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

Fatores determinantes da carga de trabalho em uma unidade básica de saúde Decisive factors relating to workload in a primary healthcare unit

As doenças decorrentes do exercício pro-fissional, sejam de ordem física ou emocional, têm apresentado aumento crescente na sociedade atual, nos diferentes segmentos laborativos, com projeção significativa junto aos profissionais da saúde como médicos, dentistas, enfermeiros, auxiliares de enfermagem e auxiliares administrativos envolvidos com a prestação de serviços nas unidades de saúde. Este estudo teve por objetivo conhecer a carga de trabalho e seus fatores determinantes, buscando identificar possíveis relações entre as condições de trabalho e o possível impacto para a saúde dos trabalhadores. Participaram da amostra 31 indivíduos: 12 médicos, 3 dentistas, 1 enfermeira, 9 auxiliares de enfermagem, 3 auxiliares odontológicos e 3 auxiliares administrativos de uma Unidade Básica de Saúde (UBS) no interior de São Paulo. Para a coleta dos dados foi elaborado um roteiro de entrevista estruturado e realizadas reuniões com os grupos específicos para uma descrição detalhada das atividades realizadas em cada setor e o levantamento de problemas e de características desejáveis. Os resultados indicam a presença de carga física, carga cognitiva e carga psíquica; processo de comunicação inadequado; equipamentos obsoletos; número excessivo de usuários e estrutura frágil para lidar com absenteísmo.<br>Work-related diseases o either physical or emotional origin have been on the increase in contemporary society in the different work sectors. They have had a profound impact on health professionals, such as physicians, dentists, nurses, nursing assistants and administrative assistants in the primary healthcare units. This study aimed to establish the decisive factors relating to workload, seeking to identify possible relations between the working conditions and their potential impact on worker health. Thirty-one individuals comprised the sample, namely 12 physicians, 3 dentists, 1 nurse, 9 nursing assistants, 3 dental assistants and 3 business assistants at a PHU (Primary Healthcare Unit) in a city in the interior of the State of São Paulo. For the data collection, structured interviews were conducted through meetings with the specific groups of workers, such that a detailed description of the activities performed by each group could be drafted, as well as a survey of the problems and desirable features involved. The results indicated the presence of physical, cognitive and psychological demands; inadequate communication processes; obsolete equipment; excessive number of users and an inefficient structure to deal with absenteeism

Relacionamento probabilístico: recuperação de informações de óbitos infantis e natimortos em localidade no Maranhão, Brasil Probabilistic record linkage: recovery of data on infant deaths and stillbirths in Maranhão State, Brazil

Neste estudo utilizou-se método do relacionamento probabilístico de registros para estimar o sub-registro das informações sobre natimortos e óbitos infantis no Estado do Maranhão, Nordeste do Brasil, em 2008. Relacionaram-se os registros do Sistema de Informações Hospitalares (SIH) (N = 374.418) e do Sistema de Informações de Mortalidade (SIM) (N = 26.597), com utilização de softwares para extração, identificação e processamento dos dados. Observou-se sub-registro de 9,7% de natimortos, 12,0% de óbitos neonatais e 5,3% de pós-neonatais. Nos municípios maiores a correção do coeficiente de mortalidade infantil foi superior a 19%. A superioridade de informações de óbitos infantis do SIH foi de 6,5% (municípios < 25 mil habitantes), 2,0% (municípios de 25-80 mil habitantes) e 8,3% (municípios > 80 mil habitantes). As inconsistências ocorreram por não preenchimento de variáveis, informações discordantes para um mesmo evento e ausência completa de registro do óbito. O método utilizado mostrou-se útil para recuperação de dados de óbitos para o SIM a partir do SIH.<br>This study used probabilistic record linkage to estimate underreporting of stillbirths and infant deaths in Maranhão State, Northeast Brazil, in 2008. Records were linked between the Hospital Information System (SIH) (N = 374,418) and the Mortality Information System (SIM) (N = 26,597), using data extraction, identification, and processing software. Under-recording rates were 9.7% for stillbirths, 12% for neonatal deaths, and 5.3% for post-neonatal deaths. In the larger municipalities, the correction of the infant mortality rate was greater than 19%. The superiority of information on infant deaths in the SIH (as compared to the SIM) was 6.5% in municipalities with < 25 thousand inhabitants, 2% in municipalities with 25-80 thousand inhabitants, and 8.3% in those with > 80 thousand inhabitants. Inconsistencies involved non-completion of items/variables, discordant data on the same event, and in some cases even total absence of death records. The method proved useful for retrieving mortality data for the SIM from the SIH

Risk categorization using New American College of Cardiology/American Heart Association guidelines for cholesterol management and its relation to alirocumab treatment following acute coronary syndromes

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402