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. 2017 May 17;7(5):e014150. doi: 10.1136/bmjopen-2016-014150

10-year trends in statin utilization in Taiwan: a retrospective study using Taiwan’s National Health Insurance Research Database

Hsing-Chun Hsieh 1,2, Jason C Hsu 1, Christine Y Lu 3
PMCID: PMC5541294  PMID: 28515189

Abstract

Objective

Statins have been commonly used to treat patients with hypercholesterolaemia and to prevent cardiovascular disease (CVD) worldwide. This study examined trends in use of statins in Taiwan from 2002 to 2011.

Design

This is a retrospective observational study focusing on the utilisation of statins.

Setting

The monthly claims data for statins between 2002 and 2011 were retrieved from Taiwan’s National Health Insurance Research Database.

Main outcome measures

We calculated the yearly prescription rate per new user for each statin. Products were classified as high-intensity/moderate-intensity/low-intensity statins by type of statin and dosage. Users were also classified based on disease histories.

Results

The number of statin users increased from 10 299 (~1.4% of adults) in 2002 to 50 687 (~6.3% of adults) in 2011. Atorvastatin was the most commonly used agent (28.4%–36.7%) during the study period. After 2007, simvastatin ranked second with 21.7% market share, followed by rosuvastatin, a newer agent that exhibited a substantial growth in prescription rates (3.4% in 2005 and 19.5% in 2011). In 2011, 94.0% of new statin users used statin monotherapies, and 6.0% used combination therapies. Use of moderate-intensity statins increased from 49.0% in 2002 to 71.0% in 2011, while high-intensity statins remained low. Patients with history of coronary events or cerebrovascular events were more likely to be prescribed higher intensity statins compared with those without. Prescribing of higher intensity statins was not greater among people with diabetes compared with those without during 2007–2011. Selection of statins did not differ between people with versus without history of myopathy or liver injury.

Conclusion

Atorvastatin was the most commonly used statin in Taiwan during 2002–2011. While patients with history of CVD were more likely to be prescribed higher intensity statins compared with those without, this difference was not found comparing those with and without diabetes.

Keywords: Statins, Drug utilization, Prescription pattern, Taiwan

Strengths and limitations of this study.

  • This is the first study to investigate 2002–2011 trends in prescribing patterns of statins among new statin users in Taiwan.

  • Data were retrieved from Taiwan’s National Health Insurance Research Database with nearly 99% of the Taiwanese population (around 23 million residents) enrolled and 97% of hospitals and clinics throughout the country.

  • While patients with history of cardiovascular disease were more likely to be prescribed higher intensity statins compared with those without, this difference was not found comparing those with and without diabetes. Appropriateness of statin use among diabetes needs further investigation.

Introduction

Coronary heart disease accounts for approximately one-third of global deaths in recent years.1 Similarly, cardiovascular diseases (CVD) are leading causes of death in Taiwan.2 Low-density lipoprotein cholesterol (LDL-C) has been identified as one of the major modifiable risk factors of CVD.3–6 Fundamental lifestyle changes and several medications have been recommended to control blood cholesterol. Among all medicines, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are a major drug class given their efficacy in reducing LDL-C.7–9 On average, administration of statins helps to lower LDL-C by 20% to 60%.6 10–12 In addition to lowering cholesterol, statins are shown to decrease risk of coronary events by 18%, myocardial infarction by 24% and heart failure by 35%.13

Statins are recommended by major clinical guidelines as the drug of choice for reduction of blood lipids to prevent CVD globally.7–9 In the USA, the 2013 ‘American College of Cardiology/American Heart Association (ACC/AHA)’ Guideline7 recommends that patients with CVD history or with CVD risk factors, such as high LDL-C and diabetes, receive moderate-to-high-intensity statins.7 The European Society of Cardiology (ESC) and UK’s National Institute for Health and Care Excellence guidelines suggest prescribing statins with the highest recommended dose in order to reach target cholesterol level.8 9 In Taiwan, prescribing of statins generally follows drug coverage requirements under the National Health Insurance (NHI), which recommends the use of statins in patients with CVD risk factors or with high cholesterol level.14 It is reasonable for patients to be prescribed with a statin plus another lipid-lowering agent if triglyceride level is also high.

