections. The use of therapeutic play made them happier, comfortable, and feeling stronger. FINAL CONSIDERATIONS: Nurses need to be prepared to fully care for children with cancer who have a port-a-cath and to systematically use therapeutic play as a useful strategy for nursing communication and intervention