Cholesterol Drug Uptake Varies Sharply Across China’s Greater Bay Area

A large real-world study spanning five hospitals in Hong Kong, Macau, Shenzhen and Guangzhou has found that prescribing of PCSK9 inhibitor cholesterol drugs surged in mainland Chinese centers after a national reimbursement policy change, while uptake in Hong Kong and Macau remained comparatively low despite similar clinical benefit wherever the drugs were started. The multi-center cohort study, published in Drugs – Real World Outcomes, analyzed electronic health records from 9,828 adults who began treatment with the injectable lipid-lowering antibodies alirocumab or evolocumab, and it is described by its authors as the largest real-world study of these drugs in Asia.

PCSK9 inhibitors are monoclonal antibodies that dramatically lower low-density lipoprotein cholesterol (LDL-C), the fatty particles that drive atherosclerotic cardiovascular disease. Large randomized trials such as FOURIER and ODYSSEY OUTCOMES established that the drugs reduce LDL-C substantially and cut major adverse cardiovascular events with a favorable safety profile. International guidelines, including those from the European Society of Cardiology and European Atherosclerosis Society, recommend them as an addition to maximally tolerated statin therapy for very-high-risk patients who fail to reach LDL-C targets. Yet the drugs’ high price initially limited adoption after their approval, which came in Hong Kong in 2016 and in Macau and mainland China in 2018.

The pivotal shift came in 2021, when both alirocumab and evolocumab were added to China’s National Reimbursement Drug List at reduced cost. In mainland China the drugs are classified under Category B of that list, meaning patients pay out-of-pocket first and then receive partial government reimbursement, with eligibility restricted to specific clinical indications such as confirmed atherosclerotic cardiovascular disease or familial hypercholesterolemia in patients who have not met LDL-C goals on maximally tolerated statins or who cannot tolerate statins. Hong Kong and Macau operate their own independent formularies. In Hong Kong public hospitals, PCSK9 inhibitors are special drugs available at standard fees only when prescribed by cardiologists or endocrinologists for defined indications; patients outside those criteria must pay roughly HKD 5,000 to 7,000 per month. In Macau, most patients pay the full cost of around MOP 4,000 to 5,000 monthly, although civil servants and people aged 65 and over receive the drugs free through government subsidy programs.

The research team, led by investigators including Celine Sze Ling Chui, Ian Chi Kei Wong and colleagues across the Guangdong-Hong Kong-Macau Greater Bay Area, assembled new users of alirocumab or evolocumab from five data sources: the Hong Kong Hospital Authority, the University of Hong Kong-Shenzhen Hospital, the Macau Health Bureau, Macau University of Science and Technology Hospital, and the First Affiliated Hospital of Jinan University in Guangzhou. Each center contributed records from the date of local drug availability, with study windows running from August 2016 in Hong Kong through December 2024 at the latest cut-off. A common protocol and standardized data dictionary were used, data were analyzed locally at each site, and only aggregated de-identified results were pooled. The cohort included adults aged 18 or older receiving their first-ever recorded prescription for either agent.

The 9,828 new users broke down as 3,768 at the Guangzhou hospital, 3,296 at the Hong Kong Hospital Authority, 2,529 at the Shenzhen hospital, 148 at the Macau Health Bureau and 87 at the Macau private university hospital. Choice of agent differed by center: evolocumab was most commonly prescribed in Hong Kong public hospitals, the Macau private hospital and Guangzhou, while alirocumab predominated in Shenzhen and the Macau public system. The authors attribute these regional differences to divergent institutional drug formularies and procurement agreements rather than clinical distinctions between the two antibodies. Across centers, patients were predominantly older men carrying a heavy burden of atherosclerotic cardiovascular disease, and most were already taking guideline-recommended statins or ezetimibe before starting the injectable therapy, a pattern consistent with the drugs’ intended use as second-line treatment for very-high-risk patients.

Prescribing trends diverged sharply by jurisdiction. In the two mainland centers, the number of new users and the incidence rate of initiation per 10,000 hospital attendances rose steeply after the 2021 reimbursement change. The Guangzhou hospital showed the most pronounced rise, with minimal new users before 2021, a sharp increase from late 2021 onward, and the highest incidence rate of any center, peaking at 23 per 10,000 attendances by 2024. The Shenzhen hospital followed a similar trajectory, rising from mid-2020 and peaking at 13 per 10,000 attendances in 2023 before a modest decline. By contrast, the Hong Kong Hospital Authority, despite an eight-year observation window and a steady absolute increase in new users, kept an incidence rate generally below 1 per 10,000 attendances. The two Macau centers reported very low absolute numbers, reflecting smaller populations and later drug availability, but their attendance-adjusted rates reached 1.7 and 5.1 per 10,000 attendances respectively.

