Ground Truths

In recent weeks the results (announced by press release) of 2 major placebo-controlled randomized trials—ZEUS, testing an interleukin-6 (IL-6) blocker vs inflammation, and HORIZON, testing a drug to lower Lp(a), indicated failure to achieve their primary endpoint.Are we maxxed out for new treatments vs heart disease, as this article in the WSJ (←gift link) today asserts? “Cardiovascular drug development is starting to look a bit like the modern oil industry. The easy wells have been tapped. What’s left is in deep water: expensive, technically perilous and less likely to strike oil.”Or is it more complicated? Are the trial results and reasons for failure different?I wrote a recent Ground Truths —The Coronary Artery Inflammation Controversy— on the data (what has been released to date) and my take. But I wanted to vet this with another physician-scientist who is studying atherosclerosis and turned to Prof Marios Georgakis, from the University of Munich, who as I mentioned in the previous piece, wrote a brilliant analysis of ZEUS and is also doing writing about HORIZON.Many years ago we went through a “CV winter” when the biopharma companies largely shunned doing clinical trials for heart disease. They thought the field had been maxxed out. After a lapse of several years, there have many trials undertaken with positive results and substantial progress for better treatments vs heart disease. Both Marios and I remain optimistic that we are a long way from maxing out, as you’ll learn from the podcast. Heart disease is the number one global killer, for both men and women. That’s despite all the progress that has been made to date.Thanks for your support of Ground Truths and to Dr. Julie Kellogg, Vau Geha, Ralph Horwitz, Jessica Coffman, Michael G. Levin, MD, and mopre than 400 others for tuning into my live video with Marios Georgakis! **********************************Ground Truths has 215,000 subscribers from every US state and 214 countries. There are over 310,000 followers of Ground Truths so nearly 100,000 folks who can easily convert to be free subscribers. Please consider doing that…it’s free.Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. If you’re not a subscriber, please join!If you found this interesting PLEASE share it!The proceeds from all voluntary paid subscriptions go to support our summer internship program. It enabled us to accept and support a record number of 62 summer interns that joined us in 2026! These are high school, college and medical students selected from thousands of applicants. We couldn’t do this expanded program without the funds coming in through Ground Truths. Thank you! Get full access to Ground Truths at erictopol.substack.com/subscribe

A couple of weeks ago, the FDA Commissioner published a WSJ oped “The FDA Liberates Women’s Hormone Replacement Therapy” (←gift link) and, with other FDA colleagues, a JAMA essay entitled “Updated Labeling for Menopausal Hormone Therapy” (open-access). That change, and the data cited, led to a series of articles in the days that followed, such as at STAT News “FDA reverses decades-old warning on hormone therapy products for menopause. Agency says the treatments o!fer heart, brain, and bone health benefits” and at the Washington Post “The FDA finally corrects its error on menopause hormone therapy. Women have been needlessly scared away from effective treatments.” If you read through these links, you’ll be confused. Does MHT have proven cognitive benefits? What about a study from 1991 that showed ~50% reduction of fatal heart events with MHT? Or the 35% decreased risk of Alzheimer’s disease? Or the breast cancer increased risk attributed to medroxyprogesterone acetate?I turned to my go-to gynecologist truth teller, Dr. Jen Gunter, to get her review of the evidence. This is a complex topic, with old data from the 2002 Women’s Heath Initiative (WHI), new reports since, population level analysis, changes in preparations of MHT including local delivery, and much more.Here is our conversation which isn’t just about MHT but includes “Big Wellness” marketing direct to middle aged women, the new FDA approved drug for hot flashes, the $14 million cut of the NIH’s Office of Women’s Health , marked increase in philanthropic support of women’s health research, the Surgeon General nominee, ovarian failure, and a lightning round on proven benefits of MHT.Here’s a brief clip on her views of the women’s health “wellness” predatorsWe also discussed the reasons for Dr. Gunter’s planned move next year back to Canada after practicing gynecology for 3 decades in the United States. I referred to a recent GT I wrote about the WHI and the potential favorable impact of MHT on the immune system, as suggested by new data on organ clocks. That finding, which has been replicated, may be linked to healthy aging, extending healthspan.****************************Thanks to the >190,000 Ground Truths subscribers from every US state and 210 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile.If you found this interesting PLEASE share it!Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered.Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.Thank you Debbie Weil, Cynthia Brumfield, Sara Garcia, Harshi Peiris, Ph.D., Liane Moccia, and over 1,000 others for tuning into my live video with Dr. Jen Gunter! Join me for my next live video in the app. Get full access to Ground Truths at erictopol.substack.com/subscribe

Get full access to Ground Truths at erictopol.substack.com/subscribe