Statins have been the most commonly prescribed drugs in the world in recent decades; their global market sales reached around $28.5 billion in 2014.15 16 Previous studies from the USA and Europe showed substantial increases in statin users, prescription rates and prescribed daily doses of statins over time.17–19 Likewise in Taiwan statin users grew from 190 000 in 2000 to nearly 600 000 in 2004, and drug expenditures and prescription doses escalated over 200% and 400%, respectively.20 21 Based on the updated clinical guidelines and related evidence, use of the more intense statin therapy for secondary prevention and initiation of statins for primary prevention among patients who are at a higher risk of CVD has increased.7 22

While statins have been the mainstay of cholesterol control and heart attack and stroke prevention for the past 20 years, the treatment paradigm may change with the availability of new drugs that target an enzyme called PCSK9 (PCSK9 inhibitors) in 2015.23 However, little is known about recent statin use in Taiwan.24 The aims of this study were to examine the prescribing patterns of statins over the last decade and to investigate the association between patients’ medical history and drug selection of statin. Our study results can be used to improve rational use of statins in light of clinical recommendations. At present, PCSK9 inhibitors are not yet reimbursed by Taiwan’s National Health Insurance (NHI). Our findings also provide baseline trends that can be used to examine how new PCSK9 inhibitors, once become available under the NHI, impact the market of cholesterol medications.

Methods

This study used claims data from the 2010 Longitudinal Health Insurance Database (LHID2010) derived from Taiwan’s National Health Insurance Research Database (NHIRD), which compiles data of over 99% of people (around 23 million residents) in Taiwan.25 LHID2010 contains all the original claims data of 1 million beneficiaries randomly sampled in year 2010 from the NHIRD. LHID2010 data are overall representative of all beneficiaries as no significant differences were found in the distributions of age, gender and average premium rate between individuals in the LHID2010 and the original NHIRD data sets.26 The data set provides information on demographic characteristics, diseases diagnosis, treatment and related medical expenditures, and orders of ambulatory and inpatient care.

New statin users in each year during 2002–2011 were included and formed the study population of each year. New statin users were defined as those who had not taken any statin in the previous years prior to the index date. The index date of every patient in each study year was defined as the date of the first statin prescription in the year. For patients in every study year, only the first prescription that contained any statins was examined in this study. We used the Anatomical Therapeutic Chemical (ATC) codes27 to identify patients who were prescribed any statins, including atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin. Monotherapy was defined as only one statin prescription on the index date, while combination therapy was defined by prescriptions for a statin plus other lipid-lowering drugs (such as fibrates) on the index date.

The main measure was yearly prescription rate of each statin among new statin users. Yearly prescription rate of a specific statin agent was calculated by the number of patients prescribed with the specific statin agent divided by the total number of new statin users in the year. We also calculated the yearly prescription rates of monotherapy/combined statin therapy and of different levels of intensity.

Statins were grouped into three levels of intensity according to their ability to lower LDL-C based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol7 and Rosenson et al 28: (1) high-intensity statins: atorvastatin ≧40 mg/day, rosuvastatin ≧20 mg/day and simvastatin ≧80 mg/day; (2) moderate-intensity statins: 10 mg/day ≦ atorvastatin <40 mg/day, 5 mg/day ≦ rosuvastatin <20 mg/day, 20 mg/day ≦ simvastatin <80 mg/day, pravastatin ≧ 40 mg/day, lovastatin ≧40 mg/day and fluvastatin ≧80 mg/day; and (3) low-intensity statins: atorvastatin <10 mg/day, rosuvastatin <5 mg/day, simvastatin <20 mg/day, pravastatin <40 mg/day, lovastatin <40 mg/day and fluvastatin <80 mg/day. Daily dose can be calculated from the information of what statin has been prescribed, its dosage form, frequency and number of pills within a certain period.

All new statin users were also classified based on whether they have disease histories of interest (including coronary events, cerebrovascular events, myopathy, liver injury and diabetes) or not. Disease histories were identified by the International Classification of Diseases, 9th edition diagnosis codes for major coronary artery disease (410, 411), major cerebrovascular (430, 431, 433–436), diabetes (250),29 myopathy (792.1, 359.4, 359.8, 359.9) and liver injury (155.0, 155.1, 155.2, 197.7, 230.8, 570, 571.1, 572.2, 572.4, 572.8, 573.3, 573.8, 573.9, 574.0, 574.1, 574.9, 646.7).30 The first three diagnoses relate to use of statin for CVD prevention and the latter two diagnoses related to the potential adverse effects of statins. We anticipate a higher percentage use of higher intensity statins among patients with CVD or diabetes. Myopathy31 32 and liver toxicity32 33 (increasing the enzymes aspartate transaminase and alanine transaminase) are two of the main dose-dependent side effects associated with statin use.34 35 Therefore, it was anticipated that a higher percentage of patients with a history of these diseases would use low-intensity statins. Individuals were defined as having a history of the following diseases if they have a diagnosis within certain years prior to the given year: coronary event (3 years), cerebrovascular event (5 years), diabetes (1 year), myopathy (3 years) and liver injury (3 years).30 36–38

This study applied descriptive statistics to report the prescription rates of each statin and used χ2 test to investigate the associations between patients’ disease history and statin drug selection. All analyses were carried out with SAS V.9.3 software and Excel 2013.

