THE ROUNDS REPORT
Fish oil - for the skeptics and advocates alike - reduced CV events in hemodialysis patients. PCSK9 inhibitors finally work for primary prevention. And tramadol, one of our most prescribed pain medications, barely works at all.
Between mid-October and mid-January, seven major clinical trials published results that will help us rethink how we've been practicing medicine. These studies span cardiology, infectious disease, nephrology, neurology, pain management, and endocrinology, each one delivering data that may reshape treatment protocols.
Without further ado, let’s get to it.
THE BIG SEVEN GAME-CHANGERS
1. PCSK9 Inhibitors Finally Prove Their Worth in Primary Prevention
The VESALIUS-CV trial just answered the question we've been waiting on for years: do PCSK9 inhibitors work for primary prevention?
12,257 patients across 774 sites in 33 countries, median 4.6 years follow-up. The primary outcome (cardiovascular death, MI, ischemic stroke, or coronary revascularization) occurred in 6.2% of the evolocumab group versus 8.0% of placebo (HR 0.75, P<0.001). That's a 25% relative risk reduction.
The four-point MACE outcome was even more impressive: HR 0.81 (P<0.001). MI specifically? Reduced by 36%.
LDL-C achieved: 45 mg/dL in the evolocumab group versus 109 mg/dL in placebo. We're talking about LDL levels that were unthinkable with statins alone.
Clinical reality check: This trial enrolled patients at high cardiovascular risk but without prior MI or stroke. This represents the first Level 1 evidence that aggressive LDL lowering with PCSK9 inhibitors may prevent first events, not just recurrent events.
2. Fish Oil Actually Works (If You're on Hemodialysis)
The PISCES trial delivered results that omega-3 skeptics can't ignore: 43% reduction in cardiovascular events for hemodialysis patients.
1,228 patients (mean age 64.3 years, 62% male) at 26 sites in Canada and Australia received either 4g omega-3 daily (1.6g EPA + 0.8g DHA) or corn oil placebo for a median 3.5 years.
Primary outcome (cardiovascular death, MI, stroke, or peripheral vascular disease event/amputation) occurred in 32.7% of omega-3 group versus 43.6% of placebo (HR 0.57, P<0.001).
Individual outcomes? Cardiac death: HR 0.55. MI: HR 0.56. Stroke: HR 0.37. PVD/amputation: HR 0.57. Every endpoint moved in the right direction.
Context: Hemodialysis patients face 18% annual mortality, primarily from cardiovascular disease. This is the first intervention to show such a dramatic benefit in this population.
3. The First New Oral Gonorrhea Antibiotic in Decades
The zoliflodacin trial marks a breakthrough in treating drug-resistant gonorrhea: a completely new antibiotic class with no cross-resistance to existing options.
930 participants (mean age 29.7 years, 88% male) across 17 outpatient clinics in 5 countries (Belgium, Netherlands, South Africa, Thailand, USA) received either zoliflodacin or standard ceftriaxone plus azithromycin.
Urogenital cure rates: 90.9% for zoliflodacin versus 96.2% for combination therapy. The difference of 5.3% (95% CI 1.4-8.6) fell within the predefined 12% noninferiority margin.
Zoliflodacin is a spiropyrimidinetrione class antibiotic targeting bacterial type II topoisomerases differently than fluoroquinolones. No cross-resistance = critical advantage as gonorrhea continues developing resistance.
FDA approved December 12, 2025 as Nuzolvence.
4. Spinal Manipulation Doesn't Beat Self-Management for Back Pain
The PACBACK trial challenges decades of chiropractic orthodoxy: spinal manipulative therapy (SMT) offers no additional benefit beyond supervised self-management.
1,000 participants (mean age 47, 58% female) with acute/subacute low back pain at moderate-high risk for chronicity were enrolled at 3 US research clinics (University of Minnesota, University of Pittsburgh). 2×2 factorial RCT with 12-month follow-up using Roland-Morris Disability Questionnaire.
