One-Minute Telegram Archiv

This article contains a collection of content written for the One-Minute Telegram, a biweekly newsletter that presents the newest medical research condensed into just one minute of reading. This newsletter is designed for all of our colleagues who want to stay current on the latest medical literature without having to comb through and dissect medical studies themselves. It is peer-reviewed by our team of physician editors and integrated into the Amboss library. Even after a long night shift or a busy day on the wards, it should go down easy. Sign up via the link in “Tips and Links” below.

See also our One-Minute Telegram Archiv 2022, One-Minute Telegram Archiv 2021 and One-Minute Telegram Archiv 2020.

• One-Minute Telegram 71-2023
  • TRUNCATE-TB: Sometimes less isn’t less
  • Statin your case: high-intensity therapy vs. treat-to-target for elevated LDL-C
  • NOSTONE left unturned
• One-Minute Telegram 70-2023
  • The efficacy of the RSV vaccine is nothing to sneeze at
  • USPSTF reaffirms: Do not screen asymptomatic patients for HSV!
  • Sleep tight and keep your heart right
• One-Minute Telegram 69-2023
  • The jury is still out on the best treatment approach to early sepsis
  • Shed those meds: decreasing polypharmacy by actively deprescribing
  • Does vitamin D prevent diabetes in people with prediabetes?
• One-Minute Telegram 68-2023
  • After orthopedic trauma, two aspirin a day keep fatal blood clots away
  • Loop me in: torsemide or furosemide for heart failure?
  • They tested their poo, but didn’t follow through
• One-Minute Telegram 67-2023
  • Freezing the progression of atrial fibrillation
  • Empagliflozin improves outcomes in chronic kidney disease
  • Fluvoxamine: no panacea for COVID-19
• One-Minute Telegram 66-2023
  • 2021 AHA/ACC model overestimates the risk of coronary artery disease
  • Chlorthalidone and hydrochlorothiazide: not so different after all
  • I would walk 5000 steps, but should I walk 5000 more?

TRUNCATE-TB: Sometimes less isn’t less

One-Minute Telegram 71-2023-1/3

10-second takeaway

The currently recommended treatment regimen for drug-susceptible pulmonary tuberculosis (TB) may lead to overtreatment, nonadherance, and increased drug resistance. In this open-label trial with HIV-negative patients, a two-month bedaquiline-linezolid treatment regimen followed by extended treatment only for persistent or relapsing TB was noninferior to a standard six-month regimen with respect to death, persistent disease, and prolonged treatment. Shorter treatment regimens combined with extended monitoring may prevent overtreatment and reduce the cost of care.

Study breakdown

• Study population: 674 HIV-negative adults aged 18–65 years with symptoms or radiographic evidence of TB and a positive nucleic acid test for TB without rifampin resistance
• Methods
  • International, randomized, phase 2–3 prospective, open-label noninferiority trial
  • Randomization to either of the following:
    • Standard therapy: 8 weeks of isoniazid (H) + rifampin (R) + pyrazinamide (Z) + ethambutol (E) followed by 16 weeks of H + R
    • Shortened therapy: 8-week treatment with one of four different drug combinations followed by monitoring, extended treatment for persistent disease, and/or treatment for relapse
  • Regular monitoring with symptom assessment and sputum smears
  • Primary outcomes: composite of death, ongoing treatment, or active tuberculosis
  • Follow-up: at 96 weeks
• Main results
  • Initial treatment with 8 weeks of H + Z + E + bedaquiline-linezolid was noninferior to standard therapy (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1).
  • Initial treatment with 8 weeks of H + Z + E + linezolid + high-dose R did not meet noninferiority criteria.
  • Recruitment to the remaining two therapy groups was discontinued due to sample size considerations.
  • No difference in adverse events, death, or acquired drug resistance between groups
• Limitations include:
  • Open-label design
  • Exclusion of HIV-positive participants
• Study funding: Singapore National Medical Research Council and others
• Original study: Treatment strategy for rifampin-susceptible tuberculosis ^[1]
• AMBOSS links: Tuberkulose

Statin your case: high-intensity therapy vs. treat-to-target for elevated LDL-C

One-Minute Telegram 71-2023-2/3

10-second takeaway

Statins reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD), but the best strategy for initiating statin therapy remains unclear. In this trial, moderate-intensity statin therapy followed by titration to a targeted LDL-C level was noninferior to high-intensity statin therapy without a targeted LDL-C in reducing the risk for a composite of major cardiovascular events. In patients with CAD, titration of moderate-intensity statin therapy to a target LDL-C goal may be as effective and safe as initiation of treatment with a high-intensity statin.

