Episode 394: 402. Cardiovascular Risk Factors, Zilebesiran, Shared Decision Making

All of these articles have been talked about on questioning medicine social media on tik tok and instagram but here is an update of my recent reading

Buelt, Andrew | 2:13 PM (1 hour ago) |  | to mehttps://jamanetwork.com/journals/jama/fullarticle/2833338 Conclusions and Relevance  These results support use of metformin for treatment of symptomatic knee osteoarthritis in people with overweight or obesity. Because of the modest sample size, confirmation in a larger clinical trial is warranted.    Lee S et al. Live zoster vaccination and cardiovascular outcomes: A nationwide, South Korean study. Eur Heart J 2025 May 5; [e-pub]. (https://doi.org/10.1093/eurheartj/ehaf230) In a new South Korean study, researchers evaluated nearly 1.3 million people (age ≥50) who were entered into a nationwide database. In an analysis adjusted for numerous confounders and with an average follow-up of 6 years, people who received a VZV vaccine had significantly lower risk (by ≈25%) for overall adverse cardiovascular events, heart failure, cerebrovascular disorders, ischemic heart disease, thrombotic disorders, and arrhythmias.  https://pubmed.ncbi.nlm.nih.gov/40658956/ Conclusion: Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group.   https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0326804   We did not find that haloperidol was arrhythmogenic or increased mortality in these largely short-duration trials. Further research to clarify actual clinical outcomes related to QTPmeds is important to inform safe prescribing practices.

https://www.nejm.org/doi/10.1056/NEJMoa2504544  During follow-up ranging from 12 to 52 weeks, fewer patients had severe exacerbations in the albuterol/budesonide group than in the albuterol group (5% vs. 9%). Patients in the albuterol/budesonide group had less than half the total exposure to systemic glucocorticoids as those in the albuterol group (mean, 23 vs. 62 mg per year).   Clinical Practice: This study supports the use of an as-needed combination of albuterol and budesonide in reducing severe asthma exacerbations in patients with mild asthma who are inadequately controlled by SABA alone. This aligns with current recommendations by the Global Initiative for Asthma (GINA), which advocates for an inhaled corticosteroid plus a fast-acting bronchodilator as rescue therapy across all treatment steps for patients aged 12 years and older.   https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673625004398?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0140673625004398%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F  Clinical Recommendation: The findings support the practice of initiating DOAC treatment within 4 days of an acute ischemic stroke in patients with atrial fibrillation, as it reduces the risk of early recurrent ischemic stroke without increasing hemorrhagic complications. This challenges the traditional approach of delaying anticoagulation to avoid potential bleeding risks.   https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.074544?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org  reduce the necessity for surgical intervention. Clinical Recommendations: Given their proven cardiovascular benefits, safety profile, and cost-effectiveness, high-dose statins should be strongly considered for patients with small AAAs, particularly those without contraindications. Future Directions:

https://publications.aap.org/pediatrics/article/156/1/e2024070175/202234/Infant-Antibodies-After-Maternal-COVID-19?autologincheck=redirected  Objective:The study aimed to evaluate the kinetics and duration of maternally derived antibodies in infants up to 6 months old, following maternal COVID-19 vaccination during pregnancy or postpartum. Study Design:A prospective multicenter cohort study was conducted across nine U.S. academic sites, enrolling infants born to mothers vaccinated with 2- (n=280) or 3-dose (booster) monovalent mRNA vaccines during pregnancy (n=202) or postpartum (n=36). Primary Outcomes: Antibody Levels: Significantly higher geometric mean titers (GMTs) of binding and neutralizing antibodies (nAb) were observed at birth and 2 months in infants of mothers who received a booster dose during pregnancy compared to those who received 2 doses or were vaccinated postpartum. Sustained Antibody Levels: Higher titers against the vaccine strain persisted up to 6 months in infants of boosted mothers, although not for the Omicron BA.1 and BA.5 variants.    https://pubmed.ncbi.nlm.nih.gov/40478588/   Objective:The study aimed to determine if mailed self-collection kits for CCS, with or without additional patient navigation, could improve screening participation compared to standard telephone reminders. Study Design:This was a pragmatic, parallel, single-blinded, randomized clinical trial conducted within a publicly funded safety-net health system in Houston, Texas. It included 2474 participants who were overdue for CCS. Primary Outcomes: Participation Rates: Among those who received a telephone reminder and mailed self-collection, 41.1% participated in screening, compared to 17.4% who received a telephone reminder alone. When patient navigation was added to mailed self-collection, participation increased to 46.6%. Effectiveness: Self-collection kits significantly improved participation, with a relative participation of 2.36 times higher than telephone reminders alone. Adding patient navigation further modestly increased participation to 2.68 times higher.