Results

In 2002, 10 299 (~1.4% of adults aged 18 and over) statin users were identified among the 1 million cohort from LHID2010 dataset (table 1). Among statin users, more than half (n=5956; 57.8%) were new users. Statins users grew from 10 299 (~1.4% of adults) in 2002 to 50 687 (~6.3% of adults) in 2011, while the proportion of new statin users declined from 57.8% to 35.0%. More women used statins than men (52.3% vs 47.7% in 2011). The average age of new statin users remained steady (58–60 years old) during the study period. Three quarters of new statin users were diagnosed with dyslipidemia. Hypertension accounted for the highest proportion of comorbidities (60.9% in 2011), followed by diabetes (35.3% in 2011); their rates remained steady during the study period. On the contrary, the proportions of other comorbidities, including ischaemic heart disease and chronic liver diseases, slightly declined over time.

Table 1.

Characteristics of new statin users over time

Year 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Number of new statin users 5956 57.8% 9056 57.6% 10 924 52.4% 10 253 45.9% 12 178 47.0% 13 535 44.4% 15 233 42.7% 16 499 40.3% 17 509 37.8% 17 755 35.0%
All statin users 10 299 100.0% 15 724 100.0% 20 848 100.0% 22 317 100.0% 25 924 100.0% 30 491 100.0% 35 674 100.0% 40 989 100.0% 46 323 100.0% 50 687 100.0%
Sex:
  F 3232 54.3% 4925 54.4% 5913 54.1% 5523 53.9% 6391 52.5% 7180 53.0% 8043 52.8% 8519 51.6% 9185 52.5% 9278 52.3%
 M 2724 45.7% 4131 45.6% 5011 45.9% 4730 46.1% 5787 47.5% 6355 47.0% 7190 47.2% 7980 48.4% 8324 47.5% 8477 47.7%
 Age: mean (SD) 58.41 (11.84) 58.22 (12.19) 57.98 (12.40) 58.44 (12.45) 59.01 (12.51) 59.13 (12.45) 59.35 (12.59) 59.28 (12.68) 59.77 (12.73) 59.76 (12.70)
Indication and comorbidities
 Dyslipidemia (indication) 4457 74.8% 6815 75.3% 8357 76.5% 7844 76.5% 9352 76.8% 10 281 76.0% 11 594 76.1% 12 655 76.7% 13 431 76.7% 13 723 77.3%
 Hypertension 3564 59.8% 5214 57.6% 6192 56.7% 6005 58.6% 7290 59.9% 8031 59.3% 9122 59.9% 9859 59.8% 10 726 61.3% 10 816 60.9%
 Diabetes 2092 35.1% 3168 35.0% 3632 33.2% 3639 35.5% 4336 35.6% 4897 36.2% 5378 35.3% 6011 36.4% 6412 36.6% 6262 35.3%
 IHD 1561 26.2% 2266 25.0% 2530 23.2% 2431 23.7% 2851 23.4% 3078 22.7% 3357 22.0% 3513 21.3% 3680 21.0% 3536 19.9%
 Heart failure 217 3.6% 326 3.6% 367 3.4% 384 3.7% 462 3.8% 486 3.6% 562 3.7% 590 3.6% 644 3.7% 637 3.6%
 Afib 36 0.6% 69 0.8% 74 0.7% 91 0.9% 120 1.0% 141 1.0% 173 1.1% 220 1.3% 188 1.1% 239 1.3%
 CeVD 749 12.6% 1121 12.4% 1245 11.4% 1216 11.9% 1472 12.1% 1626 12.0% 1822 12.0% 1879 11.4% 2090 11.9% 2019 11.4%
 PVD 228 3.8% 344 3.8% 414 3.8% 377 3.7% 478 3.9% 455 3.4% 566 3.7% 591 3.6% 671 3.8% 654 3.7%
 CKD 384 6.4% 497 5.5% 540 4.9% 521 5.1% 608 5.0% 689 5.1% 777 5.1% 839 5.1% 878 5.0% 1027 5.8%
 CLD 1301 21.8% 1867 20.6% 2107 19.3% 1984 19.4% 2142 17.6% 2288 16.9% 2409 15.8% 2585 15.7% 2758 15.8% 2689 15.1%
 COPD 576 9.7% 817 9.0% 977 8.9% 871 8.5% 919 7.5% 996 7.4% 1017 6.7% 1106 6.7% 1141 6.5% 1065 6.0%
 Dementia 49 0.8% 72 0.8% 82 0.8% 83 0.8% 110 0.9% 158 1.2% 199 1.3% 226 1.4% 315 1.8% 298 1.7%
 Malignancy 165 2.8% 255 2.8% 325 3.0% 305 3.0% 397 3.3% 479 3.5% 546 3.6% 655 4.0% 702 4.0% 752 4.2%
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Unit: number of patient.

