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

Protocol for monitoring tropical forest restoration: Perspectives from the atlantic forest restoration pact in Brazil

Monitoring protocols are needed to evaluate the millions of hectares of land that are being proposed for forest restoration in the coming decades. Standardized proposals are critical to evaluate efficacy of restoration strategies, identify triggers for corrective actions, compare results across projects, and generally learn from past projects to inform future restoration efforts. We describe an iterative process, including over 200 stakeholders, to develop a protocol for monitoring Brazilian Atlantic Forest restoration. We give an overview of the ecological, socioeconomic, and management criteria, indicators, and metrics included in the protocol. Strengths of the protocol include the following: (a) testing and use across sites with a range of ages, forest types, past land uses, restoration techniques, and implementing institutions; (b) participation by a broad range of government, nongovernment, private, and academic institutions in the protocol development process; and (c) inclusion of socioeconomic and management criteria. Next steps for facilitating the broad adoption of the protocol in the Atlantic Forest region include providing in person and online training courses, establishing an online repository for storing and comparing monitoring data, and developing smartphone applications to facilitate data collection. Although the protocol was developed for the Atlantic Forest context and further refinements are needed, we think that the Atlantic Forest Pact monitoring protocol may serve as a model to inform the development of similar protocols in other regions, which ultimately could be integrated to produce a pantropical protocol for common use by several restoration forest programs worldwide

Experiência de pais e outros familiares no cuidado à criança e ao adolescente após o transplante de medula óssea Experiencia de padres y otros familiares en el cuidado al niño y al adolescente después del transplante de medula ósea Experience of parents and other family members in the care to children and adolescents after bone marrow transplantation

O objetivo deste trabalho é descrever como os pais e outros familiares de crianças e adolescentes submetidos ao Transplante de medula Óssea (TMO) vivenciam esta experiência, especialmente na fase pós operatória. Participaram do estudo treze responsáveis por onze pacientes menores de dezoito anos. Utilizamos como instrumento de coleta de dados a entrevista semi-estruturada com os responsáveis. Para a análise dos dados recorremos a abordagem qualitativa. Através das entrevistas identificamos os seguintes temas: impacto do transplante e cotidiano familiar. Os resultados indicam que pela complexidade do TMO é indispensável o conhecimento da realidade familiar do paciente pois esta tem papel fundamental na sua qualidade de vida. Assim identificar condições, vivências e modo de vida das famílias permite trabalhar com base em suas reais necessidades, respeitando suas possibilidades e limites.<br>El objetivo de este trabajo es describir como los padres y otros familiares de niños y adolescentes sometidos al Transplante de Médula Ósea vivencian esa experiencia, especialmente después del transplante. Participaron del estudio trece responsables por once pacientes con menos de 18 años. Utilizamos como instrumento de recolección de datos la entrevista semi-estructurada con los responsables. Para el análisis de datos fue utilizado el abordaje cualitativo. A través de entrevistas fueron identificados los siguientes temas: impacto del transplante y cotidiano familiar. Los resultados indican que por la complejidad del Transplante de Médula Ósea es indispensable el conocimiento de la realidad familiar del paciente pues esta tiene un papel fundamental en su calidad de vida. Así, identificar condiciones, vivencias y el modo de vida de las familias permite trabajar con base en sus reales necesidades, respetando sus posibilidades y limites.<br>The purpose of this study is to describe how parents and other family members of children and adolescents submitted to Bone Marrow Transplantation, specially in the post operative period. Thirteen subjects responsible to the care of eleven patients under 18 years old participated in the study. Authors used semi-structured interviews to collected data. Data were analyzed through a qualitative approach. The following themes were identified: impact of transplantation and family life. Results indicated that due to the complexity of Bone Marrow Transplantation, the knowledge on the family reality is crucial as family plays a fundamental role in patients' quality of life. Therefore, to identify conditions, experiences and the life style of families enable the work based on their real needs, respecting their possibilities and limitations