Questioning Medicine

Today, we're discussing two groundbreaking studies from 2024 that challenge our understanding of β-blocker therapy for secondary prevention after myocardial infarction, or MI.Let's start with a Swedish study Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction | New England Journal of Medicine that included over 5,000 patients with normal left ventricular ejection fraction after an MI5. The researchers compared long-term beta-blocker therapy with no beta-blocker treatment. Surprisingly, after 3.5 years, there was no significant difference in the primary endpoint of all-cause death or recurrent MI between the two groups5. This suggests that for patients with preserved heart function after an MI, long-term beta-blocker use may not provide additional benefits.  Now, let's turn to a French study involving 3,700 patients who were already on β-blockers following an MI Beta-Blocker Interruption or Continuation after Myocardial Infarction | New England Journal of Medicine7. This trial compared continuing β-blocker therapy to stopping it. After three years, the results showed a slightly higher incidence of adverse events in the group that stopped β-blockers, primarily due to more hospitalizations for cardiovascular reasons7.What do these studies tell us? Well, they suggest that the benefits of β-blockers might be more modest in our current era of advanced revascularization techniques and modern medical therapies for post-MI patients8. However, it's crucial to note that the Swedish study focused on low-risk patients with normal heart function and they say well there was a lower event rate than expected!!! That is EXPECTED WHEN THE OTHER MEDICATIONS WORK!!! ,8.It's important to remember that these findings don't necessarily apply to all post-MI patients. Those with reduced heart function or other specific indications may still benefit significantly from β-blocker therapy7.In conclusion, while these studies provide valuable insights, there are other trials currently being done to help us better answer this question of what to do with the betablocker post mi

Methods Monday  --- Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials: A Systematic Review | Cardiology | JAMA Network Open | JAMA Network  During the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size is a key component to calculating the sample size. Overly optimistic estimation of event rates and effect sizes may lead to underpowered trials. If you expect 1 event per 100 people and you are looking for 5 events then you only need to enroll….. 500 people but if the actual event rate is 1 per 200 people then in order to get 5 events you need to enroll 1000 people!! You can see enrolling 500 people instead of 1000 would underpower your trial  This article, published in JAMA Network Open in April 2024, presents a systematic review of 344 contemporary cardiovascular randomized clinical trials (RCTs) to evaluate the accuracy of estimated event rates and effect sizes1. The key findings are:Event rates were frequently overestimated: Median observed event rate: 9.0% (IQR, 4.3%-21.4%) Median estimated event rate: 11.0% (IQR, 6.0%-25.0%) 61.1% of trials overestimated the event rate 1Effect sizes were often overestimated: Median observed effect size: 0.91 (IQR, 0.74-0.99) Median estimated effect size: 0.72 (IQR, 0.60-0.80) 82.1% of trials overestimated the effect size The drug companies think their drug is way better than it is or observed to be in trials1Device trials were independently associated with decreased accuracy of event rate estimation compared to drug trials1.The study concludes that the frequent overestimation of event rates and effect sizes in cardiovascular RCTs may contribute to underpowered trials and the inability to adequately test trial hypotheses1. This finding has implications for trial design—if we are not accurate or realistic about the interventions we are likely to underpower the study which means you have to do the whole thing all over again or likely all over again and risk FDA rejecting you drug.

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2821168A team of researchers set out to change that by developing a comprehensive algorithm.The process involved a multidisciplinary panel of 11 expertss with extensive experience in managing urinary retention. These experts evaluated about 100 clinical scenarios to create an initial flow sheet. The algorithm was then refined through interviews with 33 frontline clinicians from various specialties.So, what does this new algorithm recommend? Let's break it down:First, bladder scanning is the preferred method for evaluating patients with urinary retention symptoms. It's also recommended for asymptomatic patients who haven't voided in 3 hours.If a bladder scanner isn't available, the algorithm suggests using either an intermittent straight catheter (ISC) or an indwelling urinary catheter (IUC), with a preference for ISC initially.Now, let's talk about when to catheterize based on bladder scanner volumes. For symptomatic patients, catheterization is recommended when the volume is 300 mL or more. For asymptomatic patients, the threshold is higher at 500 mL or more.Lastly, the algorithm provides guidance on when to transition from intermittent to indwelling catheterization. If a patient needs an ISC more frequently than every 4 hours, or if their output is 500 mL or more every 4 hours, it's appropriate to switch to an IUC

https://jamanetwork.com/journals/jama/article-abstract/2822097Design, Setting, and Participants  Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not.Exposure  Various classes of oral antibiotics.Main Outcomes and Measures  Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group.Results  During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital.Conclusion and Relevance  Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate.

https://www.nejm.org/doi/full/10.1056/NEJMoa2407001ConclusionsNo participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74)

Allaudeen N et al. Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study. J Hosp Med 2024 Dec; 19:1122. (https://doi.org/10.1002/jhm.13458)   Hospital admission for alcohol withdrawal is a problem when it comes to readmission. They just come back--- In this retrospective study of ≈600 patients (96% men) admitted for alcohol withdrawal at 19 Veterans Affairs hospitals during 1 year (2018–2019), researchers evaluated prescription rates of medications for alcohol use disorder (AUD; e.g., naltrexone, acamprosate, disulfiram, gabapentin, topiramate) and scheduled follow-up appointments.The objective of this study was to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence.Neither prescription of AUD agents (to 51% of patients) at hospital discharge nor scheduled follow-up appointments at discharge were associated with 30-day readmissions or 6-month alcohol abstinence.Only direct discharge to residential AUD treatment programs was associated significantly with fewer readmissions (odds ratio, 0.4) and alcohol abstinence (OR, 2.5). Additionally, being discharged with a primary care appointment and actually attending the appointment was associated with fewer hospital readmissions (OR, 0.3).