Afib, atrial fibrillation; CeVD, cerebrovascular diseases; CKD, chronic kidney diseases; CLD, chronic liver diseases; COPD, chronic obstructive pulmonary disease; IHD, ischaemic heart disease; PVD, peripheral vascular diseases.

Table 2 presents the statin choices among new statin users. Atorvastatin was the most commonly prescribed statin among new statin users throughout the study (33.8% in 2002 and 35.8% in 2011). Lovastatin had the second highest prescription rates from 24.7% in 2002 to 24.2% in 2006, but it declined after 2007 to 5.8% in 2011. On the other hand, simvastatin became the second commonly used statin since 2007 (21.7%), and its prescription rate peaked in 2009 (27.1%). Rosuvastatin entered the market in 2005, and its prescription rate rapidly increased to 19.5% in 2011. Prescription rates of other statins remained relatively low. Figure 1 shows the prescribing trends of statins over time.

Table 2.

Prescription rates of statins among new statin users

Year 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Yearly cohort size 5956 9056 10 924 10 253 12 178 13 535 15 233 16 499 17 509 17 755
Overall
 Atorvastatin 2014 33.8% 3320 36.7% 3926 35.9% 3610 35.2% 3883 31.9% 4101 30.3% 4322 28.4% 4912 29.8% 5841 33.4% 6357 35.8%
 Fluvastatin 710 11.9% 855 9.4% 1063 9.7% 1159 11.3% 1109 9.1% 1214 9.0% 1284 8.4% 1193 7.2% 1186 6.8% 1063 6.0%
 Lovastatin 1473 24.7% 2829 31.2% 3595 32.9% 3112 30.4% 2951 24.2% 2298 17.0% 1965 12.9% 1724 10.4% 1242 7.1% 1025 5.8%
 Pravastatin 654 11.0% 791 8.7% 813 7.4% 687 6.7% 766 6.3% 776 5.7% 1005 6.6% 1122 6.8% 1438 8.2% 1676 9.4%
 Rosuvastatin NA NA NA 348 3.4% 1690 13.9% 2216 16.4% 2739 18.0% 3082 18.7% 3396 19.4% 3464 19.5%
 Simvastatin 1106 18.6% 1262 13.9% 1529 14.0% 1339 13.1% 1786 14.7% 2940 21.7% 3920 25.7% 4478 27.1% 4412 25.2% 4190 23.6%
Monotherapy 5872 98.6% 8908 98.4% 10 765 98.5% 10 137 98.9% 12 011 98.6% 13 055 96.5% 14 590 95.8% 15 594 94.5% 16 540 94.5% 16 695 94.0%
 Atorvastatin 1984 33.8% 3276 36.8% 3861 35.9% 3572 35.2% 3829 31.9% 4042 31.0% 4266 29.2% 4826 30.9% 5727 34.6% 6224 37.3%
 Fluvastatin 701 11.9% 840 9.4% 1045 9.7% 1145 11.3% 1093 9.1% 1197 9.2% 1268 8.7% 1163 7.5% 1168 7.1% 1034 6.2%
 Lovastatin 1457 24.8% 2777 31.2% 3556 33.0% 3089 30.5% 2915 24.3% 2264 17.3% 1948 13.4% 1691 10.8% 1224 7.4% 1006 6.0%
 Pravastatin 637 10.8% 772 8.7% 799 7.4% 671 6.6% 745 6.2% 758 5.8% 992 6.8% 1108 7.1% 1400 8.5% 1628 9.8%
 Rosuvastatin NA NA NA NA NA NA 343 3.4% 1665 13.9% 2164 16.6% 2680 18.4% 3016 19.3% 3316 20.0% 3386 20.3%
 Simvastatin 1093 18.6% 1243 14.0% 1504 14.0% 1317 13.0% 1764 14.7% 2630 20.1% 3436 23.6% 3790 24.3% 3705 22.4% 3417 20.5%
Combination 84 1.4% 148 1.6% 159 1.5% 116 1.1% 167 1.4% 480 3.5% 643 4.2% 905 5.5% 969 5.5% 1060 6.0%
 Statin + fibrate 70 83.3% 94 63.5% 132 83.0% 95 81.9% 124 74.3% 160 33.3% 161 25.0% 210 23.2% 226 23.3% 249 23.5%
 Statin + ezetimibe 0 0.0% 0 0.0% 0 0.0% 0 0.0% 7 4.2% 280 58.3% 454 70.6% 638 70.5% 652 67.3% 702 66.2%
 Statin + others 14 16.7% 58 39.2% 28 17.6% 22 19.0% 36 21.6% 47 9.8% 30 4.7% 60 6.6% 95 9.8% 114 10.8%
Different intensity of statin therapy
 Low 3039 51.0% 4490 49.6% 5112 46.8% 4518 44.1% 4477 36.8% 4100 30.3% 4065 26.7% 4602 27.9% 4954 28.3% 4852 27.3%
 Moderate 2918 49.0% 4564 50.4% 5785 53.0% 5688 55.5% 7591 62.3% 9261 68.4% 10 903 71.6% 11 634 70.5% 12 200 69.7% 12 599 71.0%
 High 1 0.0% 6 0.1% 32 0.3% 49 0.5% 118 1.0% 187 1.4% 272 1.8% 279 1.7% 365 2.1% 333 1.9%
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Statins were grouped into three levels of intensity according to its ability of lowering LDL-C based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol7 and Rosenson et al 28: (1) high-intensity statins: atorvastatin ≧40 mg/day, rosuvastatin ≧20 mg/day and simvastatin ≧80 mg/day; (2) moderate-intensity statins: 10 mg/day ≦ atorvastatin <40 mg/day, 5 mg/day ≦ rosuvastatin <20 mg/day, 20 mg/day ≦ simvastatin <80 mg/day, pravastatin ≧40 mg/day, lovastatin ≧40 mg/day and fluvastatin ≧80 mg/day; and (3) low-intensity statins: atorvastatin <10 mg/day, rosuvastatin <5 mg/day, simvastatin <20 mg/day, pravastatin <40 mg/day, lovastatin <40 mg/day and fluvastatin <80 mg/day.

