THE ROUNDS REPORT
This was the month of the well-designed null. A 14-day ECG patch that didn't stop fainting. A beta-blocker that didn't protect COPD lungs. Extended Paxlovid that didn't touch long COVID. Tenecteplase that added nothing before late basilar thrombectomy. Sound underwhelming? Only if you skip the methods.
Each answers a question we argue about on rounds, and one clear winner emerges: a quarterly siRNA that cuts pancreatitis in severe hypertriglyceridemia. The pearls stay on theme, from HEPA filters to ICS step-down to a village blood pressure program that may prevent dementia.
Here's what you need to know.
THE BIG FIVE GAME-CHANGERS
1. ASPIRED: A 14-Day ECG Patch After Unexplained Syncope Doesn't Reduce Recurrence, but Finds Far More Arrhythmias Hospital Medicine / Diagnostics
In this pragmatic trial at 45 UK hospitals, 2,234 adults with syncope unexplained after ED evaluation were randomized to an immediate 14-day wearable ECG patch or standard care. One-year syncope episodes did not differ (mean 1.37 vs 1.58; IRR 0.89; 95% CI 0.68-1.18; P=0.42). Monitoring detected more clinically significant arrhythmias (22.0% vs 9.0%; OR 2.95; 95% CI 2.28-3.81), led to more pacemakers (6.8% vs 4.6%), and was associated with lower all-cause mortality (1.5% vs 2.9%), a secondary outcome.
Practice implication: Physicians may want to consider early 14-day monitoring as a diagnostic, not preventive, strategy for unexplained syncope, possibly as an alternative to admission for telemetry alone. The mortality signal is hypothesis-generating. Funded by the British Heart Foundation and NHS Research Scotland (non-industry).
2. SHASTA-3 and SHASTA-4: Quarterly Plozasiran Cuts Triglycerides by About 80% and Acute Pancreatitis by 78% Endocrinology / Lipids
Lowering triglycerides was never the goal in severe hypertriglyceridemia; preventing pancreatitis is. These twin phase 3 trials randomized 757 adults with triglycerides of at least 500 mg/dL 2:1 to plozasiran, an APOC3-targeting siRNA given every 3 months, or placebo. Median triglyceride reductions at month 12 were 79% and 81% vs about 27% with placebo (P<0.0001). In the prespecified pooled analysis, acute pancreatitis events fell 78% (P=0.008), including a 100% reduction in the highest-risk subgroup (triglycerides above 880 mg/dL with prior pancreatitis). Treatment-related adverse events leading to discontinuation occurred in 1.4% vs 0.8%.
Practice implication: Alongside olezarsen (February 2026), an antisense agent hitting the same APOC3 pathway, SHASTA adds a quarterly siRNA option with a pancreatitis outcome. Physicians may want to consider referral of patients with recurrent pancreatitis or very high triglycerides. Presented at ESC Congress 2026; journal publication not yet confirmed. Sponsored by Arrowhead Pharmaceuticals (industry).
3. BRONCHIOLE: Metoprolol Does Not Improve Outcomes in COPD Without Cardiovascular DiseasePulmonology
Observational data suggested beta-blockers might reduce exacerbations and death in COPD, but randomized trials had not confirmed it. This open-label, pragmatic phase 4 trial randomized 1,695 patients (mean age 70; 62% female) with COPD, sinus rhythm, and no cardiovascular disease to metoprolol (target 100 mg daily) plus standard care or standard care alone. The 1-year composite of exacerbation, cardiovascular event, or death occurred in 27% vs 30% (HR 0.87; 95% CI 0.73-1.05; P=0.14), with no significant difference in any component. Serious adverse events occurred in 9.4% vs 7.8%.
Practice implication: With BLOCK-COPD (NEJM 2019), which found more exacerbations requiring hospitalization with metoprolol, physicians may want to avoid starting beta-blockers for lung or cardiovascular protection when no cardiac indication exists. Cardioselective agents remain acceptable when one does. Echoes SMART-DECISION (April 2026) and the post-MI meta-analysis (December 2025). Funded by research grants from the Swedish Research Council and others.
4. RECOVER-VITAL: Extended Nirmatrelvir-Ritonavir Fails Across All Three Long COVID PhenotypesInfectious Disease
If viral persistence drives long COVID, a longer antiviral course should help. It didn't. This NIH RECOVER double-blind phase 2 trial at 69 US sites enrolled 959 adults (median age 49; 67% female) with at least 12 weeks of cognitive, autonomic, or exercise-intolerance symptoms in a 1:1:1 randomization to 25 days of nirmatrelvir-ritonavir, 15 days followed by placebo, or placebo. No regimen produced a significant day-90 benefit in any phenotype (25-day regimen vs placebo: cognitive +3.2%, 95% CI -10.4 to 16.8; autonomic -6.4%, 95% CI -18.5 to 5.7; exercise -7.8%, 95% CI -19.5 to 3.8). All groups improved similarly; there were no deaths, and serious adverse events occurred in 4% of participants.