Real‐world use of glucocorticoids and clinical outcomes in adults hospitalized with community‐acquired pneumonia on medical wards - Malecki - 2024 - Journal of Hospital Medicine - Wiley Online Library This was a retrospective cohort study of 11,500 patients with CAP who were admitted to general medicine units in 7 Canadian hospitals, researchers compared outcomes for patients who received systemic corticosteroids. Patients were excluded if they were admitted to the intensive care units or had COPD or COVID-19 infection. Between those that got steroids and those that didn’t get steroids there was no differences in intensive care admissions, hospital length of stay, or 30-day readmissions. HOWEVER, In an adjusted analysis, patients who received systemic corticosteroids were significantly more likely to die in the hospital than were patients who didn't receive steroids (8.0% vs. 6.3%; P=0.03).  LET’S BE CLEAR THIS IS FOR NON-SEVERE PNA!! If you have severe pna and are going to the ICU then the evidence and guidelines clearly indicate steroids are appropriate. Critical Care Medicine (lww.com) 

2024 ESC guidelines propose a simple new BP categorization: Non-elevated: less than 120/70 mm Hg in the office (pharmacological treatment is not recommended). Elevated: 120 to 139/70 to 89 mm Hg (pharmacological treatment is recommended for some, depending on cardiovascular disease [CVD] risk and follow-up BP measurements). Hypertension: 140/90 mm Hg or greater (confirmation and prompt pharmacological treatment is recommended).     lifestyle interventions are particularly critical for individuals with an elevated BP but a low predicted risk of CVD. Adults in this group are common and account for up to one-third of all CVD events,  2024 ESC Guidelines provide two major new lifestyle approaches for managing elevated BP and hypertension.  first new option is potassium supplementation, either by dietary supplementation or potassium-enriched salt substitutes. The mechanistic and observational data supporting the benefits of potassium supplementation on BP are not new. However, recent CVD outcomes trials demonstrate the benefits of potassium supplementation where clinically appropriate.  Potassium-enriched salts typically contain 75% sodium chloride and 25% potassium chloride, while dietary potassium sources include foods such as bananas (450 mg per medium-sized banana), unsalted boiled spinach (840 mg per cup), and mashed avocado (710 mg per cup)  The second new option is to increasingly understand the BP-lowering benefits of resistance exercise training.4 Not everyone can perform the aerobic exercises traditionally recommended in BP management guidelines, and resistance exercise offers an important alternative for both clinicians and patients.  ANY EXERCISE 

Question  Does adding centralized mailed fecal immunochemical testing and patient navigation to usual care improve colorectal cancer (CRC) screening in US federally qualified health centers? pragmatic randomized clinical trial was conducted Patients were enrolled and randomly assigned to usual care alone (control group) or intervention (2,001 participants per group). Intervention participants received mailed screening outreach materials including an introductory letter, FIT kit packet with instructions and return postage, and two reminder letters if necessary, in addition to usual care. Navigation to facilitate follow-up colonoscopy was offered to intervention participants with positive results of mailed FIT. The researchers found that intervention participants were THREE TIMES more likely than controls to complete screening within six months of randomization (30.0 versus 9.7 percent). Overall, positive FIT results in the intervention arm completed follow-up colonoscopy within six months more often than those in the control arm. This means more colonoscopies which SHOULD mean more cancer Advanced colorectal neoplasia defined as advanced adenoma or CRC.was detected in 1.4 and 0.7 percent of intervention and control participants, respectively. Make it easy for people—we are in an era of EASY. Lets make medicine easy

Packer M et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2024 Nov 16; [e-pub].https://doi.org/10.1056/NEJMoa2410027  In the industry-funded SUMMIT trial (NCT04847557), investigators examined cardiovascular outcomes of tirzepatide — an agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors — over a longer period in patients with HFpEF and obesity.  The 731 study participants had elevated filling pressures or an elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and a heart failure exacerbation event within the prior 12 months or a decreased estimated glomerular filtration rate <70 mL/min/1.73 m2. They were randomized to once-weekly subcutaneous tirzepatide (up to 15 mg) or placebo for at least 52 weeks with a median follow-up of 104 weeks.Compared with placebo, tirzepatide resulted in significantly fewer primary-endpoint events (adjudicated heart-failure worsening or cardiovascular death) — 10% vs. 15% (hazard ratio, 0.62) — HOWEVER--Death from any cause WAS NO DIFFERENT! (hazard ratio, 1.25; 95% CI, 0.63 to 2.45) (Table 2 and Fig. S4). ALSO-- Adjudicated worsening heart-failure event resulting in hospitalization, intravenous drugs in an urgent care setting, or intensification of oral diuretic therapy is great but not what we care about If I just have to increase your oral meds is that really worsening heart failure or you just eating too much on thanksgiving day??? What do we care about here— Hospitalizations—and worsening heart-failure event resulting in hospitalization —was 3.3% in tirzepitide and 7.1% in the control group. Which is a difference of 4 percent and a NNT of 25 to prevent hospitalizatoins  The other primary endpoint was…Kansas city cardio questionnaireand significantly greater improvement (by approximately 7 points) in the Kansas City Cardiovascular Questionnaire clinical summary score (assessed at 52 weeks).  Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care: JACC State-of-the-Art Review | Journal of the American College of Cardiology   As will be developed further, a change of 5 points is considered to be a small but clinically important change, whereas changes of 10 and 20 points are considered moderate-to-large and large-to-very large clinical changes.  On good RX – a two year script of terzep 15mg that was used in this study would cost around – 24,000 or roughly 1000$ per month. That means we have to spend 2.4 million dollars to prevent 4 hospitalistzations from heart failure at 2 yrs!