Combinations, statin + other lipid-modifying agents.

ACC/AHA, American College of Cardiology/American Heart Association; LDL-C, low-density lipoprotein cholesterol; NA, not applicable.

Figure 1.

Figure 1

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Prescribing rates of statins among new statin users from 2002 to 2011. All values were calculated in patient number. Yearly prescription rate = number of patients prescribed with the specific statin agent / total number of new statin users in the year.

During the study period, almost all patients were prescribed with a single statin when they first started (98.6% in 2002 and 94.0% in 2011). Only 1.4% of patients were prescribed with combination therapy in 2002, with fibrates accounting for 83.3% of the combination therapies. Use of combination therapy increased to 6.0% in 2011, with ezetimibe accounting for 66.2% of combined lipid-lowering drugs.

In 2002, prescription rates of low-intensity and moderate-intensity statins were similar (51.0% and 49.0%). However, prescription rates of moderate-intensity statins gradually increased to 71.0% in 2011, while prescription rates of low-intensity statins gradually decreased to 27.3% in 2011. In comparison, use of high-intensity statins remained low (under 2.1%) during the study period (figure 2).

Figure 2.

Figure 2

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Prescribing rates of statins by intensity. All values were calculated in patient number. Yearly prescription rate = number of patients prescribed with the specific statin agent / total number of new statin users in the year. Statins were grouped into three levels of intensity according to their ability to lower LDL-C based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol7 and Rosenson et al 28: (1) high-intensity statins: atorvastatin ≧40 mg/day, rosuvastatin ≧20 mg/day and simvastatin ≧80 mg/day; (2) moderate-intensity statins: 10 mg/day ≦ atorvastatin <40 mg/day, 5 mg/day ≦ rosuvastatin <20 mg/day, 20 mg/day ≦ simvastatin <80 mg/day, pravastatin ≧ 40 mg/day, lovastatin ≧40 mg/day and fluvastatin ≧80 mg/day; and (3) low-intensity statins: atorvastatin <10 mg/day, rosuvastatin <5 mg/day, simvastatin <20 mg/day, pravastatin <40 mg/day, lovastatin <40 mg/day and fluvastatin <80 mg/day. ACC/AHA, American College of Cardiology/American Heart Association; LDL-C, low-density lipoprotein cholesterol.

