Clinical Practice Guidelines Research Articles

Survival and Toxicity Outcomes with Radiotherapy Technique and Timing in the Management of Wilms Tumor: a Systematic Review to Inform a National Clinical Practice Guideline Development

Purpose: Wilms tumor (WT) management has evolved into a multimodality paradigm that includes radiotherapy (RT), usually as an adjuvant or consolidative modality. Protocols are refined to maximize cure and compliance while minimizing acute toxicity and long-term effects. RT technique and timing are two factors that could improve these outcomes. We reviewed the evidence on survival and toxicity outcomes among WT patients with conventional versus advanced RT techniques and early versus delayed RT to inform a Department of Health (DOH) commissioned guideline. Materials and Methods: We systematically searched PubMed, EuropePMC, EBSCOHost, HERDIN, systematic review and clinical trial registries and official websites of scientific societies for relevant publications and grey literature. Eligibility screening, risk-of-bias assessment and data extraction were performed using a single-reviewer approach. Given the study and data heterogeneity, only a qualitative synthesis was performed. Certainty of evidence assessment was done using the GRADE approach. Results: We screened 314 studies and included seven in the review, including a phase 1/2 trial and six retrospective studies, all from first-world countries (US, France, Netherlands), except one from a newly industrialized country (Brazil). The certainty of evidence on the survival and toxicity outcomes with advanced RT techniques was very low. Moderate-certainty evidence supports that giving RT >14 days after surgery leads to increased mortality. Conclusion: Current evidence does not support the routine use of advanced RT techniques; proper contextualization is necessary. Tertiary centers managing WT should strive to administer RT within 14 days after surgery whenever possible. Keywords: Wilms tumor, nephroblastoma, radiotherapy, intensity-modulated radiotherapy, survival, toxicity

Update of clinical practice guidelines for the management of patients with sarcoma.

Update of clinical practice guidelines for the management of patients with sarcoma.

CAF to the Rescue! Potential and Challenges of Combination Antifungal Therapy for Reducing Morbidity and Mortality in Hospitalized Patients With Serious Fungal Infections.

The global burden of invasive fungal disease is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower and less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most invasive fungal diseases due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarized findings from animal models of CAF and assessed laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.

Implementation of Primary Immune Thrombocytopenia Clinical Practice Guidelines for Management of Pregnancy.

Background: Managing primary immune thrombocytopenia (ITP) in pregnancy is challenging. Providers must balance bleeding risk against medication toxicity. The evaluation of the implementation of pregnancy-specific ITP clinical guidelines has not been widely studied. The goal of this study was to describe the implementation of pregnancy-specific ITP guidelines at an academic health center. Methods: We conducted a retrospective chart review at the University of Oklahoma Health system from 2011 to 2020. Descriptive statistics were calculated to summarize the characteristics of the study population. Management, according to the clinical guidelines (American Society of Hematology; American College of Obstetricians and Gynecologists) was evaluated during pregnancy and during/for delivery. Results: A total of 85 pregnant persons with ITP were included. The majority (68%; 58/85) delivered vaginally. There were 0 maternal deaths and 2 infant deaths. No patients had major bleeding during pregnancy. Postpartum hemorrhage was experienced by 14%. The management of thrombocytopenia during pregnancy was 100% adherent to the strong recommendation for severe (n = 13) and mild (n = 11) thrombocytopenia. However, 18/50 (36%) asymptomatic persons with moderate thrombocytopenia received treatment despite the strong recommendation that treatment was unnecessary. Additionally, 8/21 (38%) persons with moderate thrombocytopenia received treatment to increase platelet counts for epidural anesthesia despite the guideline's suggestion that it was unnecessary. Conclusions: During pregnancy, patients with severe thrombocytopenia (i.e., most at risk of bleeding) received treatment. On the other hand, approximately 40% of pregnant persons with ITP received unnecessary treatment for moderate asymptomatic thrombocytopenia either during pregnancy or for an epidural. Utilizing clinical practice guidelines would reduce the overtreatment of pregnant persons which would reduce the potential side effects of therapy for the mother and infant.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on the Management of COVID-19: Anti-SARS-CoV-2 Neutralizing Antibody Pemivibart for Pre-exposure Prophylaxis.

