Lipid Lowering Therapy on Coronary Artery Plaque in East Asians

Corresponding Author

Atherosclerotic cardiovascular disease (ASCVD) continues to be a leading cause of morbidity and mortality worldwide, making the control of risk factors like lipid levels a critical aspect of managing cardiovascular health.¹ Among the strategies for mitigating ASCVD risk, lipid-lowering therapy (LLT)—particularly the reduction of low-density lipoprotein cholesterol (LDL-C)—has shown promising results in stabilizing and potentially reversing atherosclerotic plaque.2, 3, 4 Atherosclerosis is not a 1-size-fits-all disease, and emerging data suggest that treatment strategies, especially those targeting LDL-C, need to be adapted based on population-specific characteristics. Although guidelines are mostly applicable in Western populations, because they are largely based on studies conducted in these regions, in the last few years some evidence has also been emerging in the particular context of East Asian populations. East Asians have been shown to have superior statin responsiveness and lower LDL-C levels than their Western counterparts, which could result in different therapeutic needs.^5,6

In this issue of JACC: Asia, Fujisaki et al⁷ offer an invaluable insight into how LLT affects coronary atherosclerotic plaque (CAP) stability and progression specifically in East Asian populations, adding nuance to our understanding of how ethnic differences might influence treatment outcomes.⁷ The study's systematic review and meta-analysis, encompassing 48 studies with over 4,000 patients, underscore a significant finding: the benefits of LLT in East Asian patients. By synthesizing data from multiple studies, the authors found that intensive LLT, particularly when aiming for a more stringent LDL-C target of <55 mg/dL, has a profound impact on both plaque regression and stabilization. The decrease in percent atheroma volume (PAV), a key indicator of plaque regression, was most prominent when LDL-C levels were reduced to the lowest levels in the study, underscoring the importance of aggressive lipid management also in this population. Notably, a reduction in PAV by −1.56% (95% CI: −2.20% to −0.92%) was observed in those with LDL-C levels ≤55 mg/dL, a result that signals significant therapeutic benefits at lower LDL-C levels.

Moreover, the meta-analysis highlights that LLT does more than simply shrink plaques. It also appears to enhance the structural integrity of the fibrous cap, a crucial component of atherosclerotic plaques that helps to prevent plaque rupture and the subsequent risk of heart attack. In the East Asian cohort, LLT was associated with an increase in fibrous cap thickness by 66.90 μm (95% CI: 50.06-83.75 μm), suggesting a stabilizing effect on vulnerable plaques. The study also observed a trend that lower LDL-C levels during follow-up were associated with larger increases in fibrous cap thickness, which could point to the possibility of reducing the risk of acute coronary events. Once again, the lower the better.

A previous meta-analysis have explored the specific effects of LLT in East Asian populations, especially examining the impact of LLT on coronary plaque burden and concluding that there was a different effect of LDL-C lowering on CAP between Westerns and Asians.⁸ For regressing CAP, Asians need lower dosage of statins or lower-intensity LDL-C–lowering therapy than Western patients. Nevertheless, this must not be interpreted as an indication for the down-titration of LLT in this population; the findings of the study by Fujisaki et al⁷ underline the importance of reaching LDL-C levels ≤55 mg/dL also in this population because the lowest level of follow-up LDL-C (≤55 mg/dL) was associated with the greatest decrease of PAV when compared with ranges >70 mg/dL. This data aligns with the guidelines that advocate for aggressive lipid-lowering therapy in high-risk patients but highlights that East Asians may benefit from even more intensive treatment compared with what is currently done in clinical practice for them.

Furthermore, there is evidence to suggest that nonstatin therapies, such as PCSK9 inhibitors and ezetimibe, may be particularly effective in East Asian populations.⁹ The use of these therapies could play an important role in achieving the aggressive LDL-C targets now recommended in high-risk East Asian patients.

In summary, the study by Fujisaki et al⁷ presents robust evidence that LLT, particularly with more stringent LDL-C targets, significantly improves atherosclerotic plaque stability and reduces plaque progression in East Asian patients with ASCVD or who are at high risk for it. The results reinforce the growing body of evidence supporting the benefits of intensive lipid-lowering strategies and advocate for the consideration of lower LDL-C targets in clinical practice even in this population. Given the rising burden of ASCVD in East Asia, this study serves as a timely reminder that personalized and aggressive lipid management could play a pivotal role in reducing cardiovascular events and improving long-term outcomes.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.