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An open prescription bottle of Hydroxychloroquine 200 MG with pills spilling from it

Hydroxychloroquine and the risk for incident retinopathy

Patients with systemic lupus erythematosus and other inflammatory conditions are often prescribed medications such as hydroxychloroquine to address joint pain, rashes, lupus flares, and fatigue. However, retinopathy has been observed in some patients taking hydroxychloroquine for long periods, and screening is recommended by the American Society of Opthalmology after 5 years of treatment.

A nationwide group of researchers led by April M. Jorge, MD, of Harvard Medical School and Ronald B. Melles, MD, of Kaiser Permanente Northern California conducted a cohort study to characterize the long-term risk for incident hydroxychloroquine retinopathy and how accurately the average hydroxychloroquine dose within the first 5 years of treatment predicts this risk.

The study, published on January 17, 2023, in Annals of Internal Medicine, examined the pharmacy records of more than 3,300 adult patients who had been taking hydroxychloroquine for 5 years or more. Risk for hydroxychloroquine retinopathy was estimated over 15 years of medication use according to hydroxychloroquine weight-based dose using the Kaplan–Meier estimator.

Of the patients in the study group, 81 developed hydroxychloroquine retinopathy, mostly mild, with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively.

The authors concluded that higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. ■

Vector illustration of an intubated head in profile

Can rapid-onset opioids replace neuromuscular blockers during intubation?

Tracheal intubation is an effective way to prevent aspiration of gastric contents during surgery; however, concerns have been raised about potential adverse effects, including anaphylaxis and respiratory complications, related to the neuromuscular blockers commonly used in intubation. In a recent study, published in the January 3, 2023, issue of JAMA, a group of French researchers investigated whether rapid-onset opioids would meet the criteria for successful tracheal intubation without major complications.

The randomized, open label, noninferiority trial involved 1,150 adults at risk of aspiration (e.g., fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021.  

Patients received neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium) or remifentanil (3–4 μg/kg) immediately after injection of a hypnotic drug. The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, or severe anaphylactic reaction.

Results of the study indicated that the rate of tracheal intubation on first attempt without major complications was 66.1% in the remifentanil group and 71.6% in the neuromuscular blocker group, a difference that did not meet the prespecified noninferiority margin of −7% and was consistent with statistical inferiority of remifentanil. An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers.

The authors concluded, however, that although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. ■

Four medical personnel surround a patient in a hospital bed. The patient's blood pressure is being measured with a blood pressure cuff and stethoscope.

Baxdrostat may hold promise for treatment of resistant hypertension

Because high levels of aldosterone can cause hypertension, inhibition of aldosterone synthase is essential for controlling BP. According to the authors of a recent paper in the February 2, 2023, issue of NEJM, selective inhibition is difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. However, preclinical and phase 1 studies have shown that baxdrostat holds promise for reducing plasma aldosterone levels but not cortisol levels.

The BrigHTN Investigators conducted a multicenter, placebo-
controlled trial involving 248 patients who had treatment-resistant hypertension with BP of 130/80 mm Hg or higher and who were receiving stable doses of at least 3 antihypertensive agents, including a diuretic. Key exclusion criteria were a mean seated systolic BP of at least 180 mm Hg or a diastolic BP of at least 110 mm Hg, an estimated glomerular filtration rate of less than 45 mL per minute per 1.73 m2
of body-surface area, and uncontrolled diabetes.

Patients were randomly assigned to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo, with a primary end point of the change in systolic BP from baseline to week 12 in each baxdrostat group compared with the placebo group.

Patients in the 1-mg and 2-mg baxdrostat group showed significantly greater decreases in systolic BP than those in the placebo group, while patients in the 0.5-mg group showed smaller decreases. No deaths occurred during the trial, and no serious adverse events were attributed by the investigators to baxdrostat. ■

Heat Map style illustration of a heart, with an EKG graphic to the right side

Torsemide versus furosemide after discharge in patients hospitalized with HF

The majority of patients with symptomatic heart failure (HF) are prescribed loop diuretics to relieve congestion, with furosemide being the most commonly used. However, some recent studies have suggested that torsemide may have beneficial effects on myocardial fibrosis, aldosterone production, sympathetic activation, ventricular modeling, and natriuretic peptides.

Members of the TRANSFORM-HF research group, led by Robert J. Mentz, MD, of the Duke Clinical Research Institute and Kevin J. Anstrom, PhD, of the University of Chapel Hill’s Gillings School of Public Health, conducted an open-label, pragmatic randomized trial involving almost 3,000 patients hospitalized with HF (regardless of ejection fraction) at 60 hospitals in the United States to determine whether torsemide results in decreased mortality compared with furosemide among this patient population. The study was published in the January 17, 2023, issue of JAMA.

Over the 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 47.3% of patients in the torsemide group and 49.3% patients in the furosemide group. In addition, there were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group. The authors concluded that among patients discharged after hospitalization for HF, torsemide did not result in a significant difference in all-cause mortality over 12 months compared with furosemide. However, they said, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. ■



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