This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019, developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody pemivibart as pre-exposure prophylaxis. The recommendation is based on evidence derived from a systematic review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Information on pemivibart is included in the U.S. Food and Drug Administration Emergency Use Authorization for this agent.

Egyptian pediatric kidney transplantation: highlights on post-transplant follow-up and management of complications by the Egyptian Pediatric Clinical Practice Guidelines Committee (EPG) Nephrology Group

BackgroundPediatric kidney transplantation is unique when compared to adults. They need optimum post-transplant care to achieve longer graft and patient survival. Infections, rejection, recurrence, malignancy, bone problems, hypertension, and surgical complications are the most important challenges that require prevention, early detection, and management. Chronic allograft nephropathy needs different approaches based on its related causes, allograft pathology, graft function, and availability of re-transplantation.Aim/objectivesThis national adapted guideline aims to frame evidence-based post-transplant recommendations adopted or adapted from EB source guidelines to optimize post-transplant patient care.MethodsOur guideline is evidence based adapted from four national and international source guidelines with permissions [KDIGO 2020, RA/BTS 2022–2018, EAU 2018] that were appraised with AGREE II instrument tool. We followed the “adapted ADAPTE” CPG formal adaptation methodology that consists of 3 phases and 24 steps and tools. Virtual monthly meetings all through the year 2023 were activated for reviewing and validation of final adaptation of evidence-based guideline draft, considering all comments of external reviewers. This guideline was registered in the practice guideline registration for transparency (PREPARE), number: PREPARE-2023CN364.ResultsRecommendation statements in guidelines stand for results in articles. Discussion of important recommendations and the rationale behind selection of adopted statements and tailoring of others to suit our local facilities, expertise, and renal native disease profile was presented in the text with reasons and references.ConclusionThe provided guidelines aim to improve graft and patient outcome through prevention and early management of complications and suggest research areas lacking validated research recommendations.

2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache

2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache

Practice guideline of influenza vaccination and antiviral drugs use in children(2024 editon)

Influenza is the most common acute respiratory infectious diseases among children in China. The annual seasonal influenza outbreak has a significant impact on children's health, poses a significant disease and socioeconomic burden, and arouses a wide public concern. In recent years, a number of new influenza vaccines and influenza antivirals have been approved for use in children, expanding the choices for prevention and treatment of influenza. Pediatric Infection Group, Chinese Society of Infectious Diseases of Chinese Medical Association and Infection Group, Pediatric Expert Committee of National Health Commission Capacity Building and Continuing Education, and China Clinical Practice Guidelines Alliance Methodology Committee organized a multidisciplinary guideline development group (GDG) consisting of experts in pediatrics, infectious diseases,epidemiologists,health policy,and guideline methodology proposed eight key issues concerning influenza vaccination and antiviral use from a practice perspective. Through research question construction, evidence retrieval and synthesis, evidence appraisal and evidence-to-decision discussion, recommendations and implementation suggestions were formulated. This guideline is intended to provide guidance for pediatricians at different facility levels and healthcare providers engaged in vaccination services,and institutional professionals dealing with prevention and control of infectious diseases.