Supervised self-management (SSM) versus medical care: mean difference -1.2 points (95% CI -1.9 to -0.5). Combined SSM + SMT versus medical care: -1.1 points (95% CI -1.9 to -0.3).
But SMT alone versus medical care? -0.4 points (95% CI -1.2 to 0.4, P=0.24). Not significant.
50% disability reduction at 12 months: 67% in SSM groups versus 54% in SMT alone or medical care groups.
Clinical reality check: Self-management education works. Adding expensive spinal manipulation doesn't improve outcomes.
5. AI-Powered Diabetes Prevention Works as Well as Human Coaching
The AI-DPP trial demonstrates that artificial intelligence can match human coaches in preventing diabetes, with higher engagement and completion rates.
368 participants (median age 58 years, 71% female, 27% Black, 6% Hispanic) were randomized to either AI-powered DPP via mobile app or human-led DPP (both remote delivery during COVID-19 pandemic).
Primary composite outcome (maintaining HbA1c <6.5% plus achieving ≥5% weight loss, or ≥4% weight loss + ≥150 min/week activity, or HbA1c reduction ≥0.2%): 31.7% AI-DPP versus 31.9% human-led DPP, meeting the noninferiority threshold.
Program initiation: 93.4% AI-DPP versus 82.7% human-led (P=0.001). Completion: 63.9% AI-DPP versus 50.3% human-led (P=0.008).
Translation: The AI app delivered personalized push notifications based on weight, diet, and activity data. "Looks like you're at the grocery store, Rita! Want a quick list of high-fiber snacks?"
Accessibility advantage: Always available, no staffing shortages, fully automated.
6. Anticoagulation After AFib Ablation: Aspirin May Be Enough
The OCEAN trial challenges our reflexive continuation of anticoagulation after successful AFib ablation: aspirin performed comparably to rivaroxaban with less bleeding.
1,284 patients (mean age 66, 71.5% male) who had undergone successful AF catheter ablation at least 1 year prior with CHA₂DS₂-VASc score ≥1 (or ≥2 for women/vascular disease patients) were randomized to rivaroxaban 15mg daily versus aspirin 70-120mg daily, followed for 3 years.
Primary outcome (stroke, systemic embolism, or new covert embolic stroke ≥15mm on MRI): 0.8% rivaroxaban versus 1.4% aspirin (RR 0.56, 95% CI 0.19-1.65, P=0.28). Not significant.
Event rates: 0.31 versus 0.66 per 100 patient-years. Both extremely low.
Safety: Fatal or major bleeding occurred in 1.6% rivaroxaban versus 0.6% aspirin (HR 2.51, 95% CI 0.79-7.95). Minor bleeding significantly higher with rivaroxaban.
Clinical reality check: For patients at low-moderate stroke risk who are at least 1 year post-successful ablation, the stroke rate is so low that bleeding risk outweighs anticoagulation benefit.
7. Tramadol: Minimal Benefit, Doubled Adverse Events
The tramadol meta-analysis delivers a devastating verdict on one of our most commonly prescribed opioids: it barely works and doubles serious adverse events.
19 randomized clinical trials involving 6,506 participants with chronic pain (neuropathic pain, osteoarthritis, chronic low back pain, fibromyalgia). Treatment periods 2-16 weeks.
Pain reduction: Mean difference -0.93 points on numerical rating scale (95% CI -1.26 to -0.60). Statistically significant but below the predefined minimal important difference of 1.0 point.
Serious adverse events: OR 2.13 (95% CI 1.29-3.51, P=0.001), driven primarily by cardiac events (chest pain, coronary artery disease, congestive heart failure) and neoplasms.
Non-serious adverse events increased significantly: Nausea (NNH 7), dizziness (NNH 8), constipation (NNH 9), somnolence (NNH 13).
Clinical reality check: Tramadol provides minimal pain relief that doesn't meet clinical significance thresholds while doubling serious harm. The risks outweigh the limited benefits.
