Adding evolocumab to high-intensity statins in ACS patients reduces LDL-C substantially

The Swiss EVOPACS study showed that the PCSK9 antibody evolocumab added to high-intensity statin therapy in the very high-risk acute setting of acute coronary syndrome (ACS) resulted in a substantial reduction in LDL-C levels in patients. Treatment was safe, well tolerated, and raised no safety concerns.

Lowering low-density lipoprotein (LDL)-C levels by treating ACS patients in the acute phase with high-intensity statins results in early (within 30 days) clinical benefit [1,2]. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have also shown to lead to rapid, profound LDL-C reduction in patients without atherosclerotic cardiovascular disease (CV) or with stable/stabilised coronary artery disease (CAD) [3,4]. Dr Konstantinos Koskinas (Bern University Hospital, Switzerland) and colleagues set up the first randomised trial assessing the PCSK9 antibody evolocumab in the very high-risk acute setting of ACS.

A total of 308 patients with similar baseline characteristics were included (evolocumab SC 420 mg + atorvastatin 40 mg once daily: n=155 and placebo SC + atorvastatin 40 mg once daily: n=153). Study duration was 8 weeks. Primary endpoint was the percentage change in LDL-C from baseline to 8 weeks, with safety and tolerability as secondary endpoints. Those who received evolocumab achieved average LDL-C levels of 0.79 mmol/L vs 2.06 mmol/L with statin alone. Also, >90% of patients (vs 11% of those receiving placebo) achieved currently recommended target levels. Treatment was safe and well tolerated and did not result in measurable differences in surrogate outcomes such as inflammatory biomarkers, platelet reactivity, acute kidney injury, and myocardial injury.

Dr Koskinas pointed out that the study did have some limitations: “It was not powered to assess clinical outcomes. Secondly, although 95% of patients completed the final (week 8) clinical visit, the primary endpoint (i.e. change in calculated LDL-C) was available in 90% of patients only (94% for directly measured LDL-C). Finally, because lipid levels were measured 4 weeks after the first study drug administration, earlier effects of evolocumab could not be assessed. Nevertheless, the outcomes of this study are promising and require further research in a dedicated CV trial [5].”

1. Ray KK, et al. [JACC. 2005;46:1405-10](https://www.ncbi.nlm.nih.gov/pubmed/16226162).
2. Schwartz GG, et al. [JAMA. 2001;285:1711-8](https://www.ncbi.nlm.nih.gov/pubmed/11277825).
3. Sabatine MS, et al. [NEJM. 2017;376:1713-22](https://www.nejm.org/doi/10.1056/NEJMoa1615664).
4. Schwartz GG, et al. [NEJM. 2018;379:2097-107](https://www.nejm.org/doi/full/10.1056/NEJMoa1801174).
5. Koskinas K, et al. Evolocumab for Early Reduction of LDL-Cholesterol Levels in Patients with Acute Coronary Syndromes. FP Number 82. ESC Congress 2019, 31 Aug-4 Sept, Paris, France.



Posted on 10 October 2019