Low-Value Clinical Practices in Pediatric Trauma Care

Reducing low-value care has the potential to improve patient experiences and outcomes and decrease the unnecessary use of health care resources. Research suggests that low-value practices (ie, the potential for harm exceeds the potential for benefit) in adult trauma care are frequent and subject to interhospital variation; evidence on low-value practices in pediatric trauma care is lacking. To estimate the incidence of low-value practices in pediatric trauma care and evaluate interhospital practice variation. A retrospective multicenter cohort study in a Canadian provincial trauma system was conducted. Children younger than 16 years admitted to any of the 59 provincial trauma centers from April 1, 2016, to March 31, 2022, were included. Low-value practices were identified from systematic reviews of clinical practice guidelines on pediatric trauma. The frequencies of low-value practices were evaluated by estimating incidence proportions and cases per 1000 admissions (low if ≤10% and ≤10 cases, moderate if >10% or >10 cases, and high if >10% and >10 cases) were identified. Interhospital variation with intraclass correlation coefficients (ICCs) were assessed (low if <5%, moderate if 5%-20%, and high if >20%). A total of 10 711 children were included (mean [SD] age, 7.4 [4.9] years; 6645 [62%] boys). Nineteen low-value practices on imaging, fluid resuscitation, hospital/intensive care unit admission, specialist consultation, deep vein thrombosis prophylaxis, and surgical management of solid organ injuries were identified. Of these, 14 (74%) could be evaluated using trauma registry data. Five practices had moderate to high frequencies and interhospital variation: head computed tomography in low-risk children (7.1%; 33 per 1000 admissions; ICC, 8.6%), pretransfer computed tomography in children with a clear indication for transfer (67.6%; 4 per 1000 admissions; ICC, 5.7%), neurosurgical consultation in children without clinically important intracranial lesions (11.6%; 13 per 1000 admissions; ICC, 15.8%), hospital admission in isolated mild traumatic brain injury (38.8%; 98 per 1000 admissions; ICC, 12.4%), and hospital admission in isolated minor blunt abdominal trauma (10%; 5 per 1000 admissions; ICC, 31%). In this cohort study, low-value practices appeared to be frequent and subject to interhospital variation. These practices may represent priority targets for deimplementation interventions, particularly as they can be measured using routinely collected data.

Patterns of Amphotericin B Use and Factors Related to Mortality in a Low-Middle Income Country: An Observational and Longitudinal Study

Background/Objectives: Amphotericin B is indicated in deep systemic fungal infections. The aim was to determine the sociodemographic, clinical and pharmacological variables of a group of Colombian patients treated with amphotericin B and factors associated with mo rtality. Methods: A longitudinal observational retrospective study on the use of amphotericin B in Colombia was conducted between January 2015 and December 2022. The multivariate analysis sought to identify variables related to mortality. Results: A total of 310 patients were identified, with a median age of 44.0 years, and 71.0% were women. Conventional amphotericin B was the most used (74.8%). The main uses were cryptococcosis (38.7%), histoplasmosis (31.9%) and candidiasis (29.4%). More than a third of patients died during hospitalization (40.3%). An increase in the Charlson Comorbidity Index score (HR: 1.13; 95% CI: 1.05–1.22) and in the qSOFA score (HR: 1.34; 95% CI: 1.04–1.73), coinfection by Mycobacterium tuberculosis (HR: 2.09; 95% CI: 1.32–3.31) and the requirement of vasopressors (HR: 4.20; 95% CI: 2.16–8.15) or invasive mechanical ventilation (HR: 2.73; 95% CI: 1.40–5.33) increased the probability of in-hospital death. In contrast, those who received systemic corticosteroids (HR: 0.43; 95% CI: 0.26–0.70) had a lower risk. Conventional amphotericin B is the most used drug mainly treating Cryptococcus neoformans infections. Conclusions: The use of amphotericin B was consistent with clinical practice guideline recommendations. In-hospital mortality was common, and factors such as increased comorbidities, higher qSOFA scores, coinfection with Mycobacterium tuberculosis and invasive procedures like mechanical ventilation were linked to increased mortality.

Osteonecrosis of the jaw in patients with clear cell renal cell carcinoma treated with targeted agents: a case series and large-scale pharmacovigilance analysis.