Study breakdown

• Study population: 4400 adults with clinically diagnosed CAD (mean age 65 years; 72% male)
• Methods
  • Multicenter, open-label, randomized, noninferiority trial
  • Randomization of statin therapy 1:1 to:
    • High-intensity: rosuvastatin 20 mg or atorvastatin 40 mg once daily, no target LDL-C
    • Titrated-intensity: rosuvastatin 10 mg or atorvastatin 20 mg once daily followed by upward or downward titration to target goal LDL-C of 50–70 mg/dL
  • Primary endpoint: composite of all-cause death, myocardial infarction, stroke, or coronary revascularization
  • Follow-up: 3 years
• Main results
  • Titrated-intensity statin therapy was noninferior to high-intensity statin therapy.
    • Primary endpoint: titrated-intensity group 8.1% vs. high-intensity group 8.7% (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points])
    • All-cause death (absolute difference, < 0.1% [95% CI, -0.9% to 0.9%])
    • Myocardial infarction (absolute difference, -0.5% [95% CI, -1.1% to 0.1%])
    • Stroke (absolute difference, -0.5% [95% CI, -1.1% to 0.1%])
• Limitations include:
  • Open-label design
  • Study may have been underpowered, given lower-than-anticipated event rates.
  • The study did not consider the use of statins for primary prevention.
  • The study does not provide evidence on whether treatment-to-target results in improved outcomes, reduced adverse effects, and/or a better cost-benefit ratio compared with high-dose statin therapy.
• Study funding: Samjin Pharmaceutical and Chong Kun Dang Pharmaceutical
• Original study: Treat-to-target or high-intensity statin in patients with coronary artery disease: a randomized clinical trial ^[2]
• AMBOSS links: Atherosklerose | Koronare Herzkrankheit | Dyslipidämien

NOSTONE left unturned

One-Minute Telegram 71-2023-3/3

10-second takeaway

Thiazide diuretics are commonly used to prevent the recurrence of nephrolithiasis, but studies supporting this practice are limited. In this trial with patients in Switzerland with a history of recurrent nephrolithiasis, daily hydrochlorothiazide (HCTZ) did not reduce the incidence of nephrolithiasis recurrence compared to placebo but did cause more hypokalemia, gout, and plasma creatinine elevation. The risks of daily thiazide diuretic use should be weighed against the potential lack of benefit for prevention of recurrent nephrolithiasis.

Study breakdown

• Study population: 416 adults with a history of recurrent calcium-containing kidney stones within 10 years (median age 49 years; 20% female; 99% White)
• Methods
  • Double-blind multicenter randomized clinical trial
  • Randomized 1:1:1:1 to HCTZ 12.5 mg, 25 mg, or 50 mg, or a placebo once daily
  • Primary outcome: a composite of symptomatic or radiologic recurrence of kidney stones
  • Median follow-up: 2.9 years
• Main results
  • Stone recurrence was 59% in the placebo group and did not differ significantly compared to placebo in the HCTZ treatment groups:
    • 12.5 mg HCTZ group: 59% (rate ratio 1.33; 95% CI, 0.92–1.93)
    • 25 mg HCTZ group: 56% (rate ratio, 1.24; 95% CI, 0.86–1.79)
    • 50 mg HCTZ group: 49% (rate ratio, 0.92; 95% CI, 0.63–1.36)
  • Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and plasma creatinine elevation > 150% baseline were more common in participants taking HCTZ than those taking placebo.
  • Nonadherance rate was 26%.
• Limitations include:
  • Underrepresentation of women and people of color
  • Results are not generalizable to the prevention of recurrence after a first episode of nephrolithiasis.
  • Study duration of 3 years limits generalizability to longer treatment periods.
  • High incidence of nonadherance may have introduced bias toward the null hypothesis.
• Study funding: Swiss National Science Foundation; Inselspital, Bern University Hospital
• Original study: Hydrochlorothiazide and prevention of kidney stone recurrence ^[3]
• AMBOSS links: Nephrolithiasis

The efficacy of the RSV vaccine is nothing to sneeze at

One-Minute Telegram 70-2023-1/3

10-second takeaway

Respiratory syncytial virus (RSV) is an important cause of death and disease in older adults, accounting for over 12,000 deaths per year among this population in the US alone. In this large-scale, placebo-controlled phase 3 trial, a single dose of RSV vaccine had an acceptable safety profile and significantly reduced the incidence of RSV infection and RSV-related lower respiratory tract disease in older adults. This RSV vaccine may be a safe and effective method for protecting this population from both mild and severe manifestations of RSV infection.

Study breakdown

• Study population: 24,966 adults, ≥ 60 years of age (mean age 69.5 years; 52% female; 39% with comorbidities)
• Methods
  • Ongoing international, randomized, phase 3 trial
  • Randomized 1:1 to receive a single dose of the RSVPreF3 OA vaccine vs. placebo for one RSV season
  • Primary outcome: vaccine efficacy against RSV-related lower respiratory tract disease
  • Subgroup safety assessment, utilizing solicited and unsolicited reporting of injection site and systemic reactions
  • Median follow-up: 6.7 months
• Main results
  • Vaccine efficacy compared with placebo
    • 82.6% (96.95% CI, 57.9–94.1) for prevention of RT-PCR-confirmed RSV-related lower respiratory tract disease (primary outcome)
    • 94.1% (95% CI, 62.4–99.9) for prevention of severe RSV-related lower respiratory tract disease
    • 71.7% (95% CI, 56.2–82.3) for prevention of RSV-related acute respiratory infection
    • Similar efficacy for RSV A and B subtypes
  • Adverse events associated with the vaccine were transient and of mild to moderate severity.
• Limitations include: small number of participants > 80 years of age
• Study funding: GlaxoSmithKline Biologicals
• Original study: Respiratory syncytial virus prefusion F protein vaccine in older adults ^[4]
• AMBOSS links: Geriatrie | Akute Bronchitis

USPSTF reaffirms: Do not screen asymptomatic patients for HSV!

