GLAGOV Trial: Evolocumab on CAD Progression

GLAGOV Trial: Effect of Evolocumab on Coronary Disease Progression in Statin-Treated Patients

The GLAGOV trial is a double-blind, placebo-controlled, randomized study designed to assess the impact of PCSK9 inhibition with evolocumab on the progression of coronary atherosclerosis in patients already undergoing statin therapy.

Objective:

The primary objective of the trial was to evaluate whether adding evolocumab to statin therapy would slow or reverse the progression of coronary atherosclerosis in statin-treated patients.

Study Population:

  • Total Patients: 968
  • Inclusion Criteria:
    • Patients aged 18 years and older, indicated for coronary angiography.
    • Stable on lipid therapy or statin intolerant.
    • Fasting LDL-C ≥ 80 mg/dL (or ≥ 60 mg/dL with risk factors).
    • Coronary heart disease with >20% stenosis or prior PCI.
    • Target artery accessible for IVUS with >50% stenosis, no prior PCI or CABG.

Study Groups:

  • Evolocumab Group: 484 patients received 420 mg of evolocumab subcutaneously.
  • Placebo Group: 484 patients received placebo.

Primary Outcome:

  • Change in Percent Atheroma Volume (PAV) from baseline to week 78:
    • Evolocumab Group: -0.95%
    • Placebo Group: +0.05%
    • Difference: -1.0% (95% Confidence Interval [CI]: -1.8 to -0.64; p < 0.001)

This outcome shows a significant reduction in atheroma volume with evolocumab treatment.

Secondary Outcomes:

  • Change in Normalized Total Atheroma Volume (TAV) (mm³):
    • Evolocumab Group: -5.8 mm³
    • Placebo Group: -0.9 mm³
    • Difference: -4.9 mm³ (95% CI: -7.3 to -2.5; p < 0.001)
  • Plaque Regression for PAV (% of patients showing regression):
    • Evolocumab Group: 64.3%
    • Placebo Group: 47.3%
    • Difference: 17.0% (95% CI: 10.4 to 23.6; p < 0.001)
  • Plaque Regression for TAV (% of patients showing regression):
    • Evolocumab Group: 61.5%
    • Placebo Group: 48.9%
    • Difference: 12.5% (95% CI: 5.9 to 19.2; p < 0.001)

Conclusion:

The GLAGOV trial demonstrates that, among patients with angiographic coronary disease who are already treated with statins, the addition of evolocumab led to a greater reduction in PAV and TAV compared to placebo after 76 weeks. These results provide strong evidence for the efficacy of evolocumab in reducing coronary plaque burden, thus improving the outlook for patients with coronary artery disease.

Reference: Nicholls SJ et al. JAMA. 2016;316(22):2373-2384.

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