CLINICAL PEARLS THAT MATTER
1. GLP-1 Agonists Reduce Rheumatic Disease Flares
RA patients on DMARDs who also received GLP-1 receptor agonists experienced fewer disease flares compared to those on DMARDs alone. Early evidence suggests GLP-1s may have anti-inflammatory effects independent of their metabolic benefits. Multiple studies presented at ACR Convergence 2025 demonstrated reduced arthritis activity and improved joint outcomes. These findings may be relevant when discussing treatment options with RA patients who have metabolic comorbidities.
2. Peritoneal Dialysis Preserves Cognition Better Than Hemodialysis
Meta-analysis of 195,774 patients showed peritoneal dialysis associated with significantly lower cognitive impairment risk compared to hemodialysis (RR 0.634, 95% CI 0.508-0.790). Likely related to more stable hemodynamics and reduced cerebral hypoperfusion episodes. Cognitive preservation may be an additional consideration in dialysis modality discussions with CKD patients.
3. Severe Vitamin D Deficiency (<10 ng/mL) Matters in CKD
While general vitamin D supplementation guidelines target levels >30 ng/mL, CKD patients with levels <10 ng/mL face significantly increased risks for hyperparathyroidism progression and cardiovascular complications. Aggressive screening and repletion to >30 ng/mL is recommended in evidence-based guidelines, especially in advanced CKD where deficiency prevalence exceeds 80%.
MONDAY MORNING ROUNDS: 5 KEY DISCUSSION POINTS
1. Primary Prevention with PCSK9 Inhibitors
The VESALIUS-CV trial showed 25% cardiovascular risk reduction (HR 0.75) in high-risk patients without prior MI or stroke. LDL achieved: 45 mg/dL versus 109 mg/dL placebo. First Level 1 evidence for PCSK9 inhibitors in primary prevention. MI reduced 36%.
2. Omega-3 Fatty Acids for Hemodialysis Patients
PISCES trial showed 43% reduction in cardiovascular events (HR 0.57) with 4g daily omega-3 supplementation. Individual outcomes: cardiac death HR 0.55, MI HR 0.56, stroke HR 0.37. First intervention with this magnitude of benefit in hemodialysis population.
3. New Gonorrhea Treatment Without Cross-Resistance
Zoliflodacin (FDA-approved December 2025) demonstrated 90.9% cure rate for urogenital gonorrhea. Spiropyrimidinetrione class with no cross-resistance to fluoroquinolones provides a critical advantage as resistance increases. First new oral option in decades.
4. Spinal Manipulation Adds No Benefit for Back Pain
PACBACK trial found spinal manipulative therapy alone showed no significant improvement over medical care (P=0.24). Supervised self-management reduced disability (-1.2 points) while SMT alone didn't. Education and self-management work; expensive manipulation doesn't add benefit.
5. Tramadol Risks Outweigh Benefits
Meta-analysis of 6,506 patients demonstrated tramadol provided minimal pain reduction (-0.93 points NRS) below clinical significance threshold. Serious adverse events doubled (OR 2.13), primarily cardiac events. Harms outweigh limited benefits for chronic pain management.
ESSENTIAL READING BY SUBSPECIALTY
Cardiology
• VESALIUS-CV: Evolocumab for Primary Prevention - NEJM
• OCEAN: Anticoagulation After AFib Ablation - NEJM
Infectious Disease
• Zoliflodacin for Gonorrhea - Lancet
Musculoskeletal Medicine
• PACBACK: Self-Management vs Spinal Manipulation - JAMA
Endocrinology
• AI-DPP: AI vs Human Coaching for Diabetes Prevention - JAMA
Disclaimer
The content provided in The Rounds Report is for educational and informational purposes only and does not constitute medical advice, diagnosis, treatment recommendations, or professional medical guidance. This newsletter presents summaries and analysis of published medical research and should not be used as a substitute for professional medical judgment, clinical decision-making, or consultation with qualified healthcare providers. Always consult with appropriate medical professionals and refer to original research sources before making any clinical decisions. The Rounds Report does not establish a doctor-patient relationship and readers should not rely on this content for patient care decisions.
© 2026 The Rounds Report. All rights reserved.