One-Minute Telegram 70-2023-2/3

10-second takeaway

Serologic testing for herpes simplex virus (HSV) in patients without symptoms of genital herpes has a high false-positive rate, and whether treatment for asymptomatic HSV is warranted is controversial. The United States Preventive Services Task Force (USPSTF) has reaffirmed its recommendation against routine serologic screening for genital HSV in immunocompetent, HIV-negative, asymptomatic adolescents and adults, including pregnant individuals. Medical providers should avoid routine serologic screening for HSV in this population.

Recommendation breakdown

• Recommendation: The USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including pregnant individuals.
• Applicable population: adolescents and adults, including pregnant individuals, without a known medical history, signs, and/or symptoms of genital herpes
• Additional information
  • Routine serologic screening for HSV has a low predictive value and a high rate of false positives in asymptomatic patients.
  • The benefit of antiviral medications in asymptomatic patients with serologic evidence of HSV infection is unclear.
  • This recommendation does not apply to:
    • Individuals with HIV or other immunosuppressive disorders
    • Individuals requesting testing who have signs, symptoms, or a history of genital herpes
• Limitations include:
  • Need for more studies to assess the benefits and risks of screening for and management of genital herpes in asymptomatic individuals
  • Need for more studies to evaluate the potential benefits and risks of HSV screening in populations disproportionately affected by HSV
• Study funding: Agency for Healthcare Research and Quality (AHRQ)
• Original study: Serologic screening for genital herpes infection: US Preventive Services Task Force reaffirmation recommendation statement ^[5]
• AMBOSS links: Herpesvirus-Infektionen | Sexuell übertragbare Infektionen

Sleep tight and keep your heart right

One-Minute Telegram 70-2023-3/3

10-second takeaway

There is a clear correlation between disordered sleep and the development of cardiovascular disease (CVD). In this cross-sectional, community-based evaluation, irregularities in sleep duration and sleep onset timing were associated with subclinical atherosclerosis. Maintaining a regular sleep schedule with consistent sleep duration may be an important lifestyle recommendation for the prevention of CVD.

Study breakdown

• Study population: 2032 US adults between 45 and 84 years of age (mean age 68 years; 53% female; 38% White; 28% Black; 23% Hispanic; 11% Chinese American)
• Methods
  • Cross-sectional evaluation of participants in a longitudinal cohort study of atherosclerosis across six US communities
  • Sleep regularity was assessed with wrist-worn actigraphs and sleep diaries.
  • Standard deviations (SD) of sleep duration and sleep onset timing were determined for each participant.
  • The presence of subclinical CVD was determined using standard testing for:
    • Coronary artery calcium (CAC)
    • Carotid intima-media thickness (cIMT)
    • Carotid plaque
    • Ankle-brachial index (ABI)
• Main results
  • Participants with irregular sleep duration (SD > 120 minutes) had a significantly higher likelihood of elevated CAC (prevalence ratio, 1.33; 95% CI, 1.03–1.71) and abnormal ABI (1.75; 1.03–2.95) than those with regular sleep duration (SD ≤ 60 minutes).
  • Participants with irregular sleep onset timing (SD > 90 minutes) had higher CAC levels (1.39; 1.07–1.82) than those with regular sleep timing (SD ≤ 30 minutes).
• Limitations include: Causality cannot be inferred given the cross-sectional study design.
• Study funding
  • National Heart, Lung, and Blood Institute
  • National Center for Advancing Translational Sciences
• Original study: Sleep irregularity and subclinical markers of cardiovascular disease: the multi-ethnic study of atherosclerosis ^[6]
• AMBOSS links: Atherosklerose und kardiovaskuläre Prävention | Insomnie

The jury is still out on the best treatment approach to early sepsis

One-Minute Telegram 69-2023-1/3

10-second takeaway

The best approach to sepsis management is an area of active inquiry. This randomized trial of a restrictive vs. liberal fluid strategy for early management of sepsis-induced hypotension showed no difference in in-hospital mortality between the two groups. Whether these findings will affect current sepsis management guidelines remains to be seen.

