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I have panclass myalgia from all LLT-especially statins (including pitavastatin) and Repatha BA. I uploaded my genome reports into Opus 4.8, and Claude suggested LDN for my mLoy affected macrophages and Rapa for the cytokine release. I can only report that I can tolerate Repatha now and based on my LDL numbers next month I will decide wether to layer in BA. I am not brave enough to throw statins at this thereapy yet.
Oral PCSK9I approved by FDA.
Interesting.
No goodrx price yet. List is mentioned at $300/month.
Has to be taken first thing in the am with no food for 30m. Black coffee, tea, water ok.
Only approved in US for now.
I wonder how long until it’s available in India?
In the meantime, for those interested, repatha is now available on goodrx for aprox $250 per month.
I personally much prefer a shot every 14 days that I don’t have to think about, but obviously the pills will be life changing for many.
With an Amgen card and insurance, it’s 50 for 3 months now. I’m told that most insurance plans these days don’t require prior authorization to get it now. You can go here to find out coveragfe information: Coverage Information | Repatha® (evolocumab) HCP
I’ve always had the impression that PCSk9i were the future LDL-c lowering medication (set to replace statins), but when I looked at data comparing them to statins for ACM and MACE, I was surprised to find that based on the available data, statins beat them.
Here are 2 studies comparing them:
Niu, Q. (2025). Which is the optimal choice in lipid-lowering therapy for reducing major cardiovascular events? A network meta-analysis. Frontiers in Pharmacology. Read the study on PubMed Central
Riesen, W. F. (2025). Lipid-lowering Medications - Statins Versus PCSK9 Inhibitors. Journal of Clinical Cardiology and Cardiovascular Interventions. Read the publication on ResearchGate
This is a big reason, though not the only one, why I have resisted adding a PCSK9i to my lipid lowering stack despite the three meds currently in my stack (4mg/day pitavastatin, 180mg/day bempedoic acid, 10mg/day ezetimibe) not lowering my LDL/ApoB sufficiently. I am waiting for two drugs to appear in the market, both appear close - one to lower ApoB and the other to crush Lp(a). I felt that I can wait on these drugs, because at age 65 my CAC was zero. Had it been any number greater than zero, I’d likely feel forced to spring for a PCSK9i.
That said, I don’t feel the question of ACM vs PCSK9i has been satisfactorily established. We need longer lasting and more focused trials to conclusively resolve this question. My personal choice is not because I’m 100% sure ACM is unaffected by PCSK9i, but simply as a precautionary step. YMMV.
Totally agree here. I expect the PCSK9i meds will show equivalent or nearly-equivalent ACM with longer/better studies. Perhaps statins might provide some additional benefit over and above ApoB-lowering for those whose inflammation isn’t already well-controlled.
Good point. Perhaps a study selecting people with low inflammation would show that PCSK9i have an edge there for ACM and/or MACE.
@qBx123Yk @Davin8r - while waiting for such trials (should they occur), we also have MR. Those seem generally supportive of PCSK9i, though there is some annoying heterogeneity wrt. AD with one showing worrisomely elevated odds for PCSK9i. That said, MR studies are not a flawless tool in the case of PCSK9i and need very careful evaluation. As so often, only time will tell - PCSK9i are still relatively newish in clinical practice and we need more time to amass enough of a track record to allow for more accurate data mining.
ORION-4 is a trial of 15000 participants which is set to evaluate ACM as a secondary end point for inclisiran (Leqvio). Should be out by November.
I found Leqvio to be undewhelming. Barely moved the needle compared to other LLT.
TL, DR , critical, from the start to today, july 19th. Written by GPT 5.6 sol extra-high
Cardiovascular_Health_2026_Global_TLDR_full_thread_1-558.pdf (61.6 KB)
Matt Kaeberlein springs for Repatha.