The clinical results were consistent across all five settings. Median LDL-C fell from 2.84 to 1.26 mmol/L in Hong Kong public hospitals, from 2.65 to 1.52 mmol/L in Shenzhen, from 2.92 to 1.28 mmol/L in the Macau public system, from 3.87 to 2.39 mmol/L in the Macau private hospital, and from 2.78 to 1.64 mmol/L in Guangzhou. Median relative reductions ranged from 38 to 56 percent across centers. Roughly 60 to 70 percent of patients achieved the guideline threshold of LDL-C below 1.8 mmol/L at 180 and 365 days after initiation in most centers, with approximately 50 to 60 percent reaching the stricter 1.4 mmol/L target and 30 to 40 percent reaching 1.0 mmol/L in the Hong Kong, Shenzhen and Macau public cohorts. Rates of achieving at least a 50 percent LDL-C reduction ranged from 35 to 67 percent depending on center and follow-up interval. The Guangzhou hospital showed comparatively lower goal attainment than the other centers.

The authors offer several possible explanations for the Guangzhou discrepancy, including incomplete lipid data capture, differences in baseline LDL-C levels, variation in statin intensity and ezetimibe use, and the possibility that patients received follow-up lipid testing at other hospitals outside the study’s data capture. Because the Hong Kong Hospital Authority covers all public hospitals in its territory and the Macau centers span public and private care, data capture in those regions is more comprehensive. The study’s authors also caution that the retrospective design carries inherent limitations: socioeconomic information was missing, comorbidity documentation depended on local coding practices, statin intolerance was not systematically captured, post-initiation statin or ezetimibe use could not be assessed, and medication adherence data were unavailable. The observed LDL-C reductions may therefore reflect intensified background lipid-lowering therapy and variable adherence in combination with the new drugs rather than the effect of PCSK9 inhibitors alone.

The incidence-rate comparisons also carry caveats. Denominators were total hospital attendances, which allow volume-adjusted comparisons but are influenced by institutional differences and by the proportion of attendances from patients who are actually candidates for the therapy, so the rates should be read as approximate indicators of prescribing activity rather than precise population measures. Cross-center comparisons of comorbidity burden should likewise be interpreted with caution. The study periods were not identical across centers, and as clinical experience with the drugs has grown, later periods may reflect expanded prescribing to broader patient groups.

Looking forward, the authors note that new agents may reshape the landscape further. Inclisiran, a long-acting small interfering RNA therapy approved in Hong Kong in 2023 and available as a special drug in the public system and at the Shenzhen hospital, offers less frequent dosing and may compete with or complement the antibodies. In 2024, China’s National Medical Products Administration approved domestically produced PCSK9 inhibitors such as ebronucimab and ongericimab, which are expected to enhance mainland accessibility through competitive pricing, and oral PCSK9-targeting therapy is on the horizon. The updated 2025 European guidelines, which expanded indications to include patients with acute myocardial infarction and acute coronary syndrome and allow clinicians to bypass the traditional stepwise treatment approach, are expected to further increase uptake. The team argues that the findings provide a robust model for multi-jurisdictional evidence generation and that policymakers in Hong Kong and Macau could consider the mainland reimbursement model as a precedent, since broader subsidy schemes or collective drug procurement across the Greater Bay Area might improve equitable access to lipid-lowering therapy. Continuous monitoring of prescribing rates, they conclude, remains essential for identifying gaps in drug initiation across the region’s distinct healthcare systems.

Subject of Research: Real-world utilization and LDL-C goal attainment of PCSK9 inhibitor therapy across five hospitals in the Guangdong-Hong Kong-Macau Greater Bay Area

Article Title: PCSK9 inhibitors usage in South China: A Multi-Center Real-World Study

Article References: Yu, Q., Ma, T., Huang, F., Monteiro, O., Lao, E. P. L., Vong, I. C., Ung, S. I., Li, S., Wu, S., Wang, J., Blais, J. E., Tan, K. C. B., Lui, D. T. W., Yiu, K. H., Wong, I. C. K., & Chui, C. S. L. (2026). PCSK9 inhibitors usage in South China: A Multi-Center Real-World Study. Drugs – Real World Outcomes. https://doi.org/10.1007/s40801-026-00586-2

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00586-2

Keywords: PCSK9 inhibitors, LDL cholesterol, Greater Bay Area, National Reimbursement Drug List, alirocumab, evolocumab, cardiovascular disease, drug reimbursement, real-world evidence, Hong Kong, Macau, hypercholesterolemia