Study breakdown

• Study population: 1563 adults < 4 hours after initial diagnosis of sepsis-induced hypotension refractory to initial resuscitation (1000–3000 mL of IV crystalloid fluid)
• Methods: multicenter, randomized, nonblinded superiority trial
  • Randomized 1:1 to restrictive fluid strategy (prioritizing early vasopressor use with rescue fluids permitted) vs. liberal fluid strategy (prioritizing early fluid boluses with rescue vasopressors permitted) for 24 hours
  • Primary outcome: all-cause mortality prior to discharge by day 90
• Main results
  • Patients in the restrictive fluid strategy group received an average of 2100 mL less IV fluid (3300 mL vs. 5400 mL) and were significantly more likely to receive vasopressors than the liberal fluid strategy group (59% vs. 37%).
  • No significant difference in mortality before discharge by day 90: 14.0% in the restrictive fluid strategy group; 14.9% in the liberal fluid strategy group (est. mean difference, -0.9%; 95% CI, -4.4 to 2.6)
  • No significant differences in invasive mechanical ventilation, onset of ARDS within the first week of treatment, initiation of renal replacement therapy, or severe adverse events
• Limitations include:
  • Results may not be generalizable to patients with volume overload or volume depletion on presentation, who were excluded from the study population, or to patients who develop sepsis in the hospital, since most participants were enrolled in the emergency department.
  • Trial may not have been powered to detect differences in outcomes among patient subgroups (e.g., patients with CHF and/or kidney disease)

• AMBOSS links: Sepsis | Flüssigkeits- und Volumentherapie
• Original study: Early restrictive or liberal fluid management for sepsis-induced hypotension ^[7]
• Authors: The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network
• Journal: N Engl J Med
• Study funding: NHLBI of the National Institutes of Health

Shed those meds: decreasing polypharmacy by actively deprescribing

One-Minute Telegram 69-2023-2/3

10-second takeaway

Polypharmacy, with its associated costs and adverse effects, is a growing concern among older adults that is often exacerbated by additional prescriptions upon hospital discharge. In this randomized clinical trial, hospitalized patients assigned to a deprescription intervention upon discharge to a post acute care (PAC) facility were prescribed significantly fewer medications at PAC facility discharge and at 90-day follow-up than patients receiving usual care. To reduce polypharmacy in older adults, hospital providers should consider introducing deprescription interventions before discharge.

Study breakdown

• Study population: 372 adults over 50 years of age (mean age 76 years, 62% women) taking at least five prehospital medications (median number 16) and being discharged from the hospital to a PAC facility
• Methods: randomized clinical trial
  • Randomized 1:1 to receive the “Shed-MEDS intervention” (comprehensive medication review prompting deprescribing recommendations implemented with patient approval and continued throughout PAC facility stay) vs. usual care
  • Follow-up at PAC facility discharge and 90 days post-PAC discharge
• Main results: Compared to usual care the intervention group had
  • 14% fewer medications at PAC facility discharge (mean ratio, 0.86; 95% CI, 0.80–0.93) and 15% fewer medications 90 days post-PAC discharge (0.85; 0.78–0.92)
  • Significantly lower medication dosages as measured by the Drug Burden Index
  • Reduced exposure to potentially inappropriate medications
  • Similar rates of adverse drug events
• Limitations include:
  • Potentially limited generalizability, as patients were enrolled at a single academic medical center
  • By increasing awareness of polypharmacy, the study may have also led to avoidance of overprescribing for the nonintervention group, thus limiting the observed intervention effect.

• AMBOSS link: Geriatrie
• Original study: Deprescribing medications among older adults from end of hospitalization through postacute care: a Shed-MEDS randomized clinical trial ^[8]
• Authors: Vasilevskis EE, Shah AS, Hollingsworth EK, et al.
• Journal: JAMA Intern Med
• Study funding: National Institute on Aging of the National Institutes of Health

Does vitamin D prevent diabetes in people with prediabetes?

One-Minute Telegram 69-2023-3/3

10-second takeaway

Factors associated with the prevention of type 2 diabetes in individuals at risk are an area of active research. In this systematic review and metaanalysis of three randomized trials, patients with prediabetes who received oral vitamin D therapy had a moderately reduced risk of developing diabetes compared to those who received placebo. Oral vitamin D therapy may be a safe and effective adjunct to other measures for the prevention of diabetes in patients with prediabetes.

Study breakdown

• Study population: 4190 adults (mean age 61 years, 44% women, 51% White, 33% Asian, 15% Black) with prediabetes
• Methods: systematic review and individual participant data metaanalysis from three randomized clinical trials
  • Randomized 1:1 to receive oral vitamin D (cholecalciferol 20,000 IU weekly, cholecalciferol 4000 IU daily, or eldecalcitol 0.75 mcg daily) vs. placebo
  • Primary outcome: time to onset of diabetes
  • Median follow-up: 3 years
• Main results: Compared to patients receiving placebo, patients in the vitamin D group had
  • Lower rates of developing diabetes (22.7% vs. 25%; adjusted HR, 0.85; 95% CI, 0.75–0.96)
  • Higher rates of normalization of glucose regulation (14.4% vs. 11.1%; rate ratio, 1.30; 1.16–1.46)
  • Similar rates of adverse events (kidney stones, hypercalcemia, hypercalciuria) and death
• Limitations include:
  • Results are not generalizable to populations without prediabetes or other dosages of vitamin D replacement.