Practice implication: Physicians may want to steer patients away from off-label extended Paxlovid for established long COVID. The parallel improvement in all arms underscores strong placebo effects. Joins HEAL-COVID (colchicine, December 2025) among repurposed drugs that have not delivered. Funded by the NIH (non-industry); Pfizer donated study medication.
5. ATTENTION LATE: Tenecteplase Before Thrombectomy Adds No Benefit in Late-Window Basilar Artery Occlusion Neurology
This randomized trial at 40 Chinese centers enrolled 332 patients with basilar artery occlusion presenting 4.5 to 24 hours after onset to tenecteplase plus thrombectomy or thrombectomy alone. Functional independence at 90 days (mRS 0-2) was identical at 30% in both groups (adjusted rate ratio 0.92; 95% CI 0.67-1.25). Symptomatic intracranial hemorrhage occurred in 5% vs 4%, and 90-day mortality was 40% vs 43%.
Practice implication: Extending TRACE-5 (April 2026) into the late window with a neutral result, this suggests that when thrombectomy is promptly available, adding tenecteplase did not improve outcomes. Generalizability beyond Chinese centers and high baseline mortality warrant caution. Sponsor is an academic hospital; funding not confirmed.
CLINICAL PEARLS THAT MATTER
HEPA Filters Don't Reduce Respiratory Infections in Care Homes (Geriatrics / Infectious Disease) In AFRI-c, a cluster randomized trial in 91 care homes, portable HEPA filters did not reduce respiratory infections per winter among residents (0.99 vs 1.04; adjusted IRR 0.92; 95% CI 0.64-1.33) or staff absenteeism. Long-term care physicians may want to prioritize established infection control measures over filter purchases. AFRI-c - JAMA Internal Medicine
ENRICH-AF: Edoxaban After Intracranial Hemorrhage Trades Ischemic Strokes for Bleeds (Cardiology / Neurology) In 948 AF survivors of intracranial hemorrhage, stroke or systemic embolism did not differ with edoxaban vs non-anticoagulant therapy (11.8% vs 12.8%; HR 0.88; 95% CI 0.61-1.26). Significantly fewer ischemic strokes were offset by an almost threefold excess of hemorrhagic strokes, and major bleeding was higher (11.6% vs 5.2%; HR 2.23; 95% CI 1.39-3.59). Presented at ESC Congress 2026; journal publication pending. ENRICH-AF - ESC Congress 2026
COPERNICOS: Eosinophil-Guided ICS Step-Down in Severe COPD (Pulmonology) Blood eosinophil-guided ICS reduction did not significantly increase severe exacerbations or mortality vs continued triple therapy in patients with COPD, though formal noninferiority was not demonstrated, so the signal is reassuring rather than definitive. Presented at ERS Congress 2026; journal publication pending. COPERNICOS - AJMC interview with the investigators
Village Blood Pressure Control Lowers Dementia Risk at 7 Years (Geriatrics / Neurology) In the China Rural Hypertension Control Program, 326 villages (33,995 adults) were randomized to protocol-based care targeting below 130/80 mmHg or usual care. At 7 years, dementia occurred in 8.85% vs 10.55% (adjusted RR 0.85; 95% CI 0.78-0.91). Presented at ESC Congress 2026; journal publication pending. CRHCP Dementia Analysis - ESC Congress 2026
MONDAY MORNING ROUNDS: 5 KEY DISCUSSION POINTS
The patch diagnoses, it doesn't prevent. In ASPIRED, a 14-day ECG patch did not reduce 1-year syncope recurrence (IRR 0.89; P=0.42) but detected clinically significant arrhythmias in 22.0% vs 9.0%.
Pancreatitis, not just triglycerides. Quarterly plozasiran cut triglycerides 79% to 81% and acute pancreatitis events 78% in SHASTA-3 and SHASTA-4.
No beta-blockers for COPD lungs alone. In BRONCHIOLE, metoprolol did not improve the composite outcome (27% vs 30%; HR 0.87; P=0.14).
Longer Paxlovid is not a long COVID treatment. RECOVER-VITAL found no benefit across any phenotype in 959 patients.
No bridging bonus in late basilar occlusion. In ATTENTION LATE, tenecteplase before thrombectomy yielded identical 90-day functional independence (30% vs 30%).
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