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

Diversidad genética de ovinos criollos colombianos

Ojective. genetical characterization the creole Colombian sheep and their relationships with breeds of European origins. Materials and methods. Blood samples of 261 sheeps from the following populations were collected: Criollos de Lana (CL), Mora Colombiana (MC), Criollo de Pelo (CP), criollos mestizos (Mes), Hampshire (Hamp), Corriedale (Corr), Katahdin (Kath), Pelibuey (Pel), in 40 farms of 8 departments (Córdoba, Magdalena, Cesar, Atlántico, Valle del Cauca, Nariño, Boyacá, Tolima) and 30 samples of Merino Spanish, Merino Precoz (MP), Merinofleischschaf (MF), Segureño (Seg) and Uda (UD) de Nigeria. A total of 15 microsatellites markers were included inthis study. Results. In creole sheep, the average number of alleles was found 6.20±1.48 (CL), 7.27±1.39 (CP) y 3.60±1.55 (MC); high genetic diversity found (high heterozygosities 75%), negative values in the FIS revealed high degree of introgression; furthermore the FST revealed genetic structure in both: Creole sheep (FST=0.02**) and departments (FST=0.039**).According to genetic distance, the creole Colombian sheep differs with outsider sheep. Conclusions. The results recommend protecting the Creole sheep production because it has been threatened by constant cross with foreign breeds, which would lead to the loss of genetic identity and adapting traits of creole sheep.themselves.Objetivo. Caracterizar genéticamente los ovinos criollos colombianos y sus relaciones con razas de origen europeo. Materiales y métodos. 261 muestras de sangre de las siguientes poblaciones, fueron colectadas: Criollos de Lana (CL), Mora Colombiana (MC), Criollo de Pelo (CP), mestizos (Mes), Hampshire (Hamp), Corriedale (Corr), Katahdin (Kath), Pelibuey (Pel), En 40 fincas de ocho departamentos (Córdoba, Magdalena, Cesar, Atlántico, Valle del Cauca, Nariño, Boyacá y Tolima) y 30 muestras de Merino Español (ME), Merino Precoz (MP), Merinofleischschaf (MF), Segureño (Seg) y Uda (UD) de Nigeria. Un total de 15 marcadores microsatélites fueron incluidos en este estudio. Resultados. En ovinos criollos, el número promedio de alelos encontrado fue 6.20±1.48 (CL), 7.27±1.39 (CP) y 3.60±1.55 (MC); hallándose también alta diversidad genética en ellos (heterocigosidades superiores al 75%), valores negativos en el FIS revelaron alto grado de introgresión; además el FST reveló estructura genética tanto en los grupos criollos (FST=0.02**), como en los departamentos muestreados (FST=0.039**). Según la distancia genética, los ovinos criollos colombianos presentan diferencias con los ovinos foráneos. Conclusiones. Los resultados obtenidos recomiendan proteger la ovinocultura criolla puesto que se encuentra amenazada por los constantes cruzamientos con razas foráneas, lo que conllevaría a pérdida de la identidad genética y de los rasgos de adaptación propios de los animales criollos

DETERMINACIÓN DE LA CURVA DE CRECIMIENTO EN OVINOS CRIOLLOS DE PELO, MEDIANTE LA UTILIZACIÓN DEL MODELO GOMPERTZ, EN EL TRÓPICO BAJO COLOMBIANO

En Colombia existe una diversidad de ovinos, denominados ovinos criollos, resultado del cruce de diferentes razas, desde la época de la colonización y que se adaptaron a diferentes regiones del país. En el caso particular de este estudio, se hace referencia a los ovinos criollos de pelo, que se acomodaron a las condiciones biogeográficas de la Costa Caribe colombiana. Estos animales, por su adaptabilidad, han tenido un importante papel en el desarrollo de la ovinocultura del país; sin embargo, es muy poca la información que se tiene, a nivel nacional, sobre las características crecimiento de la raza o especie. El objetivo del presente estudio fue determinar la curva de crecimiento de dos poblaciones de ovinos criollos del trópico bajo colombiano, a través del uso del modelo no lineal Gompertz. Se utilizaron 55 animales, con 13 pesajes cada uno, perteneciente a dos sistemas de producción del departamento de Córdoba, Colombia. Se realizó un ajuste del modelo, mediante el procedimiento NLIN de Statistical Analysis Software (SAS), para la estimación de los parámetros del modelo. Se estimó β0, β1 y β2, cuyos valores fueron 25,97 ± 9,3, 2,1 ± 0,5 y 0,010 ± 0,004, respectivamente. Los estimados de madurez a los 4 y 6 meses fueron de 55,8 y 70,6%, respectivamente, y la edad al 75 de madurez fue de 7,0 meses y al 95% de madurez, de 13,1 meses. El modelo de Gompertz permitió describir el crecimiento de ovinos criollos, en condiciones de pastoreo, en el trópico bajo

Growth curve determination for creole hair Sheep using the gompertz model in the low Colombian tropic

En Colombia existe una diversidad de ovinos, denominados ovinos criollos, resultado del cruce de diferentes razas, desde la época de la colonización y que se adaptaron a diferentes re-giones del país. En el caso particular de este estudio, se hace referencia a los ovinos criollos de pelo, que se acomodaron a las condiciones biogeográficas de la Costa Caribe colom-biana. Estos animales, por su adaptabilidad, han tenido un importante papel en el desarrollo de la ovinocultura del país; sin embargo, es muy poca la información que se tiene, a ni-vel nacional, sobre las características crecimiento de la raza o especie. El objetivo del presente estudio fue determinar la curva de crecimiento de dos poblaciones de ovinos criollos del trópico bajo colombiano, a través del uso del modelo no lineal Gompertz. Se utilizaron 55 animales, con 13 pesajes cada uno, perteneciente a dos sistemas de producción del departamento de Córdoba, Colombia. Se realizó un ajuste del modelo, mediante el procedimiento NLIN de Statistical Analysis Software (SAS), para la estimación de los paráme-tros del modelo. Se estimó β0,β1 y β2, cuyos valores fueron 25,97 ± 9,3, 2,1 ± 0,5 y 0,010 ± 0,004, respectivamente. Los estimados de madurez a los 4 y 6 meses fueron de 55,8 y 70,6%, respectivamente, y la edad al 75 de madurez fue de 7,0 meses y al 95% de madurez, de 13,1 meses. El modelo de Gompertz permitió describir el crecimiento de ovinos crio-llos, en condiciones de pastoreo, en el trópico bajo.The Colombian Creole sheep has an important role in the development of sheep farming in the country, as this breed is distributed in most of the territory, being animals with significant features that make it widely used in farms with different productive purposes. To assess growth characteristics in animals have been used mathematical models, which describe the relationship between the age of the animal, its rate of growth and maturity. These models are equations that allow the construction of continuous curves of one biological variable according to another. This study aimed to determine the growth curve of two populations of crossbred sheep through the use of nonlinear Gompertz model. 55 animals with 13 measures of weight each were used, pertaining to two production systems of the department of Córdoba, Colombia. Estimaste for β0, β1 y β2 were 25.97 ± 9.3, 2.1 ± 0.5 and 0.010 ± 0.004, respectively. Estimates of maturity at 4 and 6 months were 55.8 and 70.6%, respectively; age 75% of maturity was of 7.0 months and at 95% of maturity was of 13.1 months. Gompertz model allowed describing the growth of creole sheep in conditions of grazing in the low tropics.Incluye referencias bibliográfica

Effect of supplementation on weight gain and Carcass dressing of sudan lambs

Incluye referencias bibliográfica

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

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN