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

Detecting latent terrorist communities testing a gower\u2019s similarity-based clustering algorithm for multi-partite networks

Finding hidden patterns represents a key task in terrorism research. In light of this, the present work seeks to test an innovative clustering algorithm designed for multi-partite networks to find communities of terrorist groups active worldwide from 1997 to 2016. This algorithm uses Gower\u2019s coefficient of similarity as the similarity measure to cluster perpetrators. Data include information on weapons, tactics, targets, and active regions. We show how different dimensional weighting schemes lead to different types of grouping, and we therefore concentrate on the outcomes of the unweighted algorithm to highlight interesting patterns naturally emerging from the data. We highlight that groups belonging to different ideologies actually share very common behaviors. Finally, future work directions are discussed

A habilidade de atenção auditiva sustentada em crianças com fissura labiopalatina e transtorno fonológico Sustained auditory attention ability in children with cleft lip and palate and phonological disorders

OBJETIVO: Verificar a habilidade de atenção auditiva sustentada em crianças com fissura labiopalatina e transtorno fonológico, comparando o desempenho com crianças com fissura labiopalatina e ausência de transtorno fonológico. MÉTODOS: Dezessete crianças com idade entre 6 e 11 anos, com fissura labiopalatina transforame unilateral operada e ausência de queixa e/ou alteração auditiva, separadas em dois grupos: GI (com transtorno fonológico) e GII (com au&#349;encia de transtorno fonológico). Para detecção de alteração auditiva foram realizadas audiometria e timpanometria. Para avaliação fonológica foram utilizados os seguintes instrumentos: Teste de Linguagem Infantil e Consciência Fonológica: Instrumento de Avaliação Sequencial. Para avaliar a habilidade de atenção auditiva foi aplicado o Teste da Habilidade de Atenção Auditiva Sustentada. RESULTADOS: Das sete crianças com transtorno fonológico (41%), duas (29%) apresentaram alteração nos resultados do Teste da Habilidade de Atenção Auditiva Sustentada. Não houve diferença entre as crianças com fissura labiopalatina e transtorno fonológico e as crianças com fissura labiopalatina e ausência de transtorno fonológico quanto aos resultados do Teste de Habilidade de Atenção Auditiva Sustentada. CONCLUSÃO: A habilidade de atenção auditiva sustentada nas crianças com fissura labiopalatina e transtorno fonológico não difere da habilidade de atenção auditiva sustentada de crianças com fissura labiopalatina sem transtorno fonológico.<br>PURPOSE: To verify the ability of sustained auditory attention in children with cleft lip and palate and phonological disorder, in comparison with the performance of children with cleft lip and palate and absence of phonological disorder. METHODS: Seventeen children with ages between 6 and 11 years, with repaired unilateral complete cleft lip and palate and absence of auditory complaints or hearing problems, were divided into two groups: GI (with phonological disorder) and GII (absence of phonological disorder). Audiometry and tympanometry were carried out to detect hearing problems. To diagnose phonological disorder, the following instruments were used: Child Language Test, and Phonological Awareness: Instrument of Sequential Assessment. The ability of auditory attention was assessed using the Test of Sustained Auditory Attention Ability. RESULTS: From seven children with phonological disorder (41%), two (29%) had altered results in the Test of Sustained Auditory Attention Ability. There was no difference between children with cleft lip and palate and phonological disorder and children with cleft lip and palate and absence of phonological disorder regarding the results of the Test of Sustained Auditory Attention Ability. CONCLUSION: The sustained auditory attention ability in children with cleft lip and palate and phonological disorder do not differ from the sustained auditory attention ability of children with cleft lip and palate without phonological disorder