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

Interpreting the Virtues of Mindfulness and Compassion: Contemplative Practices and Virtue-Oriented Business Ethics

The article aims to provide a standpoint from which to critically address two broad concerns. The first concern surrounds a naïve view of mindfulness, which takes it as a given that it is a good thing to cultivate mindfulness and attendant qualities like compassion because these virtues are key to improving the quality of life and bettering effective decisionmaking within business. Yet the virtue of mindfulness has roots in religious and spiritual traditions, and the virtue of compassion is complex and contextual; neither of these virtues operate in a vacuum. Nor do they function independently from other virtues and values. Reasonable people of goodwill possessing the virtues of mindfulness and compassion in good measure, may nevertheless strongly disagree about what the compassionate, mindful thing to do is, particularly in a business setting. It is, moreover, conceivable that intensively cultivating mindfulness and compassion could lead one to reject altogether the “dog-eat dog” culture of competitive business that draws upon selective features of mindfulness meditation that lie in the corporate comfort zone yet which are not especially countercultural from a religious or spiritual vantage point. The second concern is that Western virtue-based business ethics is largely confined to academic philosophical theories. As such, virtue-driven business ethics is often more centered around developing theoretical wisdom than developing “hard core” practical wisdom earned through yoga asanas, meditation, chanting, and breathing, whereas for contemplative practices the reverse is the case, with practical wisdom (“knowing how-to”) emphasized over theoretical wisdom (“knowing that”). Accordingly, the article examines prospects for cross-fertilization between, on the one hand, mindfulness and compassion interpreted as virtues in Eastern contemplative practices, and on the other hand, mindfulness and compassion as interpreted within Western virtue-oriented business ethics. Illuminating a pathway for such interpretative cross-pollination calls for an appropriate conceptual frame of reference that the article organizes around a set of interconnected themes. The first theme is that mindfulness and compassion represent key virtues within contemplative practices. This indicates a promising touchpoint between Eastern and Western traditions: their respective focus upon character, inner states, intrinsic motivation, and self-improvement toward ethicality in the world. The second theme is that such virtues in Eastern contemplative practices, as well as character traits integral to Western virtue-oriented approaches, denote contested “normative-interpretive” concepts that engage philosophical debate rather than indisputable empirical-criterial concepts that can be taken at face-value. The third theme advocates moving beyond behaviorist and neuropsychological accounts of virtue, approaching character traits of Eastern contemplative practice and Western virtue ethics through nonscientific inquiry into normative interpretive questions concerning such virtues (questions about meaning, responsibility, the nature of the self, reasons for acting). This supports debate over competing views of the nature, purpose, cultivation, and cultural context of mindfulness, compassion, and other virtues – issues arising as mindfulness enters the business management sphere -- to be conducted on normative grounds. With the background conceptual framework established, the article presents key points about the prospects for cross-fertilization between virtue ethics and contemplative practice, and why it matters, with reference to business ethics.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

CSR, Innovation and Human Resource Management. The Renaissance of Olivetti’s humanistic management in Loccioni Group – Italy

This paper addresses the theme of Corporate Social Responsibility (CSR) policies concerning labor and employees by proposing an anthropologically-centered analysis - developed from both the theoretical and empirical profiles - of business and leadership models that are geared toward a multidimensional development, which focuses on the valorization and promotion of the employee. The first part synthesizes the theoretical context in which the empirical analysis is found by proposing a literature review; while the second one analyses the business and leadership models, which have been successfully implemented by a medium-sized Italian firm - Loccioni Group - that is included among the “great place to work” on the national and international scale. This company has, for years, been distinguished for the best CSR-oriented practices regarding human resource management, innovation, environment and furthermore for its capability to “thread networks” with internal and external stakeholders, and is characterized by genuine commitment which is the result of an authentic and solid value-based system and a model of exemplary governance aimed at linking economic well-being, social cohesion and environmental protection. The case study offers an example of best stakeholders’ and employees’ management practices, which co-evolves with the environment, improving, at the same time, the company’s competitiveness and the socio-economic conditions of the local context in which it is deeply embedded. In this context, CSR is part of the DNA and widespread throughout the entire organization. Loccioni Group is an “extreme case” (although not unique in Italy) that is particularly significant and helps develop reflections on the importance of embracing the cultural and anthropological roots of CSR, which are connected to a model of humanistic management, and reinvent the Olivetti’s model of holistic development while conceiving the business as a tool for promoting social, economic, moral and environmental well-being