ACC 2026 | Two Trials, One Message: Lower LDL-C Targets Deliver Superior CV Outcomes 👉Two landmark trials presented today at #ACC26 in New Orleans converge on the same conclusion: being aggressive with LDL-C lowering saves lives and prevents events — whether in secondary or high-risk primary prevention. 📌 VESALIUS-CV Diabetes Subgroup (JAMA, March 28, 2026) 👉Evolocumab in high-risk primary prevention — no prior MI/stroke, no known significant atherosclerosis, diabetes ∙3,655 patients, median follow-up 4.8 years ∙LDL-C achieved: 52 mg/dL (evolocumab) vs. 111 mg/dL (placebo) at 48 weeks ∙3-P MACE: 5.0% vs. 7.1% — HR 0.69 (95% CI 0.52–0.91), p=0.009 ∙4-P MACE: 7.6% vs. 10.5% — HR 0.69, p=0.001 ∙All-cause mortality: HR 0.76 (95% CI 0.61–0.95) ∙Benefit emerged after year 1 — consistent with atherosclerosis prevention rather than plaque stabilization ∙Median achieved LDL-C at 96 weeks: 44 mg/dL — approaching the extreme-risk threshold 📌 Ez-PAVE (NEJM, March 28, 2026) 👉LDL-C target <55 vs. <70 mg/dL in established ASCVD — a head-to-head RCT ∙3,048 patients, 3-year follow-up, 17 Korean centers ∙Median LDL-C achieved: 56 vs. 66 mg/dL ∙Primary composite (CV death, MI, stroke, revascularization, UA hospitalization): 6.6% vs. 9.7% — HR 0.67 (95% CI 0.52–0.86), p=0.002 ∙Nonfatal MI: HR 0.46 | Any revascularization: HR 0.63 ∙No signal of harm: no excess diabetes, myopathy, or liver toxicity; creatinine elevation was actually lower in the intensive arm ∙Critical gap: only 60.8% reached <55 mg/dL at 3 years; PCSK9i used in only 2.3% — underscoring the implementation crisis in real-world practice 🔑 The Integrated Message ∙The “lower is better” paradigm now has direct RCT support across the CV risk continuum — from primary prevention with diabetes to established ASCVD ∙VESALIUS-CV challenges the binary secondary/primary prevention framework: a diabetic patient without clinical ASCVD already benefits from PCSK9i-level LDL-C reduction ∙Ez-PAVE validates ESC/EAS 2025 guideline targets with hard outcome data — no longer just extrapolated from drug trials ∙The real-world gap remains unacceptable: <25% of ASCVD patients reach <55 mg/dL; <10% receive ezetimibe; ~1% receive PCSK9i ∙Together, these data support a universal aggressive approach: early combination therapy, lower thresholds, and broader access to non-statin agents DOI: 10.1056/NEJMoa2600283 DOI:10.1001/jama.2026.3277 @society_eas @nationallipid @LipidJournal @ACCinTouch