Why I Started Repatha (And Why I Almost Didn’t) (via Matt Kaeberlein)
In this clinical case review, biogerontologist Dr. Matt Kaeberlein and his personal physician, Dr. Kevin White, evaluate advanced cardiovascular diagnostics and lipid-lowering pharmacology for the early interception of atherosclerotic cardiovascular disease (ASCVD). Standard Coronary Artery Calcium (CAC) non-contrast CT scans quantify calcified, hard plaque but fail to visualize non-calcified, soft plaque—the active, vulnerable atheromatous burden responsible for acute plaque rupture and myocardial infarction. To overcome this diagnostic limitation, Kaeberlein underwent Coronary Computed Tomography Angiography (CCTA) with contrast, coupled with Cleerly AI automated volumetric plaque analysis. Despite maintaining rigorous lifestyle habits (resistance training, cardiovascular exercise, high-quality diet, sleep hygiene), Kaeberlein presented with persistent atherogenic dyslipidemia (ApoB 111 mg/dL, LDL-C 159 mg/dL, Total Cholesterol 209 mg/dL) driven by genetic risk factors and prior early-life lifestyle suboptimalities.
CCTA automated image analysis revealed a low total plaque volume of 16.1 mm³ (Percent Atheroma Volume = 0.5%), classifying him as Stage 1 early ASCVD. However, 14.0 mm³ (87%) of this total plaque volume comprised soft, non-calcified plaque, with only 2.1 mm³ calcified. While conventional primary care often dismisses low-volume soft plaque in mid-50s adults as age-appropriate, proactive healthspan medicine identifies soft plaque as active, progressive vascular pathology requiring aggressive early intervention.
To halt plaque progression and induce atheroma regression, Kaeberlein initiated Repatha (evolocumab), a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). By blocking PCSK9-mediated lysosomal degradation of hepatic low-density lipoprotein receptors (LDLRs), evolocumab increases LDLR cell-surface density, accelerating plasma clearance of ApoB-containing lipoproteins. After 6 to 8 months of monotherapy, Kaeberlein achieved a 64% reduction in LDL-C (down to 57 mg/dL), a 49% reduction in ApoB (down to 57 mg/dL), and a 48% reduction in Total Cholesterol (down to 109 mg/dL). Double-blind randomized controlled trials, including GLAGOV and FOURIER, confirm that reducing LDL-C below 50 mg/dL via PCSK9 inhibition halts atheroma progression, induces total atheroma volume regression, and thickens protective fibrous caps. This case highlights that lifestyle optimization is frequently insufficient to overcome genetic dyslipidemia, requiring direct anatomical imaging via CCTA and targeted lipid-lowering pharmacology to prevent clinical ASCVD events.
Good. He could probably have reached the same LDL levels (57) on a statin. Surprised to learn he didn’t seem to be on any cholesterol-reducing frugs earlier.
Odd isn’t it?
85-year-old
Statin + exercise + diet = Current LDL 41, and that is not the lowest I have been.
I’m a little disappointed by how sparse his discussion was. Would’ve been nice if he had discussed why he went for a PCSK9i rather than a statin plus ezetimibe. Very little color here, just “blah, repatha, thank you!”. But I’ve noticed this before about Matt - areas outside of his immediate proffesional occupation get short shrift. How is it that until recently he seemed to know so little about CV health, imaging, atherosclerosis, available drugs and so on? I mean, I’m a complete layman, and I’ve been up on all that for years. Wonders never cease.
I don’t think ACM is that important or feasible for most here. The background CVD related deaths has to be large so the drug can reduce it enough so that there’s a signal. For that to happen you have to have a high risk group that’s not comparable to most here.
For example, a group with type 2 diabetes and high lipids have high risk. Using a drug to lower CVD related mortality to improve all-cause mortality says nothing about the group with low mortality from CVD. In a group with zero risk for CVD, there would be no upside.
The amounts of events are just too small enough to either detect harm, or benefit. In high risk groups there are multiple drugs proven to reduce total mortality in trials: simvastatin, rosuvastatin, alirocumab, etc.
MACE is very relevant for healthspan, heart attacks and strokes are no fun, so this is important in of itself. We can infer based on MR data, basic logic and extrapolation on possible longevity bottlenecks and longevity benefits from many of these drugs as well, but it’s not something that will come from trials.
So a drug that has MACE data but not ACM isn’t that big of a deal, IMO, and the lower risk the group the less likely it becomes it can detect ACM.
