Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial.

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Cardiovascular risk in mild to moderately decreased glomerular filtration rate, diabetes and coronary heart disease in a southern European region.

INTRODUCTION AND OBJECTIVES: Individuals with mild to moderately decreased estimated glomerular filtration rate (eGFR=30-59 mL/min/1.73 m2) are considered at high risk of cardiovascular disease (CVD). No studies have compared this risk in eGFR=30-59, diabetes mellitus (DM), and coronary heart disease (CHD) in regions with a low incidence of CHD. METHODS: We performed a retrospective cohort study of 122 443 individuals aged 60-84 years from a region with a low CHD incidence with creatinine measured between January 1, 2010 and December 31, 2011. We identified hospital admissions due to CHD (myocardial infarction, angina) or CVD (CHD, stroke, or transient ischemic attack) from electronic medical records up to December 31, 2013. We estimated incidence rates and Cox regression adjusted subdistribution hazard ratio (sHR) including competing risks in patients with eGFR=30-59, DM and CHD, or combinations, compared with individuals without these diseases. RESULTS: The median follow-up was 38.3 [IQR, 33.8-42.7] months. Adjusted sHR for CHD in individuals with eGFR=30-59, DM, eGFR=30-59 plus DM, previous CHD, CHD plus DM, and CHD plus eGFR=30-59 plus DM, were 1.34 (95%CI, 1.04-1.74), 1.61 (95%CI, 1.36-1.90), 1.96 (95%CI, 1.42-2.70), 4.33 (95%CI, 3.58-5.25), 7.05 (5.80-8.58) and 7.72 (5.72-10.41), respectively. The corresponding sHR for CVD were 1.25 (95%CI, 1.06-1.46), 1.56 (95%CI, 1.41-1.74), 1.83 (95%CI, 1.50-2.23), 2.86 (95%CI, 2.48-3.29), 4.54 (95%CI, 3.93-5.24), and 5.33 (95%CI, 4.31-6.60). CONCLUSIONS: In 60- to 84-year-olds with eGFR=30-59, similarly to DM, the likelihood of being admitted to hospital for CHD and CVD was about half that of individuals with established CHD. Thus, eGFR=30-59 does not appear to be a coronary-risk equivalent. Individuals with CHD and DM, or eGFR=30-59 plus DM, should be prioritized for more intensive risk management.

[Long-term effects of intensive intervention on changes in lifestyle in patients with hyperfibrinogenaemia and moderate-high cardiovascular risk]. / Efectos a largo plazo de una intervención intensiva sobre cambios en los estilos de vida en pacientes con hiperfibrinogenemia y riesgo cardiovascular moderado-alto.

OBJECTIVES: To determine whether the benefit on cardiovascular risk factors (CVRF) persists 5 years after an intensive intervention in lifestyle (LS) that lasted 2 years, in patients with hyperfibrinogenaemia and moderate or high cardiovascular risk. DESIGN: multicentre prospective observational study. LOCATION: 13 Primary Care Centres in Barcelona and Baix Llobregat. PARTICIPANTS: A total of 300 patients who completed the EFAP study (146 intervention group, 154 control group). INTERVENTIONS: The EFAP study, conducted on patients with normal cholesterol and elevated fibrinogen showed that lifestyle interventions are effective in reducing CVRF. After the EFAP study, the 2 groups followed the usual controls, and re-assessed after 5 years. MAIN MEASUREMENTS: Age, gender, cardiovascular diseases (CVD) (diabetes, dyslipidaemia, hypertension, obesity), laboratory parameters (fibrinogen, glucose, full blood count, cholesterol, triglycerides), blood pressure, weight, height, body mass index (BMI), tobacco and alcohol use, REGICOR. RESULTS: At 5 years, the intervention group had a lower abdominal circumference (98 and 101cm, respectively, P=.043), a lower weight (76.30 and 75.04kg, respectively, P<.001), and BMI (29.5 and 30.97kg/m2, P=.018). Fibrinogen level was lower in the intervention group (330.33 and 320.27 mg/dl respectively, P < .001), and REGICOR risk was also lower in the intervention group (5.65 and 5.59 respectively, P < .06). CONCLUSION: The benefit of an intensive intervention in LS for 2 years to reduce CVRF persists at 5 years, but decreases its intensity over time. It is recommended to repeat the interventions periodically to maintain the beneficial effect on LS.

The association between education and cardiovascular disease incidence is mediated by hypertension, diabetes, and body mass index.