• AMBOSS links: Diabetes mellitus
• Original study: Vitamin D and risk for type 2 diabetes in people with prediabetes ^[9]
• Authors: Pittas AG, Kawahara T, Jorde R, et al.
• Journal: Ann Intern Med
• Study funding: None

After orthopedic trauma, two aspirin a day keep fatal blood clots away

One-Minute Telegram 68-2023-1/3

• Background: Low molecular weight heparin (LMWH) is recommended for thromboprophylaxis in patients with fractures. This trial set out to determine if aspirin is noninferior to LMWH as thromboprophylaxis after a fracture.
• Study population: 12,211 adults (median age 44 years, 62% male) with any pelvic, acetabular, and/or surgically repaired extremity fracture
• Methods
  • Pragmatic, multicenter, randomized noninferiority trial
  • Randomized 1:1 to aspirin 81 mg twice daily or LMWH 30 mg twice daily
  • Duration of therapy followed local protocol.
• Main results
  • Mortality was similar between aspirin (0.78%) and LMWH (0.73%) groups (96.2% CI, -0.27 to 0.38).
  • Incidence of pulmonary embolism was the same in both groups (1.49%).
  • Deep vein thrombosis occurred more frequently in the aspirin group than in the LMWH group (2.51% vs. 1.71%; 95% CI, 0.28–1.31).
  • Safety outcomes: Incidence of bleeding complications and other serious adverse events was similar between groups.
• Limitations include:
  • Open-label design may have introduced surveillance bias.
  • Variations in the duration of thromboprophylaxis may have influenced outcomes.
  • Generalizability to other patient groups is limited.

The take-home message?

In this large, open-label trial, aspirin was noninferior to LMWH as thromboprophylaxis after a fracture. Aspirin may be a well-tolerated, effective, inexpensive, and convenient alternative to LMWH following orthopedic trauma.

• AMBOSS links: Tiefe Beinvenenthrombose | Lungenarterienembolie
• Original study: Aspirin or low-molecular-weight heparin for thromboprophylaxis after a fracture ^[10]
• Authors: Major Extremity Trauma Research Consortium
• Journal: N Engl J Med
• Study funding: Patient-Centered Outcomes Research Institute

Loop me in: torsemide or furosemide for heart failure?

One-Minute Telegram 68-2023-2/3

• Background: Loop diuretics are a cornerstone in the management of heart failure, and torsemide may be more effective than other diuretics because of its high bioavailability and long half-life. This study set out to determine if torsemide is more effective than furosemide for reducing mortality in patients hospitalized for acute heart failure.
• Study population: 2859 patients (median age 65 years, 36.9% female) hospitalized for de novo heart failure or worsened chronic heart failure
• Methods
  • Open-label, pragmatic, randomized comparative-effectiveness study
  • Randomized 1:1 to torsemide or furosemide on discharge
  • Dosage was clinician-determined (recommended drug equivalency was 1 mg torsemide to 2–4 mg furosemide).
  • Recruitment ended upon reaching a predetermined number of all-cause deaths (median follow-up was 17.4 months).
• Main results
  • No difference in all-cause mortality: 26.1% in the torsemide group, 26.2% in the furosemide group (HR, 1.02; 95% CI, 0.89–1.18)
  • No difference in total hospitalizations: 940 in the torsemide group, 987 in the furosemide group (RR, 0.94; 0.84–1.07)
  • Mean furosemide equivalent diuretic doses were similar at discharge in both groups: 79.1 mg in the furosemide group, 79.5 mg in the torsemide group
  • Crossover occurred in 5.4%; nonadherence at 6 months was 9.5%.
• Limitations include:
  • Early attainment of the predetermined study endpoint resulted in a smaller-than-anticipated sample size, which limited subgroup analyses and assessments of subtle benefits and harms.
  • All-cause mortality may have been too broad an outcome to detect subtle differences between drugs.
  • High crossover and nonadherence rates may have introduced bias toward neutral results.

The take-home message?

In this large open-label randomized clinical trial, the use of torsemide vs. furosemide following hospitalization for heart failure did not result in a significant difference in all-cause mortality at 12 months. These results suggest that the pharmacokinetic advantages of torsemide may not be clinically significant, but study limitations necessitate cautious interpretation.

• AMBOSS links: Dekompensierte Herzinsuffizienz
• Original study: Effect of torsemide vs furosemide after discharge on all-cause mortality in patients hospitalized with heart failure: the TRANSFORM-HF randomized clinical trial ^[11]
• Authors: Mentz RJ, Anstrom KJ, Eisenstein EL et al.
• Journal: JAMA
• Study funding: National Institutes of Health

