The use and efficacy of statins in Hong Kong Chinese dyslipidaemic patients in a primary care setting

Kenny Kung 龔敬樂，Augustine Lam 林璨，Philip K T Li 李錦滔

HK Pract 2005;27:450-454

Summary

Objective: To evaluate the use and efficacy of lipid-lowering drugs in the Hong Kong primary care setting, comparing with data from international controlled trials.

Design: Retrospective analysis of pre- and post- treatment lipid levels amongst a cohort of patients with dyslipidaemia.

Subjects: All patients with dyslipidaemia attending our Family Medicine Training Centres during the period from 1st July 2003 to 31st October 2003.

Main outcome measures: Pre- and post- treatment serum lipid levels (including total cholesterol, high and low density lipoproteins, and triglycerides).

Results: 2762 patients with dyslipidaemia were seen during the stated time period. 41.9% were not on any lipid-lowering drugs, 48.3% were on statins, 9.3% were on gemfibrozil. There were significant differences in drug prescriptions in the >90 years of age group as compared with all other age groups, irrespective of the type of drug used. Lipid levels were achieved at lower doses of statin in comparison to previous trial data.

Conclusion: Lower doses of statin in comparison to international trials can be used to achieve the same level of LDL reduction in our local population, thereby reducing costs and possible side-effects. Further prospective studies at the general population level can be performed to elucidate this difference in dose requirements.

Keywords: Statin, dyslipidaemia, lipid, Hong Kong Chinese, primary care

摘要

目的： 評估香港基層醫療降脂藥物的使用情況和效能，並與國際對照性試驗的結果進行比較。

設計： 對高血脂症病人，用藥前後的血脂濃度做回顧性分析。

研究對象： 二零零三年七月一日至二零零三年十月三十一日，所有到家庭醫學訓練中心覆診的高血脂症病人。

主要測量內容： 治療前後的血脂濃度(包括總膽固醇、高密度和低密度脂蛋白，甘油三酯)。

結果： 分析期間共有2762名血脂過高的病人，41.9%的病人未使用脂質降低藥物， 48.3%使用他汀，9.3%使用吉非 貝齊。不論是何類型的降脂藥物，九十歲或以上的病人和其他年齡組別的處方都有明顯的差別。 比較以往的試驗數據，較低份量的他汀可達到降低血脂的目的。

結論： 比較國際性的試驗結果，本地病人可用較低份量他汀達至同樣的效果，醫療費用和副作用都會較少。可以進行一 些有關藥物份量差異的前贍性研究。

詞彙： 他汀，血脂異常，血脂，中國人，基層醫療。

Introduction

Although dyslipidaemia comprises only a small percentage of patients in Hong Kong's general practice (0.5% in private practice, 0.3% in general outpatient),¹ it nevertheless is important because of its inherent risks for cardiovascular disease. Indeed, 17.9% of the elderly population (>60 years old) have high cholesterol levels.² Additionally, heart diseases were the second commonest cause of death in Hong Kong (14.5%).³

The management of dyslipidaemia, and more importantly the use of statins in management have been well-established.⁴ Statins are the most powerful agents for reducing low density lipoprotein (LDL) levels (in the range of 20-60%⁵). Their effect on Chinese populations was recently investigated in Singapore⁶. This showed that doses similar to those in Western populations were required in order to achieve a similar cardiovascular risk reduction. This is despite an obvious difference in body build and genetic background between the two ethnic groups. However, Hong Kong Chinese are different and unique in that their genetic background is mixed with a westernized culture. It is uncertain whether the Singaporean data and indeed previous overseas data could be applied to our population.

Although lipid-lowering therapy is known to be effective, translating clinical trials evidence to primary care general practice management is often difficult. Compliance is a very important issue. In a retrospective cohort study performed in primary care general practice setting,⁷ the one-year discontinuation rate was substantially higher than in clinical trials, ranging from 15% for statins and 37% for fibrates. The discrepancies between the discontinuation rates in clinical trials versus the primary care setting have reduce the benefits shown of lipid-lowering therapy and the cost-effectiveness that have been predicted from controlled trials.

This study aims to review the current management of dyslipidaemia in primary care, as well as looking at the efficacy of statins in the Hong Kong Chinese population.