Education and cardiovascular disease (CVD) are inversely associated but the mediating factors have not been totally elucidated. Our aim was to analyze the mediating role of modifiable risk factors. Cohort study using the REGICOR population cohorts. Participants without previous CVD were included (n = 9226). Marginal structural models were used to analyze the association between education and CVD incidence at 6 years of follow-up. Mediation by modifiable risk factors (diabetes, dyslipidemia, hypertension, smoking, body mass index, and physical activity) was assessed using the counterfactual framework. Participants with a university degree had a CVD incidence hazard ratio (HR) of 0.51 (95% confidence interval (CI) = 0.30, 0.85), compared to those with primary or lower education. Only hypertension, BMI, and diabetes mediated the association between education and CVD incidence, accounting for 26% of the association (13.9, 6.9, and 5.2%, respectively). Sensitivity analyses showed that hypertension was the strongest mediator (average causal mediation effect [95% CI] = increase of 2170 days free of CVD events [711, 4520]). The association between education and CVD incidence is partially mediated by hypertension, BMI, and diabetes. Interventions to decrease the prevalence of these risk factors could contribute to diminish the CVD inequalities associated with educational level.

Chronic kidney disease in hypertensive subjects ≥60 years treated in Primary Care. / Enfermedad renal crónica en individuos hipertensos ≥60 años atendidos en Atención Primaria.

BACKGROUND: Hypertension (HT) is the second leading cause of kidney failure. In hypertensive patients with chronic kidney disease (CKD), blood pressure (BP) control is the most important intervention to minimise progression. For CKD diagnosis, standardised creatinine and estimated glomerular filtration rate (eGFR) testing by CKD-EPI is recommended. OBJECTIVES: To describe the prevalence and factors associated with a moderate decrease in eGFR (by CKD-EPI) and BP control in subjects with HT. METHODS: Cross-sectional descriptive study in subjects ≥ 60 years included in the SIDIAP plus database with hypertension and standardised serum creatinine and BP tests in the last 2years. EXCLUSION CRITERIA: eGFR<30, dialysis or kidney transplantation, prior cardiovascular disease, home care. Primary endpoint: eGFR by CKD-EPI formula. Covariates: demographic data, examination, cardiovascular risk factors, heart failure and auricular fibrillation diagnosis, and drugs (antihypertensive agents acting on renal function, antiplatelet and lipid lowering agents). BP control criteria: ≤130/80mmHg in individuals with albuminuria, ≤140/90 in all other subjects. RESULTS: Prevalence of eGFR <60=18.8%. Associated factors: age, gender, heart failure, albumin/creatinine ratio, auricular fibrillation, smoking, dyslipidaemia, diabetes and obesity. BP control: 66.14 and 63.24% in eGFR≥60 and eGFR <60, respectively (P<.05). Exposure to drugs was higher in eGFR<60. CONCLUSION: One in 5hypertensive patients without cardiovascular disease ≥60 years in primary care presented with a moderate decrease in eGFR. In addition to age and sex, albuminuria and heart failure were the main associated factors. Despite the increased exposure to drugs, BP control was lower in CKD.

[Compliance with recommendations in secondary prevention of stroke in primary care]. / Seguimiento de las recomendaciones en prevención secundaria cerebrovascular en atención primaria.

OBJECTIVE: Knowing compliance with secondary prevention recommendations of stroke in primary care and to identify factors associated with compliance. DESIGN: Multi-centre cross-sectional. SETTING: Health primary care centres in a metropolitan area (944,280 inhabitants). PARTICIPANTS: Patients aged 18years and over with ischemic brain disease diagnosis prior to 6months before the study. MAIN MEASUREMENTS: Clinical history records of demographic variables, risk factors and cardiovascular comorbidity, drugs, blood pressure values (BP), LDL-cholesterol and medical visits by doctor and nurses after the event. Good adherence was considered when BP <140/90 mmHg, LDL-cholesterol <100 mg/dL, smoking abstention and preventive drugs prescription (anti-platelet/anticoagulants, statins and angiotensin-converting-enzyme inhibitors/angiotensin-receptor-antagonists or diuretics) during the last 18months. RESULTS: A total of 21,976 patients, mean age 73.12 years (SD: 12.13), 48% women, 72.7% with stroke. Co-morbidity: hypertension 70.8%, dyslipidemia 55.1%, DM 30.9%, atrial fibrillation 14.1%, ischemic heart disease 13.5%, chronic renal failure 12.5%, heart failure 8.8%, peripheral arterial disease 6.2%, dementia 7.8%. No record was found for smoking in 3.7%, for BP in 3.5% and for LDL in 6.5%. Optimal control: abstention smoking in 3.7%, BP <140/90 in 65.7% and LDL <100 mg/dL in 41.0%. TREATMENT: 86.2% anti-platelet/anticoagulants, 61.3% statins and 61.8% angiotensin-converting-enzyme inhibitors, angiotensin-receptor-antagonists or diuretic. Registration and risk factors control was higher in 66-79years aged and lower in 18-40years aged. CONCLUSIONS: The implementation of clinical guidelines recommendations for stroke prevention in primary care must be improved, especially among younger population. Organizational changes and more active involvement by professionals and strategies against therapeutic inertia must be taken.