Table 3 and figure 3 show the prescription rates of statins among new statin users with/without history of specific diseases. Compared with those without CVD, higher percentages of people with history of coronary events or cerebrovascular events were prescribed atorvastatin (51.4% vs 35.6% and 42.7% vs 35.4%, respectively, in 2011) or rosuvastatin (32.5% vs 19.3% and 27.5% vs 19.1%, respectively, in 2011). In patients with myopathy or liver injury history, prescription rates of different statins did not vary greatly through the study period compared with those without history of the diseases. Similarly, prescription rates of different statins did not vary greatly between people with and without diabetes.

Table 3.

Prescription rates of statins among new statin users with/without disease history

Year 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Yearly number of new statin users 5956 9056 10 924 10 253 12 178 13 535 15 233 16 499 17 509 17 755
With coronary events history NA NA NA NA 201 1.8% 179 1.7% 232 1.9% 219 1.6% 254 1.7% 301 1.8% 309 1.8% 286 1.6%
Atorvastatin NA NA NA NA 104 51.7% 93 52.0% 93 40.1% 94 42.9% 125 49.2% 152 50.5% 159 51.5% 147 51.4%
Fluvastatin NA NA NA NA 32 15.9% 29 16.2% 27 11.6% 24 11.0% 21 8.3% 21 7.0% 14 4.5% 7 2.5%
Lovastatin NA NA NA NA 12 6.0% 10 5.6% 11 4.7% 7 3.2% 4 1.6% 8 2.7% 4 1.3% 4 1.4%
Pravastatin NA NA NA NA 18 9.0% 10 5.6% 21 9.1% 13 5.9% 10 3.9% 15 5.0% 7 2.3% 13 4.6%
Rosuvastatin NA NA NA NA NA NA 6 3.4% 59 25.4% 64 29.2% 76 29.9% 85 28.2% 103 33.3% 93 32.5%
Simvastatin NA NA NA NA 35 17.4% 31 17.3% 21 9.1% 17 7.8% 18 7.1% 20 6.6% 22 7.1% 22 7.7%
Without coronary events history NA NA NA NA 10 723 98.2% 10 074 98.3% 11 946 98.1% 13 316 98.4% 14 979 98.3% 16 198 98.2% 17 200 98.2% 17 469 98.4%
Atorvastatin NA NA NA NA 3822 35.6% 3517 34.9% 3790 31.7% 4007 30.1% 4197 28.0% 4760 29.4% 5682 33.0% 6210 35.6%
Fluvastatin NA NA NA NA 1031 9.6% 1130 11.2% 1082 9.1% 1190 8.9% 1263 8.4% 1172 7.2% 1172 6.8% 1056 6.0%
Lovastatin NA NA NA NA 3583 33.4% 3102 30.8% 2940 24.6% 2291 17.2% 1961 13.1% 1716 10.6% 1238 7.2% 1021 5.8%
Pravastatin NA NA NA NA 795 7.4% 677 6.7% 745 6.2% 763 5.7% 995 6.6% 1107 6.8% 1431 8.3% 1663 9.5%
Rosuvastatin NA NA NA NA NA NA 342 3.4% 1631 13.7% 2153 16.2% 2663 17.8% 2997 18.5% 3293 19.2% 3371 19.3%
Simvastatin NA NA NA NA 1494 13.9% 1308 13.0% 1765 14.8% 2924 22.0% 3902 26.1% 4458 27.5% 4390 25.5% 4168 23.9%
With cerebrovascular events history NA NA NA NA NA NA NA NA 661 5.4% 735 5.4% 820 5.4% 821 5.0% 893 5.1% 878 5.0%
Atorvastatin NA NA NA NA NA NA NA NA 315 47.7% 325 44.2% 328 40.0% 321 39.1% 389 43.6% 375 42.7%
Fluvastatin NA NA NA NA NA NA NA NA 68 10.3% 71 9.7% 77 9.4% 68 8.3% 78 8.7% 63 7.2%
