Residual cardiovascular risk persists despite LDL-C reduction

Korean cohort study of 70,000 statin users… combination therapy reduces cardiovascular risk by 24%

Residual risk persists after LDL-C control…Need to manage TG, TRL-C

Market expected to expand with the use of pitavastatin-fenofibrate combinations

The treatment paradigm for dyslipidemia is expanding beyond lowering LDL cholesterol (LDL-C) to simultaneously managing triglycerides (TG) and triglyceride-rich lipoprotein cholesterol (TRL-C).

This reflects the growing importance of strategies for managing so-called “residual risk,” as cardiovascular risk may remain even when statin therapy lowers LDL-C below the target level.

Korean cohort study of 67,000 patients confirms benefits of ‘statin+fenofibrate’ combo

According to industry sources on the 31st, the TRIUMPH study, published in the May 2026 issue of the international journal Journal of Lipid Research, analyzed the preventive effects of combined statin and fenofibrate therapy on cardiovascular disease using large-scale real-world data (RWD).

Researchers including Professor Youngwoo Jang and Professor Seung Hwan Han of the Division of Cardiology at Gachon University Gil Medical Center, Professor Byung Jin Kim of Kangbuk Samsung Hospital, and Professor Dae Ryong Kang of Yonsei University conducted a long-term follow-up of 67,662 statin-treated adults without pre-existing cardiovascular disease, using data from the National Health Insurance Service–National Sample Cohort (NHIS-NSC).

The researchers divided the patients into two groups based on a median TRL-C level of 26 mg/dL and performed propensity score matching (PSM) to compare the risk of developing atherosclerotic cardiovascular disease (ASCVD) between those receiving statin-fenofibrate combination therapy and those receiving statin monotherapy.

Over a mean follow-up period of 87 months, adding fenofibrate reduced the risk of ASCVD by 24% compared with statin monotherapy in patients with TRL-C levels of 26 mg/dL or higher. In contrast, the risk reduction was not statistically significant among patients with TRL-C levels below 26 mg/dL.

TRIUMPH study results. AI-generated image

Because previous large-scale clinical trials of fenofibrate, such as the ACCORD-LIPID study, enrolled broad patient populations, they had limitations in demonstrating additional cardiovascular risk reduction with fenofibrate. The latest study, however, stratified patients by TRL-C level. Its significance lies in suggesting that fenofibrate combination therapy may be associated with a meaningful reduction in cardiovascular risk among statin-treated patients with TRL-C levels of 26 mg/dL or higher.

Blocks residual risk after LDL-C control…Need to manage TG and TRL-C highlighted

LDL-C remains a key therapeutic target in the prevention of cardiovascular disease. However, cardiovascular events can still occur even after statin therapy has sufficiently lowered LDL-C. Researchers are consequently paying closer attention to residual cardiovascular risk and to elevated TG and TRL-C levels as major contributing factors.

TRL-C refers to cholesterol contained in remnant lipoproteins generated as triglyceride-rich lipoproteins produced by the liver are broken down. Like LDL-C, it can accumulate in blood vessel walls and contribute to atherosclerosis, and is also known to be associated with local inflammatory responses.

In particular, patients with complex dyslipidemia accompanied by metabolic abnormalities, diabetes, or hypertriglyceridemia may continue to have elevated TG and TRL-C levels even when LDL-C is controlled with statin monotherapy.

Against this backdrop, adding fenofibrate to statin therapy is gaining attention as a treatment option for patients whose TG and TRL-C levels remain elevated.

Fixed-dose combinations draw attention… reduce pill burden and simultaneously manage LDL-C and TG

In practice, the use of fixed-dose combinations is also expanding in consideration of the pill burden and treatment adherence of patients who must take multiple medications over the long term. Pitavastatin-fenofibrate fixed-dose combinations are a prime example.

Pitavastatin lowers LDL-C, while fenofibrate improves the lipid profile mainly by reducing TG. Combining the two active ingredients into a single product enables simultaneous management of LDL-C and TG while improving dosing convenience.

In particular, the TRIUMPH study demonstrated an association between fenofibrate combination therapy and reduced ASCVD risk among statin-treated patients with TRL-C levels of 26 mg/dL or higher. This is expected to heighten interest in treatment strategies that consider not only LDL-C but also TG and TRL-C.

Based on the findings, the industry expects the use of pitavastatin-fenofibrate fixed-dose combinations to expand further on-site.

According to the Ministry of Food and Drug Safety, a total of 39 pitavastatin-fenofibrate fixed-dose combination products have been approved in Korea. Hanlim Pharm became the first Korean company to secure approval for such a combination in 2019 with ‘Stafen Cap,’ followed by a series of generic approvals.