Article Impact Level: HIGH Data Quality: STRONG Summary of Circulation, 0(0). https://doi.org/10.1161/CIRCULATIONAHA.122.061620 Dr. Michelle O’Donoghue et al
Points
- The study’s main goal was to find out the cardiovascular disease risk effect reduced with PCSK 9 inhibitor evolocumab and lower LDL-C.
- The results of this study also indicated that evolocumab is safe and effective for a median of 2.2 years in parent study and long-term for a median of 5 years and maximum up to a median of 8 years during parent FOURIER and FOURIER-OLE trials.
- The findings of this study also suggest that large-scale and long-term data is missing, which is a prerequisite to evaluating its safety
Summary
In FOURIER, the use of evolocumab, which is a PCSK9 inhibitor and reduced the level of LDL-C, ultimately reducing the risk of cardiovascular disease. The parent FOURIER trial included 27564 patients with atherosclerosis cardiovascular disease (ASCVD) with a level of LDL-C ≥ 70 mg/dl on a statin to evolocumab versus placebo. Parent FOURIER patients were further involved in FOURIER-OLE, which receives evolocumab in the United States and Europe. Levels of LDL-C and adverse reactions to cardiovascular disease were collected.
FOURIER-OLE included 6,635 patients, out of which 3355 were exposed to evolocumab, whereas for placebo, 3280 patients were included with a median follow-up of 5 years. Moreover, Median LDL-C (30mg/dl) was obtained after 12 weeks, and LDL-C < 40 mg/dl, which is about 63.2% obtained on evolocumab. Severe adverse effects with evolocumab do not exceed long term as well as later on, which include muscle-related, new-onset diabetes, neurocognitive and hemorrhagic stroke compared with placebo-treated patients.
Results from patients in the trial parent to evolocumab versus placebo during the FOURIER-OLE trial showed that a lower risk for cardiovascular death was found at 15%, 20%, and 23%, respectively. During this FOURIER-OLE trial, the 15% and 20% lower risks were also found for MI and stroke. It is concluded that low rates of adverse reactions were found as long-term LDL-C was lowered using evolocumab for over eight years compared to placebo during the initial parent study. This also leads to lowering cardiovascular effects when compared with delayed initiation of treatment.
Link to the article: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061620
References O’Donoghue, M. L., Giugliano, R. P., Wiviott, S. D., Atar, D., Keech, A. C., Kuder, J. F., Im, K., Murphy, S. A., Flores-Arredondo, J. H., Lopez, J. A. G., Elliott-Davey, M., Wang, B., Monsalvo, M. L., Abbasi, S., & Sabatine, M. S. (n.d.). Long-term evolocumab in patients with established atherosclerotic cardiovascular disease. Circulation, 0(0). https://doi.org/10.1161/CIRCULATIONAHA.122.061620