Method

Computer data from patients with dyslipidaemia who attended the Family Medicine Training Centre (FMTC) at the Prince of Wales Hospital or Fanling Family Medicine Centre (FLFMC) during the period from 1^st July 2003 to 31^st October 2003 were retrieved. Blood results and drug-use information within the computer management system from the time these dyslipidaemic patients started attending these clinics (dating back to July 1999) were obtained. All patients identified to have dyslipidaemia through International Classification of Primary Care coding (disorders of lipid metabolism, T93) were included in the initial data analysis, which also include the collection of the following data:

1. Patient demographics
2. Type of lipid lowering drug used

Exclusions were made of those who fall under the following criteria:

1. Patients seen for the first time at our clinics during the review period
2. If the laboratory data dating back to the initiation of their medications were not available in the computer system

Lipid levels (TC, HDL, TG and LDL) before and six months after starting statin therapy were collected from those patients not excluded. P-values for comparing differences in patient subgroups were obtained using chi-square tests. 95% confidence intervals for drug efficacies were calculated through obtaining the standard deviations of the subgroup data points.

Results

2762 patients with dyslipidaemia were identified during the review period, with 1633 females and 1129 males. Among the review population, 41.9% were not prescribed lipid-lowering drugs during the review period. 9.3% were prescribed gemfibrozil, whilst a total of 48.3% were given statin therapy (Figure 1).

The age distribution amongst those taking and those not taking any medications is shown in (Figure 2). The over 90 years old age group were significantly less likely to receive any lipid lowering drugs (P<0.001) when compared to all other age groups (Figure 3).

The efficacy of simvastatin, atorvastatin and fluvastatin treatment on TC, HDL, TG and LDL levels as well as TC:HDL ratio is shown in (Figures 4-8) respectively, and summarized in Table 1. The efficacy of statins from previous trial data⁸ is compared with that from this review in Table 2.

Discussion

9Data from this review reinforced the adequacy of statins in reducing LDL levels and TC:HDL ratios, thus reducing patients' cardiovascular risks. However, their effect on HDL and TG was small. Indeed, only simvastatin resulted in significant changes. Simvastatin and atorvastatin at 20mg achieved changes in LDL, TG and HDL that were comparable to their 40mg dosing effects noted from current literature. This suggests that smaller doses can be used to achieve the same level of reduction. This is in contrast to a recent study in Singapore which suggested that Asians should receive the same high doses as that in trials.⁶ Chinese and other Asians have lower body mass indices as compared with Western counterparts. Moreover, differences in genetic makeup can also influence the pharmacokinetic properties of statins.^9,10 Combining these presumptions, lower statin doses for achieving the same lipid levels are indeed plausible in Chinese patients.

It was not possible to control lifestyle factors and drug compliance in this retrospective review. However, despite these possible confounders it seems that in our population the combined approach of lipid-lowering drug therapy and lifestyle advice was effective in reaching lipid levels achieved under controlled trial conditions. This is both reassuring and important to our daily practice since it is presumably difficult to reinforce drug trial requirements in a general practice setting. More importantly, while previous studies cast doubts on trial results because of lower compliance in general practice,⁷ this has not appeared to affect their efficacy.

This review is limited by its retrospective nature and population selection bias. Our population was heterogeneous in nature, including patients with many different indications for lipid lowering therapy. Only patients attending the two training centres were included for review, potentially selecting only those at higher risks than the general population. Future directions will need to include data of patients from general outpatient clinics, and relating lipid lowering effects to clinical outcome in general practice.

Conclusion

This review on the management of dyslipidaemia in Hong Kong primary care setting has confirmed the applicability of overseas data to our local population. Furthermore, there is current indication that perhaps lower doses of medications should be used, thus reducing costs and possible side-effects. With hospital clustering and development of the computer management system across general outpatient clinics, further prospective studies at the general population level can be performed to investigate prescribing patterns and cost-effectiveness relating to mortality and morbidity.

Key messages

1. 17.9% of the Hong Kong elderly population have dyslipidaemia.
2. Statins are effective in reducing LDL levels in the Chinese population; however, doses lower than previous international trial data may be adequate in achieving the same lipid lowering levels in our population.