In this real-world effectiveness and safety study of evolocumab in Korea, evolocumab was initiated within 24 weeks of an ACS event in a hospital setting. LDL-C levels were significantly reduced by 50.9% (1.4 mmol/L (55.1 mg/dL) absolute reduction) from evolocumab initiation and 55.1% and 78.7% of patients achieved LDL-C goals of < 1.4 mmol/L (55 mg/dL) and < 1.8 mmol/L (70 mg/dL), respectively, at 8 weeks in the absence of any treatment-related adverse events. These findings fill the gap in the real-world effectiveness of evolocumab among the Asian population, while consolidating the real-world effectiveness of evolocumab in global perspectives and supporting the totality of the evidence combined with the clinical trial results in very high-risk patients with ASCVD.

This study demonstrated the LDL-C-lowering effect of evolocumab among very high-risk patients with ACS in Asia. At the index visit, the median lipid level for the study population was 98 mg/dL, despite that the majority (68.5%) were receiving moderate or high-intensity statin plus ezetimibe. The percentage (50.9%) and absolute (1.4 mmol/L (55.1 mg/dL)) reduction in LDL-C observed in this study at 8 weeks after initiation of evolocumab in patients with post-ACS is comparable with that observed in the large evolocumab outcomes trial, Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) [14]. In patients with established ASCVD in FOURIER, LDL-C was reduced by 59% (absolute reduction 1.6 mmol/L (62 mg/dL)) at 48 weeks. Similar levels of LDL-C reduction have been shown in other real-world studies of evolocumab. In the Canadian cohort (n = 131) of the observational chart review study of evolocumab initiation in patients with ASCVD and/or familial hypercholesterolemia (ZERBINI), after 12 months there was a 59% reduction in LDL-C [18]. In retrospective, observational studies of hospitalized patients with refractory hyperlipidemia and established CVD in Spain (n = 62) [15] and the Czech Republic (n = 108) [16], who received PCSK9 inhibitors (evolocumab or alirocumab) in addition to statins and/or ezetimibe for secondary prevention, LDL-C reductions of 48% (absolute 2.4 mmol/L (92 mg/dL)) and 64% at 6-month and 12-week follow-up, respectively, were shown. Additionally, a retrospective analysis of healthcare claims data in the USA for 152 patients with a recent myocardial infarction (MI) within 12 months prior to evolocumab initiation showed LDL-C levels were lowered by 65% at 12-month follow-up [17]. Notably, in a subgroup analysis of the FOURIER trial, the efficacy and safety of evolocumab was compared between Asian (n = 2723) and other (n = 24,841) patients [20]. Baseline LDL-C levels were marginally lower among Asian than among the other patients (2.3 mmol/L (89 mg/dL) vs 2.4 mmol/L (92 mg/dL)); however, at 48 weeks, compared with placebo, mean percentage (66% vs 58%) and absolute (1.6 mmol/L (61 mg/dL) vs 1.4 mmol/L (55 mg/dL)) reductions in LDL-C with evolocumab were greater in the Asian than in the other patients. The authors of the analysis showed that the differences between Asians and others in LDL-C reductions were despite adjustment for baseline body weight and high-intensity statin use (P interaction < 0.001) [20].

Our study also provides evidence of the real-world effectiveness of evolocumab in meeting guideline-recommended LDL-C goal for very high-risk patients with ACS [7]. Importantly, the stringent LDL-C goal of < 1.4 mmol/L (55 mg/dL) was achieved by 55.1% of patients following evolocumab treatment at index visit, while 78.7% of patients achieved the less stringent 2018 ACC/AHA LDL-C goal, < 1.8 mmol/L (70 mg/dL) [6]. The most recent ESC/EAS LDL-C goal for very high-risk patients [7], < 1.4 mmol/L (55 mg/dL) and ≥ 50% reduction from projected baseline (untreated), was achieved by 55.1% of patients, while 94.4% achieved the LDL-C goal recommended by previous 2016 ESC/EAS cholesterol guidelines [21], < 1.8 mmol/L (70 mg/dL) or ≥ 50% reduction from projected baseline (untreated). Previous clinical evidence demonstrating the benefit of early evolocumab initiation comes from EVOPACS in which evolocumab initiated in-hospital with LLTs in patients with ACS resulted in > 95% of patients achieving LDL-C < 1.8 mmol/L (70 mg/dL) [11]. In the placebo-controlled Evolocumab in Acute Coronary Syndrome (EVACS) study, 81% and 65% of patients treated with evolocumab within 24 h of an ACS event achieved the recommended AHA/ACC (< 1.8 mmol/L (70 mg/dL)) and ESC (< 1.4 mmol/L (55 mg/dL)) goals [22]. By contrast, observational studies show that real-world compliance with guideline-recommended LDL-C goals is low in the USA [23] and across Europe, where < 50% of high/very high-risk primary and secondary prevention patients achieve 2016 LDL-C goals and about 20% achieve the lower 2019 goals [24]. In the real-world study of Desai et al. in the USA that included patients with a recent MI, for this subgroup, 69.7% achieved LDL-C < 1.8 mmol/L (70 mg/dL) at 12-month follow-up [17]. Our real-world study shows that evolocumab treatment in patients with very high-risk ACS in a clinical practice setting in Korea results in a higher rate of patients achieving LDL-C goals than that seen in other real-world studies, and similar to that seen in clinical trials.

In the current real-world study in Korean clinical practice, no drug-related adverse or serious adverse events were reported. The favorable safety profile of evolocumab in this study is generally consistent with that shown in randomized controlled trials [14, 25] and other real-world studies in different regions, including Europe [15, 16], the USA [17], Canada [18], and China [26]. This is an important finding as Korean patients were limited in representation in these trials; hence, this study provides relevant data for Korean clinical practice. The finding that no additional safety concerns were identified in our study is not surprising. Consistent with other real-world studies in which no [18] or a few [27] injection-site reactions were reported, in our study there were none; in FOURIER the incidence was 2.1% [14]. In FOURIER, the incidence of AEs (77.4% and 77.4%) and serious AEs (24.8% and 24.7%) with evolocumab was the same/similar as that seen with placebo [14]. In the subanalysis of data from FOURIER in Asians compared with other patients, there were no significant between-group differences in the incidence of AEs including rhabdomyolysis, hemorrhagic stroke, new-onset diabetes mellitus, or cognitive decline [20].

This is the first real-world study of evolocumab conducted exclusively in Korea to provide a perspective of the effectiveness and safety of evolocumab in the treatment of a very high-risk population with ACS in a real-world clinical setting. Moreover, it used projected baseline (untreated) LDL-C levels according to the extrapolation that was suggested in the most recent 2019 ESC/EAS guidelines to estimate baseline (untreated) LDL-C levels [7]. Finally, this study was a multicenter (10 hospitals), prospective study to mitigate the potential bias which can originate from single-center or retrospective settings. Despite its strengths, several important limitations should be addressed. First, the single LDL-C measurement over 8 weeks limits our ability to assess the long-term efficacy of evolocumab in real-world practice. Second, the observational design, with patients’ self-selection and lack of blinding, introduces the potential for confounding and bias. Third, the study cohort focused on a single country, Korea, and its reliance on reimbursement criteria may limit the generalizability to other populations with different age groups, geographical areas, and risk factors.