Clinical Takeaway / TL;DR
| Domain | Key Finding | Evidence Level |
| 2026 Guidelines | ACC/AHA replaces 2018 cholesterol guidance; LDL-C treatment targets are back, with tighter thresholds for high- and very-high-risk patients | COR 1 / Level A |
| Secondary Prevention Target | LDL-C <55 mg/dL (non-HDL-C <85 mg/dL) in most patients with established ASCVD; statin + ezetimibe + PCSK9 inhibitor cascade if needed | COR 1 / Level A |
| Primary Prevention Target | High-intensity statin for ≥10% 10-year ASCVD risk (goal LDL-C <70 mg/dL); earlier treatment now recommended for subclinical atherosclerosis on CAC or CT | COR 1 / Level A |
| CORALreef Lipids Trial | Enlicitide, an oral PCSK9 inhibitor, reduced LDL-C by 57.1% at 24 weeks (vs. +3% placebo); 67.5% of patients reached <55 mg/dL; safety profile equivalent to placebo | Phase 3 RCT |
| CORALreef AddOn (NEW) | Head-to-head vs. bempedoic acid, ezetimibe, and BA+EZE on statin background: enlicitide reduced LDL-C by 64.6% at 56 days — 28–57 percentage points greater than all comparators (all P<0.001); 78.2% reached <55 mg/dL vs. 20% on BA+EZE | Phase 3 Active-Comparator RCT |
| LDL Causality | Genetic, Mendelian randomization, and RCT data unanimously confirm LDL-C (and ApoB) as causal drivers of atherosclerosis; denialism is not a clinical position — it is a hazard | Overwhelming / Meta-analytic |
| Ez-PAVE Trial (NEW) | First head-to-head RCT of LDL-C targets: targeting <55 mg/dL reduced 3-year MACE by 33% vs. targeting <70 mg/dL (HR 0.67, P=0.002) in established ASCVD patients | Phase 3 Open-Label RCT |
| VESALIUS-CV Subgroup (NEW) | Evolocumab reduced first MACE by 31% (HR 0.69) in primary prevention patients with diabetes and no known atherosclerosis — extends PCSK9 benefit upstream for the first time | Prespecified Subgroup / Phase 3 RCT |
I am tired of watching people die preventable deaths because someone on the internet convinced them that statins are a pharmaceutical conspiracy, that LDL cholesterol doesn't cause heart disease, or that their body "needs" high cholesterol to function. These are not heterodox scientific positions. They are misinformation — and in my clinical world, misinformation has a body count.
This week: the 2026 ACC/AHA Dyslipidemia Guideline, the Ez-PAVE head-to-head target trial, VESALIUS-CV upstream primary prevention data, and the world's first oral PCSK9 inhibitor to pass Phase 3. The science on LDL is not just settled — it is accelerating. The deniers didn't get the memo. Allow me to deliver it.