Lovastatin NA NA NA NA NA NA NA NA 62 9.4% 52 7.1% 61 7.4% 48 5.9% 43 4.8% 26 3.0%
Pravastatin NA NA NA NA NA NA NA NA 48 7.3% 41 5.6% 53 6.5% 39 4.8% 40 4.5% 59 6.7%
Rosuvastatin NA NA NA NA NA NA NA NA 99 15.0% 149 20.3% 173 21.1% 201 24.5% 223 25.0% 241 27.5%
Simvastatin NA NA NA NA NA NA NA NA 69 10.4% 97 13.2% 128 15.6% 146 17.8% 120 13.4% 115 13.1%
Without cerebrovascular events history NA NA NA NA NA NA NA NA 11 517 94.6% 12 800 94.6% 14 413 94.6% 15 678 95.0% 16 616 94.9% 16 877 95.1%
Atorvastatin NA NA NA NA NA NA NA NA 3568 31.0% 3776 29.5% 3994 27.7% 4591 29.3% 5452 32.8% 5982 35.4%
Fluvastatin NA NA NA NA NA NA NA NA 1041 9.0% 1143 8.9% 1207 8.4% 1125 7.2% 1108 6.7% 1000 5.9%
Lovastatin NA NA NA NA NA NA NA NA 2889 25.1% 2246 17.6% 1904 13.2% 1676 10.7% 1199 7.2% 999 5.9%
Pravastatin NA NA NA NA NA NA NA NA 718 6.2% 735 5.7% 952 6.6% 1083 6.9% 1398 8.4% 1617 9.6%
Rosuvastatin NA NA NA NA NA NA NA NA 1591 13.8% 2067 16.2% 2566 17.8% 2881 18.4% 3173 19.1% 3223 19.1%
Simvastatin NA NA NA NA NA NA NA NA 1717 14.9% 2843 22.2% 3792 26.3% 4332 27.6% 4292 25.8% 4075 24.2%
With diabetes history 1947 32.7% 2884 31.8% 3212 29.4% 3272 31.9% 3888 31.9% 4362 32.2% 4785 31.4% 5366 32.5% 5737 32.8% 5540 31.2%
Atorvastatin 705 36.2% 1177 40.8% 1287 40.1% 1207 36.9% 1256 32.3% 1360 31.2% 1302 27.2% 1602 29.9% 1870 32.6% 1987 35.9%
Fluvastatin 227 11.7% 273 9.5% 293 9.1% 398 12.2% 392 10.1% 366 8.4% 445 9.3% 422 7.9% 437 7.6% 343 6.2%
Lovastatin 428 22.0% 747 25.9% 919 28.6% 857 26.2% 842 21.7% 702 16.1% 572 12.0% 541 10.1% 389 6.8% 325 5.9%
Pravastatin 237 12.2% 287 10.0% 232 7.2% 233 7.1% 276 7.1% 259 5.9% 332 6.9% 365 6.8% 496 8.7% 531 9.6%
Rosuvastatin NA NA NA NA NA NA 140 4.3% 595 15.3% 754 17.3% 941 19.7% 1024 19.1% 1126 19.6% 1042 18.8%
Simvastatin 350 18.0% 400 13.9% 481 15.0% 437 13.4% 528 13.6% 923 21.2% 1194 25.0% 1414 26.4% 1421 24.8% 1317 23.8%
Without diabetes history 4009 67.3% 6172 68.2% 7712 70.6% 6981 68.1% 8290 68.1% 9173 67.8% 10 448 68.6% 11 133 67.5% 11 772 67.2% 12 215 68.8%
Atorvastatin 1309 32.7% 2143 34.7% 2639 34.2% 2403 34.4% 2627 31.7% 2741 29.9% 3020 28.9% 3310 29.7% 3971 33.7% 4370 35.8%
Fluvastatin 483 12.1% 582 9.4% 770 10.0% 761 10.9% 717 8.7% 848 9.2% 839 8.0% 771 6.9% 749 6.4% 720 5.9%
Lovastatin 1045 26.1% 2082 33.7% 2676 34.7% 2255 32.3% 2109 25.4% 1596 17.4% 1393 13.3% 1183 10.6% 853 7.3% 700 5.7%
Pravastatin 417 10.4% 504 8.2% 581 7.5% 454 6.5% 490 5.9% 517 5.6% 673 6.4% 757 6.8% 942 8.0% 1145 9.4%
Rosuvastatin NA NA NA NA NA NA 208 3.0% 1095 13.2% 1462 15.9% 1798 17.2% 2058 18.5% 2270 19.3% 2422 19.8%
Simvastatin 756 18.9% 862 14.0% 1048 13.6% 902 12.9% 1258 15.2% 2018 22.0% 2726 26.1% 3064 27.5% 2991 25.4% 2873 23.5%
