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 (P<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]; P=0.004) and 4-point MACE by 18% (17.9% versus 21.7%; HR, 0.82 [95% CI, 0.71-0.96]; P=0.012) as well as both MI by 50% (3.0% versus 6.1%; HR, 0.50 [95% CI, 0.36-0.70]; P<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]; P<0.001). There were nominally lower rates of cardiovascular death (2.6% versus 3.7%; HR, 0.66 [95% CI, 0.45-0.96]; P=0.030) and all-cause death (8.2% versus 10.2%; HR, 0.76 [95% CI, 0.60-0.95]; P=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.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Cardiology | |
| Internal Medicine |  |
A confirmation that for LDL-C in this disease situation, the lower the better! However, trial enrollment required LDL-C to be at least 90 mg/dL on optimized therapy, and these findings might not be assumed to apply equally to patients with lower LDL-C levels.
Evolocumab is an effective alternative LDL-lowering treatment in high-risk IHD. The question is what happens with add-on therapy when a patient is already on statins with moderate LDL results, or when side effects compromise the statin therapy.
Patients with prior PCI without prior MI have event rates similar to classic secondary prevention cohorts, yet often receive less intensive LDL-C management. Evolocumab with high intensity statins lowered LDL-C to ~40 mg/dL and halved MI rates, with early benefits seen by 6 months and substantial reductions in urgent coronary revascularization and cardiovascular mortality. Patients may think the “problem is fixed” after a stent, but this is a timely reminder to always optimize advances.