Ez-PAVE, second randomisation

Presented in LBS.03 at AHA 2026 (Saturday 7 November, Byeong-Keuk Kim, Severance Hospital, Yonsei University, Seoul) and published simultaneously in Circulation. In the 2 by 2 factorial Ez-PAVE trial (3,048 patients with atherosclerotic cardiovascular disease, 17 South Korean centres, January 2021 to July 2022, mean age 64.4, 20.9 percent women, median baseline LDL 76 mg/dL), after the first randomisation to an LDL target below 55 or below 70 mg/dL (reported at ACC 2026: HR 0.67 in favour of the lower target), patients were randomised a second time to initial statin plus ezetimibe (1,525) or statin monotherapy (1,523), with therapy adjusted by protocol to reach the assigned target over 3 years. The primary endpoint (cardiovascular death, non-fatal MI, non-fatal stroke, any revascularisation, hospitalisation for unstable angina) occurred in 128 patients (8.5 percent) on combination therapy versus 119 (7.9 percent) on monotherapy, HR 1.07 (0.83 to 1.37), P=0.596. Combination therapy achieved lower median LDL in both target strategies (53 versus 62 mg/dL with the intensive target, 63 versus 70 with the conventional target); ezetimibe was added to 34.3 and 24.8 percent of monotherapy starters respectively. The effect of the lower target was consistent regardless of the starting regimen (P interaction 0.583). Components and safety (new-onset diabetes 17.1 versus 15.6 percent, muscle symptoms 0.7 versus 0.9) did not differ. Not powered for outcomes, open label, 3 years, East Asian men. The target matters, the starting regimen does not; combination gets there faster.