To optimize the use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for cancer patients, we characterized and evaluated ONJ related to TKIs and ICIs by analyzing a public database and reviewing the relevant literature. TKIs and ICIs are limited to drugs that treat renal cancer recommended by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for Kidney Cancer. We described a case series of patients experiencing ONJ while on TKIs or ICIs. We also analyzed spontaneous reports submitted to the FAERS in an observational and retrospective manner between January 2004 and December 2022. Selecting ONJ' adverse events to TKIs and ICIs. Associations between TKIs, ICIs and ONJ were assessed using reporting odds ratios (ROR), drug interaction signals based on the Ω shrinkage measure. 29 patients with ONJ events while on TKIs and ICIs were included in our case series. 240 were related to ONJ AEs. Specifically, 32.1% ICSRs were linked to sunitinib, 16.7% to lenvatinib, 12.9% to pazopanib, 12.5% to nivolumab, 10.0% to axitinib, 5.4% to sorafenib, 5.0% to pembrolizumab, 4.2% to cabozantinib, and 1.3% to ipilimumab. More ICSRs were generally seen in male and reported in Europe. The median age was 63years. Renal cancer and lung cancer was the most common indication for TKIs and ICIs, respectively. Excluding missing data, the prevalence of mortality was highest for sunitinib-related ONJ ICSRs (18.5%), followed by sorafenib-related ONJ ICSRs (15.4%). With the criteria of ROR, sunitinib and lenvatinib were significantly associated with ONJ AEs. With the criteria of Ω, nivolumab + cabozantinib was significantly associated with ONJ AEs. TKIs and ICIs have been reported to have significant ONJ side effects. Patients and physicians need to recognize and monitor these potentially fatal adverse events.

Diagnosis and Management of Obstructive Sleep Apnea: Updates and Review

Obstructive sleep apnea (OSA) is a heterogenous disease process that cannot be adequately categorized by AHI alone. There is a significant prevalence of OSA in the general population with ongoing efforts to evaluate the risk factors contributing to OSA and its associated clinical implications. Only by improving our understanding of OSA can we advance our methods in the diagnosis and treatment of OSA. For this article, the authors reviewed keywords of obstructive sleep apnea diagnosis and therapy in the databases of Embase, Medline, and Medline ePub over the past 3 years, excluding any articles that only addressed sleep apnea in children under age 17 years. This review article is divided into three main sections. First, we will investigate the use of novel screening tools, biomarkers, anthropometric measurements, and novel wearable technologies that show promise in improving the diagnosis of OSA. There is mention of comorbid conditions seen in OSA patients since certain disease combinations can significantly worsen health and should raise our awareness to diagnose and manage those concomitant disorders. The second section will look at the current and developing treatment options for OSA. These include positive airway therapy (PAP), mandibular advancement device (MAD), exciting new findings in certain medications, orofacial myofunctional therapy (OMT), hypoglossal nerve stimulation therapy (HGNS), and other surgical options. We will conclude with a section reviewing the current Clinical Practice Guidelines for Diagnostic Testing in Adults with Obstructive Sleep Apnea from 2017, which strongly advises polysomnography (PSG) or home sleep apnea testing (HSAT), along with comprehensive sleep evaluation for uncomplicated patients with a clinical presentation of OSA.

Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus (Version 2024).

The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus, developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019, serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China. As new evidence continues to emerge, it is essential to update these guidelines regularly to optimize clinical practice and research. To this end, the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association, in collaboration with multidisciplinary experts, have updated the guidelines based on the latest domestic and international research advancements and clinical practices, providing up-to-date guidance for clinicians and maternal and child healthcare workers.

Financial conflicts of interest among authors of clinical practice guideline for headache disorders in Japan

BackgroundFinancial relationships between clinical guideline authors and pharmaceutical companies introduce conflicts of interest (COI), potentially biasing guideline recommendations. Thus, proper management of COI is paramount for clinical guideline authors. Nevertheless, little is known about COI among neurology clinical guideline authors. This study aimed to evaluate the financial relationships between pharmaceutical companies and authors of Clinical Practice Guideline for Headache Disorders (CPGHD) in Japan.MethodsThis is a retrospective analysis of 2016–2020 personal payments data disclosed by all pharmaceutical companies affiliated with the Japan Pharmaceutical Manufacturers Association. We examined amounts and fraction of personal payments to all 57 CPGHD authors and all neurologists board-certified by the Japanese Society of Neurology. Payment data was descriptively analyzed at individual author level.ResultsAmong 57 CPGHD authors, 56 (98.3%) received personal payments totaling $2.7 million from pharmaceutical companies between 2016 and 2020. Median five-year payments were $89,955 for CPGHD authors, while $521 for board-certified neurologists. The CPGHD chairperson and vice chairperson received substantial payments during the guideline development period. Nevertheless, because of less rigorous and transparent COI policy compared to international standard policies, only 10 authors disclosed their financial relationships with the pharmaceutical companies in the guideline.ConclusionsMore than 98% of CPGHD authors received much higher personal payments from pharmaceutical companies than those to board-certified neurologists during the guideline development period in Japan.