https://www.nejm.org/doi/10.1056/NEJMoa2415879?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed Key Findings: Classic Risk Factors: The five risk factors examined were hypertension, hyperlipidemia, underweight and overweight or obesity, diabetes, and smoking. These factors are estimated to account for about 50% of the global burden of cardiovascular disease. Lifetime Risk Estimates: Among individuals free of these risk factors at age 50, the lifetime risk of cardiovascular disease was 13% for women and 21% for men. For those with all five risk factors, the lifetime risk jumped to 24% for women and 38% for men. Significance of Risk Factor Modification: Adjusting certain risk factors during midlife, particularly managing hypertension and quitting smoking, led to the most significant gains in life expectancy free of disease. For instance, controlling hypertension between ages 55 and 60 yielded the most additional life-years free of cardiovascular disease. Quitting smoking during the same period was associated with the most additional life-years free of death from any cause.    https://jamanetwork.com/journals/jama/fullarticle/2834632 Study Design: This was a phase 2, randomized, double-blinded trial with participants enrolled from 150 sites across 8 countries. The study spanned from January 2022 to June 2023, with analyses completed by March 2024. Participants received indapamide, amlodipine, or olmesartan as background therapy. Those with a specified range of 24-hour mean ambulatory systolic blood pressure (SBP) were then randomized to receive either a single subcutaneous dose of 600 mg zilebesiran or placebo. Efficacy Results: At 3 months, zilebesiran significantly reduced the 24-hour mean ambulatory SBP compared to placebo across all cohorts: Indapamide: -12.1 mmHg Amlodipine: -9.7 mmHg Olmesartan: -4.5 mmHg Similar reductions were observed in office SBP measurements at 3 months.    https://pubmed.ncbi.nlm.nih.gov/40578930/   Primary Outcomes: Discontinuation of Opioid Therapy: Patients in the greater SDM group were less likely to discontinue opioid therapy 3 months post-baseline compared to those in the lesser SDM group (Relative Risk: RR of 0.56). Opioid Prescribing Frequency: Over a 12-month period, patients in the greater SDM group experienced more frequent opioid prescriptions (RR of 1.24). Secondary Outcomes: Physical Function: Interestingly, physical function was slightly worse in the greater SDM group, but this difference was not deemed clinically significant. Back-related Disability: Both greater opioid use and SDM were associated with increased back-related disability and worse physical function, yet these findings were also not clinically significant. No significant SDM x opioid therapy interaction effects were observed, indicating that more frequent opioid use coupled with SDM did not lead to better patient outcomes in pain, function, or health-related quality of life (HRQOL).

https://pubmed.ncbi.nlm.nih.gov/40443569/ Candida hypertension guidelines start with Polly pill https://pubmed.ncbi.nlm.nih.gov/40562047/ Once weekly insulin equal to once daily insulin  https://www.jwatch.org/na58924/2025/06/26/new-single-pill-three-drug-combination-hypertension?query=etoc_jwhospmed&jwd=000020154104&jspc=HOS&cid=DM2406155_Subscriber&bid=-1280218728 FDA-approved new triple Polly pill https://pubmed.ncbi.nlm.nih.gov/40517008/ For carpal tunnel syndrome I do keep giving steroid injections  https://www.acpjournals.org/doi/10.7326/ANNALS-24-03933 AI is only is good is information that we put into it  https://www.bmj.com/content/389/bmj-2024-082007 You can fast however you want but it is all about the same in the end

