For years, guidelines have told clinicians to target an LDL below 55 mg/dL in patients with established cardiovascular disease. There was just one problem: no randomized trial had ever directly compared that target to the previous goal of less than 70. The 2026 ACC/AHA Dyslipidemia Guideline recommended the stricter number on March 13th. Ez-PAVE published in the New England Journal two weeks later. In this episode, we break down the Ez-PAVE trial — 3,048 patients with established ASCVD, randomized to LDL targets of less than 55 vs less than 70 mg/dL over three years. The composite primary endpoint was significant (HR 0.67, p = 0.002). CV death was not. All-cause mortality was flat. Revascularization drove the result. And 39% of patients in the intensive group never reached their own target. • Primary composite: 6.6% (intensive) vs 9.7% (conventional) — HR 0.67 (95% CI 0.52–0.86), p = 0.002 • Absolute risk reduction: 3.1 percentage points over 3 years — NNT ≈ 32 • CV death: HR 0.83 (95% CI 0.42–1.65) — not statistically significant • All-cause mortality: 2.0% vs 1.9% — no difference • Revascularization drove the composite: 4.8% vs 7.5% (HR 0.63) • Only 60.8% of intensive-group patients reached the 55 mg/dL target at 3 years • PCSK9 inhibitor use: just 2.3% in the intensive arm • Castelli Coefficient: 6.3/10 Lee YJ, Lee SJ, Kim JW, et al. Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease. N Engl J Med 2026;394:1365–75. DOI: 10.1056/NEJMoa2600283 ClinicalTrials.gov: NCT04626973