Falsas creencias en torno al dolor. Consejos educativos breves en la consulta de atención primaria

In chronic non-oncological pain, there is a gap between the recommendations and the usual clinical practice. To improve this situation, it is essential to address unhelpful beliefs about pain in patients and health professionals. We address cultural beliefs such as thinking that pain means damage to the tissue where it is felt, that pain originates in the area where it is perceived, that it is important to rest for the tissues to heal, or that drugs and surgery are the best treatments for pain.First, professionals need to reflect on their own beliefs and question their own clinical practice: what do I believe about pain? Are these beliefs in line with current evidence? Do I follow the recommendations of clinical practice guidelines? In this way, by aligning their beliefs with the evidence, professionals will be able to begin to give appropriate educational advice to patients.

GRADE evidence to decision framework in genomics guidelines: systematic review &amp; appraisal

Abstract Background Transparent development of clinical practice guidelines (CPGs) is important for genomic medicine, as this field promises to partially challenge the traditional hierarchies of evidence. The GRADE Evidence to Decision (EtD) framework has recently emerged as a transparent and rigorous tool to produce recommendations. Our aim was to survey the genomic CPGs that used the GRADE EtD and appraise the applicability of its criteria and the quality of produced CPGs. Methods We systematically searched PubMed, Scopus, Web of Science and the gray literature till 2023 for relevant CPGs. From each eligible CPG, we extracted the reporting of the GRADE EtD criteria: benefits, harms, resource use, cost-effectiveness, acceptability, feasibility, equity and values. The quality of the CPGs were appraised across various domains using the (AGREE) II instrument. Results Among 1,144 records, 15 CPGs met inclusion criteria between 2018 and 2023, comprising 66 recommendations. Reporting of GRADE EtD criteria varied. Benefits, harms and their balance were addressed in approximately half of the recommendations 48% and 52% respectively. Feasibility, acceptability and values were also 52%, 47% and 40% respectively, resource use 39%, cost-effectiveness 23%. Equity was addressed in 36% of the recommendations. Quality appraisal of the CPGs also varied, domains were reported as follows: scope and purpose, clarity of presentation, editorial independence 86%, 85% and 84% respectively, rigor of development 77%, stakeholder involvement 72%, while applicability was 59%. Conclusions GRADE EtD is applied heterogeneously in genomic medicine CPGs, with difficulty in applying all of its criteria, including benefits and harms. Quality varied across domains with applicability of the CPGs less demonstrated. Key messages • Transparent approaches are needed in developing CPGs for genomic medicine. • Current genomic CPGs fail to address crucial aspects for producing recommendations, including benefits and harms.

Temporal trends in lipid management among Korean patients following acute myocardial infarction from 2011 to 2020