GLP1 might cause thyroid cancer in mice but the evidence is drastically lacking in humansOral semaglutide is expensive for an NNT of 50 at 4 yrsTiktok videos of skin care are a scam

https://jamanetwork.com/journals/jama/article-abstract/2834040amiloride is realistically equal to spironolactone for resistant HTNhttps://journals.lww.com/ajg/abstract/2025/05000/higher_rate_of_spontaneous_bacterial_peritonitis.24.aspxprophalaxis antibiotics might not be neededhttps://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2834317If you got a friend in weight loss-- or at least in maintaining weight loss

https://www.jthjournal.org/article/S1538-7836(25)00109-6/fulltextAntithrombotic agents, like aspirin and anticoagulants, are essential for treating many cardiovascular conditions. However, a common side effect is bleeding, with extracranial bleeding—bleeding outside the brain and spinal cord—being quite prevalent. This study, a secondary analysis of the Aspirin in Reducing Events in the Elderly, or ASPREE trial, aimed to explore how clinically significant extracranial bleeding affects the development of functional disability in otherwise healthy older adults.What did the researchers find?Summary of Findings: Incidence of Bleeding: Out of nearly 19,000 participants, about 2.9%, or 547 individuals, experienced clinically significant extracranial bleeding. Functional Independence Impact: Those who experienced such bleeding had a more than two-fold increase in the risk of developing dependence on activities of daily living, or ADLs. Specifically, the hazard ratio for ADL dependence was 2.46, indicating a significant association. Types of Bleeding: Both gastrointestinal (GI) bleeding and other non-GI extracranial bleeding showed similar risks, with hazard ratios of 2.29 and 2.68 respectively. Importantly, these associations held true whether participants were on aspirin or a placebo. Strengths of the Study: Large Sample Size: With nearly 19,000 participants, the study provides robust data. Rigorous Data Collection: Bleeding events were meticulously documented and adjudicated by medical professionals. Comprehensive Analysis: The detailed follow-up and frequent assessments allowed for thorough monitoring of participants' health outcomes over several years. Weaknesses of the Study: Granular Data Absence: Specific details about hospitalization, such as length of stay or the number of transfusions, were not available. Data Collection Frequency: Bleeding events were assessed continuously, whereas ADL dependence was assessed biannually. This discrepancy could lead to challenges in pinpointing the exact onset of functional dependence relative to bleeding events.

https://www.nejm.org/doi/full/10.1056/NEJMoa2405182?query=recirc_Semantic  Key Takeaways Extended Predictive Value of Biomarkers: High-sensitivity C-reactive protein (CRP), LDL cholesterol, and lipoprotein(a) levels were found to be predictive of cardiovascular events over a 30-year period. These markers contribute independently to long-term cardiovascular risk beyond traditional 10-year risk estimates. Study Design and Population: The study enrolled 27,939 initially healthy U.S. women who were followed for 30 years. The primary endpoint was the occurrence of a first major adverse cardiovascular event, including myocardial infarction, coronary revascularization, stroke, or death from cardiovascular causes. Predictive Strength of Biomarkers: Among the biomarkers, high-sensitivity CRP showed the strongest association with future cardiovascular events (hazard ratio for top quintile: 1.70). LDL cholesterol and lipoprotein(a) also significantly predicted risk, albeit to a slightly lower degree (hazard ratios: 1.36 and 1.33, respectively).  NOT STATIN WITH CRP Implications for Clinical Practice: Combining all three biomarkers may offer the best method for identifying high-risk individuals who might benefit from early intervention.   YOU HAVE TO PROSPECTIVELY VALIDATE THIS The study supports extending cardiovascular prevention strategies beyond traditional risk assessments. Lifestyle and pharmacologic interventions should target multiple pathways, including lipid levels and inflammation. Key Limitations Study Population: The study cohort predominantly consisted of female health professionals who are mostly White (94%), which may limit generalizability. The results may not extend to males or more diverse populations without further studies. Absence of Repeated Measures: Biomarkers were measured only at baseline without repeated measures over time. This limits the ability to observe changes in biomarker levels and their association with risk over time. Statin Use Data: Increasing use of statins over the study period was not thoroughly considered in initial analyses, and detailed data on adherence and duration are lacking. Sensitivity analyses attempted to account for this by censoring data at the time of first statin prescription, but residual confounding may be present. Concerns with Study Design Cohort Composition: The study's focus on health professionals might have led to better access to healthcare and healthier lifestyle choices, potentially skewing outcomes. Non-White participants were underrepresented, raising concerns about the applicability of findings to more diverse groups. Single Time Point Measurement:Only baseline biomarker levels were used for long-term prediction, which may not account for variability and changes in risk factors over time.