Some take aways from what we know about HORIZONS phase 3 trial of Lp(a) lowering 1. We know very little. We only know the primary endpoint in the entire population. 2. We do not know if some subgroups may have benefited more like those with a higher baseline Lp(a). 3. Do those who were not on dual or single anti platelet therapy benefit? 4. Did efficacy vary by baseline and on treatment LDL? 5. Did efficacy vary by achieved Lp(a)? 6. We need more sophisticated analyses of the particle composition and oxidizing potential of the patient’s Lp(a) particle to assess for heterogeneity in response. 7. Were the results different in MI patients vs stroke vs PAD patients? These vascular beds behave differently in response to therapeutic interventions. 8. Were the results different in patients with single vessel disease vs multivessel disease where there were more targets for modification. 9. This was a time to first event analysis and not a time to any event analysis (a multiple event analysis). A multiple event analysis captures disease burden and may be more highly powered. 10. For those who were on dual antiplatelet therapies, once these were discontinued, was there an event reduction which would suggest optimal antiplatelet therapy may have reduced residual risk so much it could not be modified? 11. Much has been made of observational data suggesting aspirin may modify risk in patients with an elevated Lp(a). Was there an interaction with aspirin therapy ? 12. Mendelian randomization / genetics captures lifetime exposure and not several years of exposure as in this trial. Were the KM curves diverging late suggesting prolonged therapy might have been needed? 13. Were the assumptions regarding the magnitude of the potential efficacy signal too optimistic and was the trial underpowered? 14. In a trial this long patients may go missing. How good was the follow up? Was there informative censoring? 15. The results of primary prevention trials where LDL lowering and antiplatelet therapy may not have been as aggressive may still show benefit. 16. This ONE trial does not negate the potential causal role of Lp(a). The LDL and antiplatelet therapy may have reduced residual risk so much that there was very little risk to be modified. A trial Lp(a) lowering only would share more light on this question (a trial will never be done). What would happen if all patients were on Lp(a) lowering therapy. Would LDL lowering further improve outcomes? We don’t know for sure. 17. Was there an interaction with CRP, gender age risk score? 18. Obviously there are more questions than answers at this point. I raise these questions as exploratory hypotheses, to further our understanding of the biology, not to salvage a neutral trial. We all anxiously await the full recitation of results and answers to these questions as well as others. Thank you to the patients who participated.

HE❤️RT-IVERSARY WEEK💜❤️💜 “TIN MAN” VIDEO DROPS 8/19 on ⁦@YouTube⁩ ⁦@Spotify⁩

Eli Lilly to allow more patients to apply for special access to unapproved obesity drug. Doctors seeking early access to unapproved retatrutide after Lilly granted drug to 79-year-old patient. statnews.com/2026/08/03/eli-… via @statnews

What was the last thing you accomplished that seemed impossible?

⭐ Bone Thugs-N-Harmony received a star on the Hollywood Walk of Fame today!

Great read challenging the narrative that #GenZ is too soft for medicine: "Medicine doesn’t suffer from a grit shortage. It suffers from misplaced grit." "For decades, the system has demanded toughness in exactly the wrong places, tolerating dysfunctional technology, absorbing endless documentation, and compensating for broken workflows. We framed that endurance as professionalism. Burnout happened because caring was buried under work that never should have been theirs to begin with." "Gen Z is less willing to make peace with that reality. In interviews, they ask questions many organizations aren’t prepared to answer. Why does a physician spend hours managing inbox messages and insurance appeals? Why is exhaustion praised as commitment?" "From an executive seat, I understand the reflex to bristle at these questions. Redesigning workflows, confronting misaligned incentives, or undoing bureaucratic creep is far harder than telling people to toughen up. It’s easier to recruit around burnout than to remove its causes." "All of this puts Gen Z on a collision course with institutions still built around older assumptions: that suffering proves seriousness, that questioning systems undermines authority, that the job should hurt if it matters." "Gen Z isn’t here to save medicine by being tougher. They may save it by forcing leadership to confront what it has long avoided. American health care doesn’t need harder clinicians nearly as much as it needs to stop grinding them down. If that insistence makes leaders uncomfortable, it may be because it lands close to the truth." statnews.com/2026/07/07/gen-…

This Independence Day, @PresAmerMed Willie Underwood III, MD, MSc, MPH shares a powerful reminder: physicians have been helping shape America since its founding, and their leadership is needed now more than ever. As our nation marks 250 years, let’s honor the legacy of the physician signers of the Declaration of Independence and continue the work of building a healthier, stronger future for all. 🇺🇸 Read more: spr.ly/6017BDNusZ