GLAGOV was a phase 3, multicenter, double-blind, randomized, placebo-controlled study that evaluated the effects of PCSK9 inhibition with evolocumab on top of optimized statin therapy on coronary atherosclerosis progression:
- study compared the change in coronary atheroma volume in patients who received evolocumab with statins to those who received statins alone
- primary efficacy endpoint was the change in percent atheroma volume (PAV) by serial intravascular ultrasonography (IVUS) imaging, performed at baseline and at the end of the 78- week treatment period
- secondary endpoints included the percentage of patients showing PAV regression (any reduction from baseline), change in total atheroma volume (TAV) by IVUS imaging from baseline to 78 weeks, and the percentage of patients showing TAV regression (any reduction from baseline)
- Key inclusion criteria included patients (aged >=18 years) with at least one visual lumen stenosis greater than 20% within a native epicardial coronary artery, reported during a clinically indicated coronary angiogram as an evidence of coronary disease, stable optimized background
statin therapy for ≥ 4 weeks prior to screening and an LDL-C level of >= 80 mg/dL (2.1 mmol/L) or LDL-C >= 60 mg/dL (1.6 mmol/L) but < 80 mg/dL (2.1 mmol/L) in the presence of one major or three minor cardiovascular risk factors- minor cardiovascular risk factors defined for the study were:
- Current cigarette smoking
- Hypertension (blood pressure >= 140/90 mmHg or current use of antihypertensive medications)
- low HDL-C (men, < 40 mg/dL [1 mmol/L]; women,< 50 mg/dL [1.3 mmol/L])
- Family history of premature coronary heart disease
- Age (men, >= 50 years; women, >= 55 years)
- hs-CRP ≥ 2 mg/L
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- patients were excluded if they had uncontrolled diabetes or hypertension, heart failure, renal dysfunction, or liver disease
- patients were randomized 1:1 to receive subcutaneous evolocumab 420 mg monthly or placebo with optimized statin therapy, defined as an effective dose of at least atorvastatin 20 mg daily (or equivalent titrated) to achieve target LDL-C as defined by regional guidelines
- Treatment with statins plus evolocumab achieved mean LDL-C levels of 36.6 mg/dL, produced atheroma regression with a mean change in percent of atheroma volume of about 1% (P < .001), and induced regression in a greater percentage of patients. The clinical benefits of LDL-C were shown as low as 20 mg/dL.
Reference:
Cleve Clin J Med. 2017 Dec;84(12 Suppl 4):e1-e5