Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.

Background: Management of low-density lipoprotein cholesterol (LDL-C) in Asia remains suboptimal, with ∼50% of patients who are treated with lipid-lowering therapies (LLTs) unable to achieve their guideline-recommended LDL-C goals. Asian-representative studies of the use of inclisiran are needed. Objectives: The authors sought to evaluate the efficacy and safety of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD, as an adjunct to diet and maximally tolerated statin dose, with or without additional LLTs. Methods: The ORION-18 was a phase 3 double-blind trial in which patients were randomized 1:1 to receive either 300 mg inclisiran sodium or matching placebo on days 1, 90, and 270. Percentage change in LDL-C from baseline to day 330 was the primary endpoint. Results: A total of 345 patients (mean age 59.5 years, mean baseline LDL-C 109 mg/dL, 74.7% male) were randomized to inclisiran or placebo. Baseline characteristics were similar in both groups. The percentage decrease in LDL-C from baseline to day 330 was 57.2% (P < 0.001); proprotein convertase subtilisin/kexin type 9 was reduced by 78.3% (P < 0.001). Time-adjusted percentage reduction in LDL-C from baseline after day 90 and up to day 360 was 56.3%. At day 330, 71.7% of participants with inclisiran achieved ≥50% reduction in LDL-C compared with 1.5% with placebo. Over the study period, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol (HDL-C) levels were decreased significantly, and HDL-C levels increased. The incidence of adverse events with inclisiran was similar to that with placebo. Conclusions: In Asian patients with ASCVD or high risk of ASCVD, inclisiran was effective and safe. (Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease [ASCVD] or ASCVD High Risk and Elevated Low-Density Lipoprotein Cholesterol [LDL-C] [ORION-18]; NCT04765657).

Efficacy, Safety, and Pharmacokinetics of Inclisiran in Japanese Patients: Results from ORION-15.

AIM: To evaluate the efficacy, safety, and pharmacokinetics (PK) of inclisiran in Japanese patients with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C). METHODS: ORION-15 was a phase 2, double-blind, placebo-controlled randomized trial. Patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), were randomized to inclisiran sodium 100, 200, or 300 mg, or placebo and dosed subcutaneously on Days 1, 90, and 270. The primary endpoint was the percentage change from baseline to Day 180 to demonstrate the superiority of inclisiran vs. placebo. Patients who consented to the PK substudy had additional study procedures for blood collection and safety assessment. RESULTS: Overall, 312 patients (mean age, 63.6 years; male, 74.4%; baseline LDL-C, 114.0 mg/dL) were randomized. Baseline characteristics were well balanced among the groups. At Day 180, inclisiran at all doses demonstrated significant LDL-C and proprotein convertase subtilisin/kexin type 9 (PCSK9) reductions (p＜0.0001 for both), which showed a dose-response relationship. The greatest reductions (LDL-C, 65.3%; PCSK9, 79.2%) were with inclisiran sodium 300 mg. At Day 180, ＞86% of the patients receiving inclisiran achieved the Japan Atherosclerosis Society 2017 lipid management targets compared to 8.9% for placebo. The mean (SD) plasma half-life for inclisiran was 6.8 (2.0)-7.6 (0.8) h. The incidence of adverse events with inclisiran was similar to that with placebo. CONCLUSION: Inclisiran sodium 100, 200, and 300 mg demonstrated clinically meaningful and statistically significant LDL-C and PCSK9 reductions at Day 180, which were consistent over 12 months. Inclisiran was effective and well tolerated in Japanese patients with hypercholesterolemia, including HeFH.

COVID-19 and long-term care facilities in Mexico: a debt that cannot be postponed.

Since the emergence of the COVID-19 pandemic, the most affected population group has been that of older people living in long-term care facilities (LTCFs), which has accumulated between 30 and 60 % of total number of deaths in the world. In Mexico, outbreaks have been reported in LTCFs of at least eight states. Various factors make this population group and LTCFs susceptible to COVID-1 outbreaks, mainly due to coexistence in common spaces, shared bedrooms and permanent physical contact with the personnel who work there, coupled with a lack of protocols and standards of care of mandatory observance, as well as personnel training limitations. There is evidence of the need to formally develop a National Care System that provides support to those in need of care and their families, and that includes LTCFs. In view of the challenges due to the lack of information and competencies in infection prevention and control at LTCFs, a group of experts, in collaboration with different public institutions, joined efforts with the purpose to update the guidelines in order to allow LTCFs face the pandemic and to contribute to the generation of said National Care System.

