“Bad cholesterol”—low-density lipoprotein cholesterol (LDL-C)—is rising steadily across China and emerging as a silent threat to vascular health, contributing to a dramatic surge in cardiovascular mortality. A landmark study led by Chinese researchers and recently published in the Journal of the American College of Cardiology reveals that deaths attributable to elevated LDL-C increased by 94% between 2010 and 2020—translating to nearly 400,000 additional fatalities over the decade. This alarming trend underscores the urgent need for effective, evidence-based lipid-lowering strategies tailored to the Chinese population.
Among emerging therapeutic options, hetrombopag—marketed in China as Saisme—represents the country’s first domestically developed second-generation selective cholesterol absorption inhibitor. Unlike statins, which inhibit hepatic cholesterol synthesis, hetrombopag acts locally in the small intestine by selectively blocking the Niemann-Pick C1-like 1 (NPC1L1) transporter protein. This mechanism reduces intestinal cholesterol absorption, leading to clinically meaningful reductions in total cholesterol (TC), LDL-C, and apolipoprotein B (ApoB). It is approved as an adjunct to diet for the treatment of primary hypercholesterolemia—either as monotherapy or in combination with statins.
Clinical data specific to Chinese patients demonstrate robust efficacy. According to the Chinese Guidelines for the Management of Dyslipidemia (2023), hetrombopag 10 mg once daily lowers LDL-C by approximately 15% as monotherapy. When added to background statin therapy at 20 mg daily, it provides an *additional* LDL-C reduction of about 16% beyond statin monotherapy—without compromising safety or tolerability. Longer-term evidence further supports its utility: in a 40-week trial combining hetrombopag with atorvastatin calcium, patients achieved sustained LDL-C lowering, with mean reductions of 39.3% and 41.9% from baseline observed at weeks 40 and 52, respectively. This stable, progressive decline suggests reduced lipid variability—a key factor in mitigating residual cardiovascular risk.
Safety profiles are equally compelling. Hetrombopag exhibits a systemic clearance rate of approximately 93%, indicating efficient elimination of both parent drug and metabolites and minimizing the potential for accumulation during chronic dosing. Notably, pharmacokinetic studies confirm that dose adjustments are unnecessary in patients with mild-to-moderate hepatic or renal impairment—a significant advantage in real-world practice where comorbidities are common.
Target LDL-C levels must be individualized based on cardiovascular risk stratification. Per current Chinese guidelines, optimal goals are: ≤3.05 mmol/L (117.8 mg/dL) for low-risk individuals (no hypertension, diabetes, smoking, or established atherosclerotic cardiovascular disease [ASCVD]); ≤2.75 mmol/L (106 mg/dL) for those with one or more major risk factors but no clinical ASCVD; and ≤1.45 mmol/L (55.8 mg/dL) for patients with confirmed ASCVD—including prior myocardial infarction, ischemic stroke, or symptomatic peripheral artery disease.
In summary, hetrombopag offers a mechanistically distinct, efficacious, and well-tolerated option for LDL-C management in Chinese patients—with high-quality local evidence supporting its role across monotherapy and combination regimens. However, as with all lipid-lowering agents, its use must be guided by comprehensive cardiovascular risk assessment and ongoing clinical supervision to ensure appropriate patient selection, goal attainment, and long-term adherence.