Abstract Background/Purpose Real-world data trends on dyslipidaemia prevalence and lipid management for patients following acute myocardial infarction (AMI) are lacking in South Korea, one of the Asia-Pacific nations. Our study aimed to evaluate the 10-year temporal trends of dyslipidaemia prevalence and lipid management in this patient population. Methods The study utilized datasets from two Korean AMI observational cohort (2011–2020) including a total of 26,751 participants (Figure 1A). The primary endpoints were as follows: (1) absolute low-density lipoprotein cholesterol (LDL-C) target of &amp;lt;70 mg/dL; (2) relative LDL-C target of &amp;gt;50% LDL-C reduction from the baseline; (3) absolute or relative LDL-C target (American target); and (4) both absolute and relative LDL-C targets (European target). Results The prevalence of dyslipidaemia increased from 11.1% to 17.1% (Table 1, Figure 1B), while the statin prescription rates increased from 92.9% to 97.0% from 2011 to 2020. High-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020 (Table 1) Interestingly, the yearlong substantial increases in the prescription rates of high-intensity statins were prominent between 2013 (21.9%) and 2014 (37.7%) and between 2018 (52.4%) and 2019 (66.1%), which may have been influenced by major revisions to the international lipid management guidelines and their adoption (Figure 1C). Ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The achievement rate of the absolute and relative LDL-C targets increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively (Table 1). The achievement rates of the American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) targets showed similar increasing trends (Table 1, Figure 1D). Conclusions Despite the adoption of lipid management guidelines in clinical practice has improved, some patients some patients are unable to reduce their LDL-C concentrations to their target levels. Our real-world analyses emphasise the need for multidirectional and continued efforts to optimise lipid management and improve the clinical outcomes in these patients.Figure 1

Differences in the optimization of pharmacological treatment in patients with heart failure and reduced ejection fraction and advanced chronic kidney disease

Abstract Introduction Chronic kidney disease is very prevalent in patients with HF, makes their treatment difficult and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate &amp;lt;30 mL/min/m2). Renal insufficiency increases the risk of drug intolerance and an increase in serious side effects, which can lead to underuse, with consequent negative effects on patient prognosis. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the achievement of dose targets for the most used drugs in HF with reduced ejection fraction (HFrEF) and the impact of advanced CKD. Methods We analyzed 914 patients with HFrEF consecutively included between 2019 and 2021 in the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology in 45 centers. We evaluated the proportion of patients treated with ACEI, ARA, ARNI, MRA, beta-blockers and SGLT2 inhibitors at the registry inclusion visit, the causes of non-prescription, and the achievement of the maximum dose recommended in the ESC clinical practice guidelines or the maximum tolerated dose in these patients, comparing the GFR groups, greater or less than 30 ml/min/m2. Results Of the 914 patients, 8.9% had a GFR&amp;lt;30 mL/min/m2. Their age was 76.9±9.7 years, 39.7% women, mean LVEF 32.8±9-6%. Patients with GFR&amp;lt;30 received in a significantly lower proportion all HF drugs except diuretics, ARBs and potassium chelators: sacubitril-valsartan 30.5% vs 59.2%; MRAs 31.7 vs 77.8%; SGLT2 inhibitors 34.1 vs 52.9% (p&amp;lt;0.001; Figure 1). The main reason for non-use was intolerance/contraindication for beta-blockers and "other" for the rest of the drugs (Figure 1). The proportion of patients in whom the maximum recommended, or maximum tolerated dose was reached was low in both groups, less than 40-50% for all drugs except MRA. There were no significant differences between the two groups in relation to the degree of renal dysfunction, although there was a tendency for the recommended doses to be obtained more frequently in the group with lower GFR (Figure 2). Conclusions In our contemporary cohort of real-life patients with HFrEF and advanced CKD, the use of recommended drugs for HF was significantly lower than in those patients with better renal function. However, where they were used, maximum recommended or tolerated doses were achieved in a higher proportion of patients. This indicates that with adequate selection it is possible to achieve the objectives proposed by the clinical practice guidelines in this complex group of patients.

Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study

Abstract Introduction Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events. Methods We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders. Results Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17). Conclusions In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome

Low-density lipoprotein cholesterol goal attainment with "inclisiran first" versus usual care in patients with atherosclerotic cardiovascular disease

Abstract Background Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC). Purpose To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C &amp;lt;70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC. Methods VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (&amp;lt;1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated. Results Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event &amp;lt;1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of &amp;lt;70 mg/dL and &amp;lt;55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively). Conclusions Participants with ASCVD and LDL-C &amp;gt;70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.