Ante la pandemia de COVID-19, el grupo más afectado ha sido el de las personas mayores que viven en instituciones de cuidados a largo plazo (ICLP), el cual ha acumulado entre 30 y 60 % de los fallecimientos en el mundo. En México se han reportado brotes en residencias de por lo menos ocho entidades federativas. Diversos factores hacen susceptibles a este grupo y a las ICLP: la convivencia en lugares comunes, dormitorios compartidos y el contacto físico con el personal que ahí labora, aunado a la falta de protocolos y estándares de cuidados de observancia obligatoria, así como a la escasa capacitación del personal. Se evidencia la necesidad de desarrollar un Sistema Nacional de Cuidados que brinde apoyo a las personas dependientes de cuidados y sus familias y que incluya a las ICLP. Derivado de los retos por la carencia de información y competencias en prevención y control de infecciones en las ICLP, un conjunto de expertos, en colaboración con instituciones públicas, integramos un grupo con el objetivo de actualizar las guías que permitan a las ICLP hacer frente a la pandemia y que contribuyan a la generación de ese Sistema Nacional de Cuidados.

COVID-19 e instituciones de cuidados a largo plazo en México: una deuda impostergable / COVID-19 and long-term care facilities in Mexico: a debt that cannot be postponed

Resumen Ante la pandemia de COVID-19, el grupo más afectado ha sido el de las personas mayores que viven en instituciones de cuidados a largo plazo (ICLP), el cual ha acumulado entre 30 y 60 % de los fallecimientos en el mundo. En México se han reportado brotes en residencias de por lo menos ocho entidades federativas. Diversos factores hacen susceptibles a este grupo y a las ICLP: la convivencia en lugares comunes, dormitorios compartidos y el contacto físico con el personal que ahí labora, aunados a la falta de protocolos y estándares de cuidados de observancia obligatoria, así como a la escasa capacitación del personal. Se evidencia la necesidad de desarrollar un Sistema Nacional de Cuidados que brinde apoyo a las personas con dependencia de cuidados y sus familias y que incluya a las ICLP. Derivado de los retos por la carencia de información y competencias en prevención y control de infecciones en las ICLP, un conjunto de expertos, en colaboración con instituciones públicas, integramos un grupo con el objetivo de actualizar las guías que permitan a las ICLP hacer frente a la pandemia y que contribuyan a la generación de ese Sistema Nacional de Cuidados.

Abstract Since the emergence of the COVID-19 pandemic, the most affected population group has been that of older people living in long-term care facilities (LTCFs), which has accumulated between 30 and 60 % of total number of deaths in the world. In Mexico, outbreaks have been reported in LTCFs of at least eight states. Various factors make this population group and LTCFs susceptible to COVID-1 outbreaks, mainly due to coexistence in common spaces, shared bedrooms and permanent physical contact with the personnel who work there, coupled with a lack of protocols and standards of care of mandatory observance, as well as personnel training limitations. There is evidence of the need to formally develop a National Care System that provides support to those in need of care and their families, and that includes LTCFs. In view of the challenges due to the lack of information and competencies in infection prevention and control at LTCFs, a group of experts, in collaboration with different public institutions, joined efforts with the purpose to update the guidelines in order to allow LTCFs face the pandemic and to contribute to the generation of said National Care System.

Use of the Spanish Version of the Rapid Geriatric Assessment in Mexican Patients in Long-Term Care.

We report our experience with the use of a Spanish version of the rapid geriatric assessment of 30 patients in 2 long-term care institutions in Mexico City by a group of healthcare students without prior experience in geriatric medicine. The Spanish version of the rapid geriatric assessment is a very easy tool to administer that can provide overall good results for identifying frailty, sarcopenia, anorexia, weight loss, and cognitive impairment.

Giant cell arteritis in Mexican patients.

BACKGROUND: Giant cell arteritis (GCA) is the most common primary systemic vasculitis worldwide, although it seems to be very rare in some areas, such as Latin America. OBJECTIVES: The objective of the study was to describe the clinical, laboratory, and treatment features in a Mexican Mestizo population with GCA. METHODS: Retrospective data chart review (1989-2010). RESULTS: Twenty-two patients with GCA were identified, 18 women and 4 men. Mean age was 73 (SD, 7.9) years. Diagnosis was made at a mean of 67 (SD, 83.6) days from symptom onset. Most frequent presenting symptoms included headache (90%), constitutional symptoms (86%), and polymyalgia rheumatica (59%). Severe cranial ischemic complications were present in 32%. Amaurosis fugax and blindness were present in 36% and 27%, respectively. High erythrocyte sedimentation rate was present in 89% of patients. Rapid response to prednisone treatment was seen, but in 10 patients, relapse occurred, possibly related to fast tapering. Additional treatment was methotrexate (n = 8), azathioprine (n = 5), and cyclophosphamide (n = 3). Median follow-up was 242 (SD, 214) weeks. CONCLUSIONS: Giant cell arteritis is rarely recognized in Latin America. We report on characteristics of GCA in a population of Mexican Mestizos, as ours is the largest series to be reported from Latin America so far. When compared with other series, age at onset is similar, females are more affected, and although a good response to corticosteroid treatment was seen, a higher frequency of amaurosis fugax and blindness was observed, accounting for an unfavorable functional outcome in 6 (27%) of 22 patients.