They tested their poo, but didn’t follow through

One-Minute Telegram 68-2023-3/3

• Background: Colonoscopy is recommended after a positive stool-based test (SBT) for colorectal cancer (CRC) screening. This study investigated the rates of and factors associated with follow-up colonoscopy (FU-CY) after a positive SBT.
• Study population: 32,769 primary care patients aged 50–70 years with an average risk of CRC and a positive SBT
• Methods: retrospective analysis of anonymized electronic health records
• Main results
  • FU-CY was performed within 360 days of a positive SBT in 56.1% of patients.
  • White patients were more likely to have FU-CY than Black patients (HR, 0.85; 95% CI, 0.80–0.91) or Asian patients (0.79; 0.69–0.91).
  • Individuals with commercial insurance were more likely to have FU-CY than those with Medicare (0.95; 0.91–0.99) or Medicaid (0.79; 0.73–0.85).
  • Patients tested with multitarget stool DNA tests were more likely to have FU-CY than those who had a fecal immunochemical test (1.63; 1.57–1.68).
  • FU-CY rates were lower in 2020 than in 2019, which the authors attribute to the COVID-19 pandemic.
• Limitations include:
  • Analysis of electronic health records data may have led to confounding.
  • Generalizability to other populations is limited.

The take-home message?

In this large retrospective study, FU-CY occurred less frequently than recommended, especially among Black and Asian patients, those with noncommercial insurance, and those who had a fecal immunochemical test. Physicians screening for CRC should be aware of this potential gap in care to help prevent complications and mortality related to delayed diagnosis and treatment of CRC.

• AMBOSS links: Kolorektales Karzinom | Kolonpolypen
• Original study: Rates of follow-up colonoscopy after a positive stool-based screening test result for colorectal cancer among health care organizations in the US, 2017-2020 ^[12]
• Authors: Mohl JT, Ciemins EL, Miller-Wilson L et al.
• Journal: JAMA Netw Open
• Study funding: Exact Sciences Corporation

Freezing the progression of atrial fibrillation

One-Minute Telegram 67-2023-1/3

• Background: Paroxysmal atrial fibrillation (AF) frequently progresses to persistent AF, ^[13] which is associated with higher rates of thromboembolism, heart failure, and health care utilization. Early cryoablation therapy reduces the recurrence of atrial tachyarrhythmias within the first year of treatment compared to antiarrhythmic drug therapy. ^[14] This follow-up analysis set out to determine whether early cryoablation has longer-term disease-modifying benefits.
• Study population: 303 patients with untreated paroxysmal AF
• Methods: multicenter, open-label randomized trial
  • Rhythm control therapy with cryoballoon ablation (n = 154) or antiarrhythmic drug therapy (n = 149)
  • Cardiac events were recorded using implantable loop recorders.
  • Follow-up: 3 years
• Main results (intention-to-treat analysis)
  • Episodes of persistent AF (lasting > 7 days or lasting > 48 hours and requiring cardioversion)
    • Ablation group: 1.9%
    • Antiarrhythmic drug group: 7.4%
    • HR, 0.25; 95% CI, 0.09–0.70
  • Recurrent atrial tachyarrhythmia (lasting ≥ 30 seconds)
    • Ablation group: 56.5%
    • Antiarrhythmic drug group: 77.2%
    • HR, 0.51; 0.38–0.67
  • Hospitalization
    • Ablation group: 5.2%
    • Antiarrhythmic drug group: 16.8%
    • Relative risk, 0.31; 0.14–0.66
  • Trend toward lower risk of serious adverse events in the ablation group (RR, 0.45; 0.19–1.05)
• Limitations include:
  • 18 patients crossed over to the ablation group after unsuccessful medical therapy.
  • Outcomes may not be generalizable to other ablation techniques.

The take-home message?

Over a 3-year follow-up, patients with paroxysmal AF treated with early cryoballoon ablation had lower rates of progression to persistent AF, recurrent atrial tachyarrhythmia, and hospitalization compared to patients treated with antiarrhythmic drug therapy. Larger trials are required to assess whether cryoballoon ablation can also reduce rates of stroke, heart failure, and death in this patient population.

• AMBOSS links: Vorhofflimmern
• Original study: Progression of atrial fibrillation after cryoablation or drug therapy ^[15]
• Authors: Andrade JG et al.
• Journal: NEJM
• Study funding: Cardiac Arrhythmia Network of Canada and others

Empagliflozin improves outcomes in chronic kidney disease

One-Minute Telegram 67-2023-2/3

• Background: SGLT2 inhibitors reduce the risk of chronic kidney disease (CKD) progression in patients with proteinuric CKD and type 2 diabetes. ^[16][17] This study set out to assess the effects of empagliflozin on a diverse group of patients with CKD, including those without diabetes or proteinuria.
• Study population: 6609 adults with CKD (mean age 63.8 years; 33.2% women; 54% without diabetes) with an estimated glomerular filtration rate (eGFR) of 20–45 mL/min/1.73 m², regardless of albuminuria, or an eGFR of 45–90 mL/min/1.73 m² and a urinary albumin:creatinine ratio ≥ 200 mg/g
• Methods: double-blind randomized controlled trial
  • Empagliflozin 10 mg or placebo once daily
  • Median follow-up: 2 years
• Main results
  • Primary outcome: progression of CKD or death from cardiovascular causes
    • Empagliflozin group: 13.1%
    • Placebo group: 16.9%
    • HR, 0.72; 95% CI, 0.64–0.82
    • No significant differences across eGFR subgroups nor between patients with or without diabetes
  • Secondary outcomes
    • Lower rate of hospitalization in the empagliflozin group (HR, 0.86; 0.78–0.95)
    • No difference in all-cause mortality or composite of heart failure hospitalizations and cardiovascular death
  • Similar rates of serious adverse events between groups
• Limitations include: A low number of cardiovascular events may have reduced the statistical power for the assessment of secondary outcomes.

