The Hallway Consult — Issue #17: VTE Anticoagulation, Cancer PE Workup, and Preschool Wheeze

For years the apixaban-versus-rivaroxaban decision for acute VTE at discharge was driven largely by observational data, pharmacology, and institutional habit rather than a randomized trial. The COBRRA trial is the head-to-head comparison that did not exist until now.

Castellucci and colleagues randomized 2,760 patients with acute symptomatic pulmonary embolism or proximal deep-vein thrombosis 1:1 to three months of apixaban (10 mg twice daily for seven days, then 5 mg twice daily) or rivaroxaban (15 mg twice daily for 21 days, then 20 mg daily). The trial was open-label with blinded endpoint adjudication, conducted internationally.

The primary outcome was clinically relevant bleeding — a composite of major bleeding or clinically relevant nonmajor bleeding — at three months. The numbers are hard to wave away: 3.3% in the apixaban arm versus 7.1% in the rivaroxaban arm, a relative risk of 0.46 (p<0.001). That is more than a 50% reduction in clinically relevant bleeding. Efficacy was preserved — recurrent VTE rates were not significantly different between the groups, and there were no bleeding-related deaths in either arm.

The accompanying editorial in NEJM called the results "striking" and concluded that for many patients with acute VTE, the choice of anticoagulant is no longer a toss-up. The authors hypothesize that the higher initial loading dose of rivaroxaban — 15 mg twice daily for the first three weeks — may explain the difference, since most of the separation in outcomes occurred during that early dosing period.

The practical ED implication is straightforward. When you are discharging a patient with newly diagnosed DVT or PE who is a candidate for oral anticoagulation, apixaban is now the evidence-based default over rivaroxaban. There is no longer a meaningful counterargument for routine use of rivaroxaban based on efficacy — and the bleeding data has moved decisively.

Bottom line: In the first head-to-head randomized trial of apixaban versus rivaroxaban for acute VTE, apixaban produced more than 50% less clinically relevant bleeding with equivalent efficacy. For the ED discharge decision, apixaban is now the evidence-based first choice.

Castellucci LA, et al. Bleeding Risk with Apixaban vs. Rivaroxaban in Acute Venous Thromboembolism. N Engl J Med. 2026;394(11):1051-1060. doi:10.1056/NEJMoa2510703.

The clinical reflex in cancer patients with suspected PE has been simple: just go straight to CT. Cancer elevates D-dimer, disrupts pretest probability calculus, and the stakes of a missed PE are high. The question the Hydra trial asked is whether the YEARS algorithm — which uses a doubled D-dimer threshold of 1000 ng/mL in patients with zero clinical criteria — can safely replace the reflex CTPA in this population.

Akerboom and colleagues ran an open-label, randomized, noninferiority trial across 21 hospitals in six countries, enrolling 698 patients with active cancer and suspected acute PE between 2019 and 2025. Patients were randomized to either a YEARS-guided strategy (n=352) or direct CTPA (n=346). The primary outcome was symptomatic VTE or PE-related death within 90 days after PE was ruled out at baseline.

The 90-day VTE or PE-related death rate was 1.8% in the YEARS arm versus 5.5% in the CTPA-only arm — an absolute difference of -3.7% that met the prespecified noninferiority margin of 2.6%. Importantly, 77 patients (22%) in the YEARS arm avoided CTPA entirely.

The important caveat: 78% of patients in the YEARS arm still underwent CTPA. The algorithm skipped imaging only in a minority — those with zero YEARS criteria and a D-dimer below 1000 ng/mL. In practice, most cancer patients will still end up scanned. The utility of this approach lies not in replacing CT as a broad strategy, but in identifying a specific low-risk subgroup who can be safely spared the radiation, contrast, and workflow cost of imaging.

For the ED, the actionable message is narrow but real: a cancer patient with suspected PE who has zero YEARS items and a D-dimer below 1000 ng/mL can be ruled out without CTPA, and this trial provides the first randomized evidence to support that in an active-cancer cohort specifically.

Bottom line: In cancer patients with suspected PE, a YEARS-guided strategy was noninferior to immediate CTPA for 90-day VTE outcomes. About 22% of patients in the YEARS arm avoided imaging entirely — but most still got scanned. YEARS can safely spare a minority of low-risk cancer patients from CT; it does not replace CT as the default in this population.

Akerboom V, et al. YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism in Patients With Cancer: A Randomized Clinical Trial (Hydra). JAMA. 2026.

Preschool wheeze occupies an awkward clinical space. It does not reliably respond to standard asthma inhalers the way older children do, viral infections are often the trigger, and there is a persistent clinical intuition — backed by some smaller studies — that atypical bacteria like Chlamydia and Mycoplasma may be contributing in a subset. That intuition has driven azithromycin prescribing in wheezing toddlers for years. The AZ-SWED trial gave it a real test.

Researchers enrolled 840 children between 18 and 59 months of age across eight pediatric EDs in the United States and randomized them to a 5-day course of azithromycin or placebo, on top of standard care including bronchodilators and systemic corticosteroids. The primary outcome was wheezing symptom severity over five days, measured using a validated caregiver-reported tool.

Azithromycin did not lead to a greater reduction in symptom severity than placebo. The result held even in the subgroup of children who had bacteria detected on nasopharyngeal swab — which matters, because that is the population in whom the antibiotic rationale was strongest. Secondary outcomes — including hospitalization rate, ED and hospital length of stay, and return visits within 72 hours — were all similar between groups. Notably, approximately half of enrolled children required hospitalization, reflecting the severity of this population.

This is a straightforward negative trial in a population where the temptation to do something is high. The wheeze is scary, the parent is anxious, the child looks miserable, and azithromycin feels like covering a base. What AZ-SWED says is that the base does not need covering — not even when there is microbiologic evidence of bacterial colonization. The treatment adds nothing clinically useful and comes with real costs: antibiotic resistance, disruption of the developing microbiome, and false reassurance that the underlying wheezing mechanism has been addressed.

The practical upshot: if your ED has an informal culture of sending wheezing toddlers home with a Z-pack "just in case," this trial is the evidence to stop that practice.

Bottom line: In preschool children with moderate-to-severe acute wheezing, azithromycin did not reduce symptom severity compared to placebo — even in children with nasopharyngeal bacteria. The Z-pack reflex for wheezing toddlers is not supported by evidence and should stop.

AZ-SWED Trial Group (PECARN). Azithromycin for Preschoolers with Wheezing in the Emergency Department. N Engl J Med. 2026. doi:10.1056/NEJMoa2516505.

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— The Hallway Consult team