Evolocumab in Patients With Prior Percutaneous Coronary Intervention and No Prior Myocardial Infarction: Results From the VESALIUS-CV Trial.

Abstract (English)

BACKGROUND: The clinical benefit of intensive LDL cholesterol (LDL-C) lowering with evolocumab in patients with prior percutaneous coronary intervention (PCI) but without a prior myocardial infarction (MI) is not established. METHODS: VESALIUS-CV (The Effect of Evolocumabin Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke) randomized patients with atherosclerosis or high-risk diabetes but without prior MI or stroke and with LDL-C ≥90 mg/dL to evolocumab versus placebo. The median follow-up was 4.6 years. The dual primary end points were coronary heart disease death, MI, or ischemic stroke (3-point major adverse cardiovascular event [MACE]) and the same composite plus ischemia-driven revascularization (4-point MACE). For this prespecified subgroup analysis, patients were categorized by whether they had undergone PCI at any time before trial enrollment. RESULTS: Among 12 257 randomized patients, 3627 (29.6%) had undergone prior PCI with a median time between PCI and enrollment of 4 years. Their median age was 66 years, and 30.7% were women. The median LDL-C in a lipid substudy at 48 weeks was 41.5 (26.0-67.0) mg/dL versus 107.0 (84.0-135.0) mg/dL in the evolocumab versus placebo arms (<i>P</i><0.0001). Evolocumab reduced the relative rate of 3-point MACE by 30% (5-year Kaplan-Meier rates 7.0% versus 9.5%; hazard ratio [HR], 0.70 [95% CI, 0.56-0.89]; <i>P</i>=0.004) and 4-point MACE by 18% (17.9% versus 21.7%; HR, 0.82 [95% CI, 0.71-0.96]; <i>P</i>=0.012) as well as both MI by 50% (3.0% versus 6.1%; HR, 0.50 [95% CI, 0.36-0.70]; <i>P</i><0.001), with the effect apparent as soon as 6 months after randomization, and urgent coronary revascularization by 39% (HR, 0.61 [95% CI, 0.46-0.80]; <i>P</i><0.001). There were nominally lower rates of cardiovascular death (2.6% versus 3.7%; HR, 0.66 [95% CI, 0.45-0.96]; <i>P</i>=0.030) and all-cause death (8.2% versus 10.2%; HR, 0.76 [95% CI, 0.60-0.95]; <i>P</i>=0.016) with evolocumab. CONCLUSIONS: Evolocumab reduced the risk of major cardiovascular events in stable patients with prior PCI but no MI. These findings support intensive LDL-C lowering in patients who have undergone PCI even in the absence of prior MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03872401.