The take-home message?

Patients with CKD treated with empagliflozin had lower rates of CKD progression or cardiovascular mortality than those who received placebo, regardless of diabetes status or eGFR subgroup.

• AMBOSS links: Chronische Nierenerkrankung | SGLT2-Inhibitoren
• Original study: Empagliflozin in patients with chronic kidney disease ^[18]
• Authors: The EMPA-KIDNEY Collaborative Group
• Journal: N Engl J Med
• Study funding: Boehringer Ingelheim and others

Fluvoxamine: no panacea for COVID-19

One-Minute Telegram 67-2023-3/3

• Background: A recent metaanalysis suggests that fluvoxamine, a selective serotonin reuptake inhibitor with antiinflammatory effects, can reduce COVID-19-related hospitalizations. ^[19][20] However, high-quality randomized studies demonstrating a benefit with fluvoxamine for the treatment of COVID-19 have so far been lacking.
• Study population: 1288 patients ≥ 30 years of age (mean age 47 years; 57% female) with mild-to-moderate COVID-19 with > 2 symptoms for < 7 days
• Methods: randomized controlled adaptive platform trial ^[21]
  • Fluvoxamine (50 mg; n = 674) or placebo (n = 614) twice daily for 10 days
  • Follow-up: 28 days
• Main results
  • Primary outcome: median time to recovery (3 consecutive symptom-free days)
    • Fluvoxamine group: 12 days (IQR, 11–14 days)
    • Placebo group: 13 days (IQR, 12–13 days)
    • HR, 0.96; 95% credible interval, 0.86–1.06
  • Secondary outcome: composite of hospitalization, urgent care or ED visit, or death
    • Fluvoxamine group: 3.8%
    • Placebo group: 3.9%
    • HR, 1.1; 0.5–1.8
  • Similar rates of adverse events and duration of symptoms in both groups
• Limitations include:
  • Study likely underpowered to detect a difference in secondary outcome because of the low number of clinical events in both groups
  • Significant delay from symptom onset to treatment initiation (median: 5 days)

The take-home message?

In this RCT, fluvoxamine did not improve clinical outcomes in patients with mild-to-moderate COVID-19 compared to placebo.

• AMBOSS links: COVID-19
• Original study: Effect of fluvoxamine vs placebo on time to sustained recovery in outpatients with mild to moderate COVID-19: a randomized clinical trial ^[22]
• Authors: McCarthy MW et al.
• Journal: JAMA
• Study funding: National Center for Advancing Translational Sciences

2021 AHA/ACC model overestimates the risk of coronary artery disease

One-Minute Telegram 66-2023-1/3

• Background: Pretest probability (PTP) models for obstructive coronary artery disease (CAD) include the European Society of Cardiology PTP (ESC-PTP) model, risk factor-weighted clinical likelihood (RF-CL) model, and the 2021 American Heart Association/American College of Cardiology PTP (AHA/ACC-PTP) model. ^[23][24][25] The aim of this study was to determine whether PTP models that categorize chest pain (ESC-PTP and RF-CL) and/or include additional risk factors (RF-CL) are more accurate than the AHA/ACC-PTP.
• Study population: 50,561 patients (mean age 57.3 years, 54% female) with symptoms suggestive of obstructive CAD, without previously diagnosed CAD, receiving first-time coronary computed tomography angiography (CCTA)
• Methods: multicenter cohort study between 2008 and 2019
  • Invasive coronary angiography (ICA) was performed based on CCTA results and standard clinical practice.
  • Prevalence of obstructive CAD was determined using ICA.
  • AHA/ACC-PTP, ESC-PTP, and RF-CL were calculated and compared.
• Main results
  • Obstructive CAD prevalence: 8.0%
  • Median predicted prevalence of obstructive CAD
    • AHA/ACC-PTP: 16% (95% CI, 13–32%)
    • ESC-PTP: 11% (6–19%)
    • RF-CL: 5% (2–11%)
  • RF-CL had the highest accuracy (P < 0.001)
  • AHA/ACC-PTP had lower accuracy in predicting prevalence of CAD than ESC-PTP (P < 0.001).
  • AHA/ACC-PTP model overestimated the prevalence of CAD by a factor of 2.6 (2.6–2.7); overestimation was highest (factor of 4.8) in patients with nonanginal pain.
• Limitations include:
  • Limited generalizability of results
    • Patients in the database used were predominantly White.
    • Patients with severe kidney disease and arrhythmias or severe obesity were not included.
  • Risk of selection bias: All participants had been referred for CTA, which excluded very low-risk patients.

