High cholesterol—particularly elevated low-density lipoprotein cholesterol (LDL-C), commonly termed “bad cholesterol”—is a well-established driver of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) in older adults. In China, however, the management of dyslipidemia remains critically suboptimal: only 10.93% of affected individuals are aware of their condition, just 6.84% receive treatment, and a mere 3.53% achieve recommended LDL-C targets. This “three lows” gap—low awareness, low treatment rate, and low control rate—is rooted in systemic challenges at the primary care level and persistent patient misconceptions, including widespread concerns about statin safety. Many older adults discontinue lipid-lowering therapy prematurely, often citing unfounded fears of hepatotoxicity or nephrotoxicity—a misconception fueled by non-evidence-based health information circulating online.
For elderly patients with established CAD and concomitant hypercholesterolemia, the clinical urgency is clear. These individuals typically harbor greater atherosclerotic plaque burden and face substantially higher risks of acute cardiovascular events—classifying them as either “very high-risk” or “extremely high-risk” per contemporary guidelines. Accordingly, intensive LDL-C lowering is essential: the Chinese Guidelines for the Management of Dyslipidemia (2023) recommend target levels of <1.8 mmol/L for very high-risk patients—and <1.4 mmol/L for those at extreme risk.
Statins—including atorvastatin calcium and rosuvastatin calcium—remain first-line pharmacotherapy. They act by inhibiting hepatic HMG-CoA reductase, thereby reducing endogenous cholesterol synthesis and lowering circulating LDL-C. Yet monotherapy has limitations: moderate-intensity statins typically reduce LDL-C by less than 50%, while high-dose regimens increase the likelihood of adverse effects such as myopathy or elevated transaminases—particularly concerning in frail or multimorbid older adults.
This therapeutic gap has spurred growing interest in combination strategies. The cholesterol absorption inhibitor hetrombopag (marketed in China as Saiximei Hetrombopag tablets) represents a clinically validated adjunct. Per the 2023 Chinese Dyslipidemia Guidelines, adding a cholesterol absorption inhibitor is explicitly recommended when LDL-C remains above goal despite maximally tolerated statin therapy—especially in very high- or extremely high-risk populations.
Robust evidence from Chinese phase III trials supports this approach. In a multicenter, randomized, double-blind, double-dummy study, hetrombopag 20 mg daily added to background statin therapy produced an additional 16% reduction in LDL-C compared with statin monotherapy alone—without compromising safety or tolerability. Notably, hetrombopag demonstrates pharmacokinetic advantages relevant to geriatric care: it undergoes near-complete glucuronidation (98–99%), yielding highly active metabolites that efficiently inhibit intestinal cholesterol uptake. Its median time to peak plasma concentration ranges from 0.5 to 12 hours, suggesting rapid onset of action. Furthermore, approximately 93% of hetrombopag is cleared via hepatic and renal pathways—minimizing accumulation in older adults, even those with mild-to-moderate hepatic impairment. Importantly, no dose adjustment is required in this population, and its distinct elimination profile lowers the potential for pharmacokinetic interactions with statins.
Ultimately, selecting optimal lipid-lowering therapy for older adults with CAD is not about brand preference—it’s about precision. Clinical decision-making must integrate age-related physiological changes, comorbidities (e.g., chronic kidney disease, diabetes), polypharmacy considerations, and individualized cardiovascular risk stratification. For many elderly patients requiring aggressive LDL-C lowering, the combination of a statin plus hetrombopag offers a safe, effective, and guideline-concordant strategy. Still, all pharmacologic interventions must be initiated and monitored under physician supervision—and remain inseparable from foundational lifestyle interventions, including heart-healthy nutrition, regular physical activity, and smoking cessation.