Eric J. Topol

Metformin at the Time of COVID‐19 Infection and Risk of Long COVID: A Target Trial Emulation Study

Our objective was to evaluate metformin prescribed at the time of SARS‐CoV‐2 infection on the risk of developing Long COVID (LC) in electronic health record data. We conducted a new user analysis of metformin prescribed within 6 days of documented infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) versus experimental control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast. Inclusion criteria: a clinic visit in the 0–6 months and the 6–12 months before infection. Exclusion criteria: metformin or control within 12 months. Primary outcome: LC or death (LC/D), to address death as a competing risk, among patients prescribed drug within Days 0–6 of infection. LC was defined by diagnosis code or computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log‐linear model. After weighting, there were 248 in the metformin and control groups; the average age was 53 (16); 16% were Black; and 16% were Hispanic. In the primary analysis, 10/248 (4.0%) in the metformin group developed LC/D versus 21/248 (8.5%) in the control group, adjusted risk ratio (aRR) 0.47 (95% CI 0.25–0.89, p = 0.02). For prescriptions on Days 0–1 relative to infection, aRR was 0.39 (95% CI 0.12–1.24); for prescriptions on Days 0–14, the aRR was 0.75 (95% CI 0.52–1.08). In this observational analysis, metformin prescribed within a week of documented SARS‐CoV‐2 infection was associated with a 53% lower risk of LC over 6 months than comparator medications. With the aRR of 0.47 (95% CI 0.25–0.89), any risk reduction between 75% and 11% is highly compatible with our data. This analysis of electronic health record diagnoses is important for the reproducibility of clinical trial results that ascertained the same outcome but via participant‐report.

Nine classes of pharmacologic agents inhibited intimal proliferation in >50 animal studies, but none reproducibly reduced human coronary restenosis due to interspecies differences.

Animal restenosis models are hypothesis-generating; human studies required before any translational relevance.

Intramural methotrexate fails to reduce neointimal thickening compared with saline after balloon angioplasty.

Local delivery may circumvent systemic toxicity limits; leaves open clinical efficacy for post-angioplasty restenosis.

Preserving clinical skills in the age of AI assistance

The rise of agentic AI teammates in medicine

AF complicating acute MI is linked to ~30% higher 30-day mortality.

Atrial fibrillation occurring in the setting of acute myocardial infarction is an independent predictor of stroke and increased 30-day mortality, suggesting a need for more aggressive management.

MAR 1997LincoffJournal of the American College of Cardiology

Sustained intracoronary delivery of dexamethasone by a novel polymer-coated stent achieved 3,000-fold higher tissue concentrations at 28 days but did not decrease neointimal hyperplasia in pigs.

A novel intravascular eluting stent utilizing high molecular weight PLLA provides sustained, site-specific delivery of dexamethasone to the porcine coronary artery wall for up to 28 days, though it does not reduce neointimal hyperplasia.

Abciximab bolus plus infusion increases thrombocytopenia to ~5% vs. bolus alone or placebo.

Bolus-plus-infusion abciximab raises thrombocytopenia risk in high-risk PCI; reinforces platelet monitoring in this regimen.

JUN 1987TopolJournal of the American College of Cardiology

IV tPA increases early infarct-artery patency ~4.4-fold vs placebo in acute MI.

Supports intravenous tPA for early recanalization in acute MI; confirms thrombolytic superiority over placebo in this RCT.

Aspirin resistance linked to ~3-fold higher risk of death, MI, or CVA in stable CVD.

Aspirin resistance in stable cardiovascular patients is associated with a greater than threefold increased risk of major adverse cardiovascular events.

FEB 2000TopolCirculation

Recognition of the Importance of Embolization in Atherosclerotic Vascular Disease

MAR 1994HarringtonJournal of the American College of Cardiology

Post-thrombolysis thrombocytopenia affects ~16% of AMI patients and is linked to excess hemorrhage and mortality.

Clinical trial analysis demonstrates higher bleeding and in-hospital mortality with post-thrombolytic thrombocytopenia in myocardial infarction, suggesting a need for daily platelet monitoring.

Tokenising the patient journey: from records to representations

MAR 2000BhattJournal of the American College of Cardiology

Abciximab during PCI reduces one-year mortality ~36% vs placebo in diabetic patients.

Abciximab therapy at the time of PCI significantly reduces one-year mortality in diabetic patients, particularly those with insulin resistance or undergoing multivessel intervention.

From Reactive Care to Predictive Prevention

Humanoid robots in the operating room: a framework for staged integration of embodied AI in surgery

Perspective examines integration of humanoid robots in surgery, suggesting staged deployment for improved outcomes.

AUG 1993KleimanJournal of the American College of Cardiology

Maximal platelet inhibition was achieved at 0.25 mg/kg m7E3 Fab; infarct-related artery patency was 92% with m7E3 Fab vs 56% in controls, with major bleeding in 25% vs 50% respectively.

The addition of m7E3 Fab to thrombolytic therapy in acute myocardial infarction safely achieves profound platelet inhibition and may improve coronary patency.

Elevated cTnI post-PCI is linked to higher death or MI despite a null primary composite.

Elevated cTnI after PCI in patients with ACS is a useful prognostic indicator associated with worse 90-day clinical outcomes, particularly death or infarction.