The take-home message?

The AHA/ACC-PTP model significantly overestimated the prevalence of obstructive CAD. Models that include risk factors for CAD and symptom characteristics have the highest accuracy and may reduce unnecessary testing in patients with a low PTP of obstructive CAD. Care should be taken in generalizing these results to populations not included in this study.

• AMBOSS links: Akutes Koronarsyndrom | Koronare Herzkrankheit
• Original study: Performance of the American Heart Association/American College of Cardiology guideline-recommended pretest probability model for the diagnosis of obstructive coronary artery disease ^[26]
• Authors: Winther S et al.
• Journal: JAHA
• Study funding: Novo Nordisk Foundation

Chlorthalidone and hydrochlorothiazide: not so different after all

One-Minute Telegram 66-2023-2/3:

• Background: Chlorthalidone (CTD) is the preferred thiazide diuretic antihypertensive according to the 2017 ACC/AHA hypertension guidelines, ^[27] but recent research has shown that hydrochlorothiazide (HCTZ) may have similar efficacy to CTD in preventing cardiovascular disease (CVD) events, with a lower risk of adverse events. ^[28] This study compared the effect of CTD vs. HCTZ on the risk of major CVD events.
• Study population: 13,523 adults in the Veterans Affairs Healthcare System ≥ 65 years of age receiving HCTZ for hypertension (mean age 72 years, 97% male, 15% Black)
• Methods: multicenter, pragmatic, open-label trial (median follow-up 2.4 years)
  • Patients were randomized to either remain on HCTZ (25 mg or 50 mg) or switch to CTD (12.5 mg or 25 mg).
  • Primary outcome: composite of non-cancer-related deaths and nonfatal CVD events, e.g., myocardial infarction (MI) or stroke
  • Secondary outcomes: individual components of primary outcome
  • Safety outcomes include electrolyte abnormalities, hospitalization, and acute kidney injury.
• Main results
  • No between-group differences in primary outcome (HR, 1.04; 95% CI, 0.94–1.16) or secondary outcomes
  • Hypokalemia: 6.0% in the CTD group, 4.4% in the HCTZ group (HR, 1.38; 1.19–1.60)
  • Subgroup analyses
    • Incidence of the primary outcome was lower with CTD than with HCTZ in patients with previous MI and/or stroke (14.3% vs. 19.4%).
    • Incidence of the primary outcome was higher with CTD than with HCTZ in patients without previous MI or stroke (9.9% vs. 8.9%).
• Limitations include:
  • Open-label design may have influenced adherence and testing frequency.
  • Results may not be applicable to higher doses of CTD or HCTZ.
  • Generalizability: Study population was 97% male.

The take-home message?

Patients with hypertension receiving HCTZ had a similar risk of CVD events and non-cancer-related death compared to patients receiving CTD at 2.4 years follow-up. Care should be taken in generalizing these results to higher medication doses and patients with a history of a major CVD event.

• AMBOSS links: Arterielle Hypertonie | Akutes Koronarsyndrom | Koronare Herzkrankheit
• Original study: Chlorthalidone vs. hydrochlorothiazide for hypertension–cardiovascular events ^[29]
• Authors: Ishani A et al.
• Journal: NEJM
• Study funding: Veterans Affairs Cooperative Studies Program

I would walk 5000 steps, but should I walk 5000 more?

One-Minute Telegram 66-2023-3/3:

• Background: The oft-cited recommendation to take 10,000 steps/day originated as a marketing campaign, not from the scientific literature. The aim of this trial was to assess whether daily step count is associated with the risk of cardiovascular disease (CVD) events.
• Study population: 20,152 adults ≥ 18 years of age (mean age 63 years, 52% female, > 70% non-Hispanic White)
• Methods: metaanalysis of 8 prospective studies (mean follow-up 6.2 years)
  • Study requirements: device-measured steps and follow-up for CVD events
  • Step volume: average steps per day over a single 3–7-day period
  • Primary outcome: first subsequent CVD event (stroke, coronary artery disease, heart failure) stratified by sex and age
• Main results
  • In participants ≥ 60 years of age, 6000–9000 steps/day was associated with an approx. 50% lower risk of CVD events compared to 2000 steps/day (HR, 0.51; 95% CI, 0.41–0.63).
  • In adults < 60 years of age, steps/day was not associated with risk of CVD events.
  • There were no subgroup differences in risk of CVD events by sex.
• Limitations include:
  • Potential for residual confounding and reverse causality
  • Follow-up period may not have been long enough to capture benefits of higher steps/day in young adults.

The take-home message?

Higher steps/day were associated with a lower risk of CVD events than lower steps/day in adults ≥ 60 years of age. Benefits also began with step counts well below the widely promoted 10,000 steps/day.

• AMBOSS links: Atherosklerose und kardiovaskuläre Prävention
• Original study: Prospective association of daily steps with cardiovascular disease: a harmonized meta-analysis ^[30]
• Authors: Paluch AE et al.
• Journal: Circulation
• Study funding: Centers for Disease Control and Prevention