‘Lower and Faster’…Dyslipidemia treatment strategy evolves

Discussion of clinical application of early statin + ezetimibe combination therapy

LDL-C target strengthened… treatment guidelines redefined to below 55 mg/dL

Beyond the question of “how low to lower” LDL cholesterol, “how quickly to reach the target level” is emerging as a key variable in the treatment of dyslipidemia.

As the target has been tightened to below 55 mg/dL, an approach aimed at reaching the goal quickly through initial combination therapy is emerging as an alternative.

According to industry sources on the 21st, treatment strategies for dyslipidemia based on early combination therapy were presented as a major topic at the ACC Asia 2026 Together With KSC Spring Conference held recently in Gyeongju.

Cardiovascular disease is one of the major causes of death in Korea, and dyslipidemia is considered a representative risk factor that can be corrected through treatment.

Nevertheless, the 30-day and 1-year mortality rates of acute myocardial infarction patients in Korea still stand at approximately 9% and 16%, respectively, indicating that existing treatment strategies alone have not been sufficient to adequately reduce early mortality risk. This, together with the fact that the LDL cholesterol target attainment rate in very high-risk patients remains limited, suggests the need for a more aggressive treatment approach.

Against this backdrop, the need for a combination therapy that can overcome the limitations of statin monotherapy has been consistently raised. Notably, the IMPROVE-IT study reported that adding ezetimibe to statins resulted in an additional approximately 24% reduction in LDL-cholesterol, along with a 24% and 32% reduction in the risk of myocardial infarction and ischemic stroke, respectively.

With long-term safety and efficacy subsequently confirmed, ezetimibe has become established in major guidelines as a preferred combination and second-line treatment option.

Professor Jin Wi of the Division of Cardiology at Gachon University Gil Medical Center emphasized the importance of statin + ezetimibe combination therapy at the ACC Asia 2026 Together With KSC Spring Conference.

Professor Jin Wi of the Division of Cardiology at Gachon University Gil Medical Center said, “Dyslipidemia treatment is shifting from a high-intensity statin-centered approach to a more aggressive cholesterol-lowering strategy. It is important to reach LDL cholesterol targets quickly through early combination therapy.”

In particular, he emphasized the importance of dyslipidemia management from a CKM (Cardio-Kidney-Metabolic) perspective, where cardiovascular, kidney, and metabolic diseases are interconnected, saying, “In these patients especially, LDL cholesterol should be controlled aggressively at an early stage.”

He added, “Atorvastatin can be used in chronic kidney disease patients without dose adjustment, which gives it high clinical utility.”

Professor Suk Min Seo, Division of Cardiology at Eunpyeong St. Mary’s Hospital, also noted, “In actual clinical practice, it is difficult to fully implement stepwise therapy due to limitations in patient follow-up. Applying high-intensity statin and ezetimibe combination therapy from the outset is a realistic strategy in terms of achieving the target within a short period and managing risk.”

At the session that day, the ezetimibe/atorvastatin combination product ‘Atozet’ was also introduced as one of the initial combination therapy options.

Beyond ‘lower’ to ‘faster’… guidelines and clinical evidence align

Recent guidelines are demanding changes not only in treatment goals but also in the treatment approach itself.

The 2025 European Society of Cardiology / European Atherosclerosis Society (ESC/EAS) guidelines presented the LDL cholesterol goal for patients with atherosclerotic cardiovascular disease (ASCVD) as below 55 mg/dL and at least a 50% reduction from baseline, and in some very high-risk groups, recommended below 40 mg/dL.

Furthermore, for treatment-naïve ACS patients, the guidelines explicitly recommend considering combination therapy with high-intensity statins and ezetimibe from the outset, emphasizing aggressive intervention at the start of treatment.

The 2026 American College of Cardiology / American Heart Association (ACC/AHA) guidelines likewise presented an LDL cholesterol goal of below 55 mg/dL for very high-risk patients in secondary prevention, and recommend early addition of non-statin agents when the target is difficult to achieve with statin monotherapy alone. Accordingly, the treatment paradigm appears to be shifting from the existing stepwise approach to an early combination-centered strategy.

Professor Suk Min Seo, Division of Cardiology at Eunpyeong St. Mary’s Hospital, presenting at the ACC Asia 2026 Together With KSC Spring Conference

This shift is supported by clinical research. The Ez-PAVE trial was a study designed to verify the clinical validity of lowering the LDL cholesterol target from the conventional 70 mg/dL to 55 mg/dL.

In this study, which enrolled 3,048 Korean ASCVD patients, the group targeting an LDL-cholesterol level below 55 mg/dL achieved a statistically significant reduction of approximately 33% in major adverse cardiovascular events (MACE) over three years compared to the group targeting below 70 mg/dL. This suggests that a strategy of controlling LDL cholesterol to a lower level can lead not only to numerical improvement but also to an actual reduction in clinical events.

Furthermore, the BETTER TRIAL study showed that early combination therapy resulted in significant improvements in both the magnitude of LDL-cholesterol reduction and the rate of target achievement compared to monotherapy. In this study of Korean patients with very high-risk ASCVD, early combination therapy with ezetimibe and atorvastatin, administered before reaching the maximum statin dose, demonstrated significant improvements in both the magnitude of LDL-cholesterol reduction and the rate of target achievement compared to monotherapy.

In particular, the rate of achieving LDL-cholesterol levels below 55 mg/dL was 46.2% versus 9.0% at 6 weeks and 55.0% versus 15.4% at 12 weeks, clearly demonstrating the efficacy of the early combination strategy.

Ultimately, the treatment of dyslipidemia is expanding beyond the question of “how low to lower” to include “how quickly to achieve” the target level. Considering changes in guidelines and clinical evidence, a strategy of applying aggressive combination therapy from the outset is expected to emerge as a key factor in improving patient outcomes.