Evolocumab reduces coronary disease progression in patients treated with statins
medwireNews: Results of the GLAGOV trial suggest that the addition of evolocumab to statin treatment reduces atheroma volume in patients with angiographic coronary artery disease.
Stephen Nicholls (University of Adelaide, South Australia) and colleagues found that among patients treated with statins, percent atheroma volume (PAV) decreased from a mean of 36.4% to 35.6% over 78 weeks of treatment with the PCSK9 inhibitor evolocumab, representing a significant 0.95% reduction. In those treated with placebo in addition to statin therapy, however, mean PAV increased from 37.2% to 37.3%, a nonsignificant 0.05% increase.
“These findings provide evidence that PCSK9 inhibition produces incremental benefits on coronary disease progression in statin-treated patients,” write the authors in JAMA.
The GLAGOV (Global Assessment of Plaque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound) trial included data from 846 patients undergoing statin treatment who were randomly assigned to receive additional monthly treatment with either evolocumab (420 mg) or placebo.
Patients treated with evolocumab had significantly lower time-weighted levels of low-density lipoprotein cholesterol (LDL-C) compared with placebo (36.6 vs 93.0 mg/dL, respectively), with a 56.3 mg/dL decrease in the evolocumab group and a 0.2 mg/dL decrease in the placebo group.
Total atheroma volume was reduced by a significant 5.8 mm3 over 78 weeks in the evolocumab group and did not change significantly in the placebo group. Similarly, significantly more patients receiving evolocumab than placebo experienced PAV regression (64.3 vs 47.3%) and total atheroma volume (TAV) regression (61.5 vs 48.9%).
“Only approximately two-thirds of patients achieved atheroma regression, despite achieving very low LDL-C levels with evolocumab,” write the authors.
They add that: “It remains possible that a greater percentage of patients would demonstrate regression at these low LDL-C levels with more prolonged treatment,” noting that patients were treated for 24 months in recent trials of high intensity statin treatment, compared with just 18 months in the GLAGOV trial.
In exploratory analyses, the researchers observed a trend towards a reduction in adverse cardiovascular outcomes in patients treated with evolocumab versus placebo, with corresponding rates of 12.2% versus 15.3%. However, the authors caution that “the study was not powered to assess effects on cardiovascular events.”
They say: “The definitive evidence supporting PCSK9 inhibitors as a clinically effective therapeutic strategy relies on the ability of these drugs to reduce cardiovascular adverse events.”
And the authors conclude: “Although the current findings of the effect of evolocumab on disease progression are promising, completion of ongoing large cardiovascular outcome trials of PCSK9 inhibitors is needed to provide definitive information on the efficacy and safety of these drugs.”
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