With myopathy history NA NA NA NA 2924 26.8% 2806 27.4% 3342 27.4% 3816 28.2% 4202 27.6% 4502 27.3% 4068 23.2% 5061 28.5%
Atorvastatin NA NA NA NA 1036 35.4% 949 33.8% 1016 30.4% 1135 29.7% 1102 26.2% 1308 29.1% 1616 39.7% 1769 35.0%
Fluvastatin NA NA NA NA 289 9.9% 314 11.2% 299 9.0% 332 8.7% 355 8.5% 319 7.1% 335 8.2% 279 5.5%
Lovastatin NA NA NA NA 979 33.5% 895 31.9% 880 26.3% 671 17.6% 581 13.8% 486 10.8% 364 9.0% 291 5.8%
Pravastatin NA NA NA NA 214 7.3% 190 6.8% 200 6.0% 199 5.2% 281 6.7% 302 6.7% 448 11.0% 470 9.3%
Rosuvastatin NA NA NA NA NA NA 110 3.9% 479 14.3% 595 15.6% 713 17.0% 814 18.1% 923 22.7% 924 18.3%
Simvastatin NA NA NA NA 407 13.9% 348 12.4% 472 14.1% 888 23.3% 1170 27.8% 1277 28.4% 1283 31.5% 1331 26.3%
Without myopathy history NA NA NA NA 8000 73.2% 7447 72.6% 8836 72.6% 9719 71.8% 11 031 72.4% 11 997 72.7% 12 541 71.6% 12 694 71.5%
Atorvastatin NA NA NA NA 2890 36.1% 2661 35.7% 2867 32.5% 2966 30.5% 3220 29.2% 3604 30.0% 4225 33.7% 4588 36.1%
Fluvastatin NA NA NA NA 774 9.7% 845 11.4% 810 9.2% 882 9.1% 929 8.4% 874 7.3% 851 6.8% 784 6.2%
Lovastatin NA NA NA NA 2616 32.7% 2217 29.8% 2071 23.4% 1627 16.7% 1384 12.6% 1238 10.3% 878 7.0% 734 5.8%
Pravastatin NA NA NA NA 599 7.5% 497 6.7% 566 6.4% 577 5.9% 724 6.6% 820 6.8% 990 7.9% 1206 9.5%
Rosuvastatin NA NA NA NA NA NA 238 3.2% 1211 13.7% 1622 16.7% 2026 18.4% 2268 18.9% 2473 19.7% 2540 20.0%
Simvastatin NA NA NA NA 1122 14.0% 991 13.3% 1314 14.9% 2053 21.1% 2750 24.9% 3201 26.7% 3129 25.0% 2859 22.5%
With liver injury history NA NA NA NA 856 7.8% 798 7.8% 907 7.4% 1040 7.7% 1075 7.1% 1187 7.2% 1375 7.9% 1403 7.9%
Atorvastatin NA NA NA NA 369 43.1% 304 38.1% 294 32.4% 301 28.9% 324 30.1% 367 30.9% 429 31.2% 519 37.0%
Fluvastatin NA NA NA NA 69 8.1% 86 10.8% 90 9.9% 91 8.8% 79 7.4% 79 6.7% 94 6.8% 84 6.0%
Lovastatin NA NA NA NA 255 29.8% 219 27.4% 211 23.3% 183 17.6% 123 11.4% 88 7.4% 79 5.8% 75 5.4%
Pravastatin NA NA NA NA 51 6.0% 45 5.6% 65 7.2% 65 6.3% 68 6.3% 86 7.3% 134 9.8% 147 10.5%
Rosuvastatin NA NA NA NA NA NA 31 3.9% 121 13.3% 169 16.3% 198 18.4% 221 18.6% 258 18.8% 246 17.5%
Simvastatin NA NA NA NA 112 13.1% 113 14.2% 127 14.0% 232 22.3% 284 26.4% 346 29.2% 381 27.7% 332 23.7%
Without liver injury history NA NA NA NA 10 068 92.2% 9455 92.2% 11 271 92.6% 12 495 92.3% 14 158 92.9% 15 312 92.8% 16 134 92.1% 16 352 92.1%
Atorvastatin NA NA NA NA 3557 35.3% 3306 35.0% 3589 31.8% 3800 30.4% 3998 28.2% 4545 29.7% 5412 33.5% 5838 35.7%
Fluvastatin NA NA NA NA 994 9.9% 1073 11.4% 1019 9.0% 1123 9.0% 1205 8.5% 1114 7.3% 1092 6.8% 979 6.0%
Lovastatin NA NA NA NA 3340 33.2% 2893 30.6% 2740 24.3% 2115 16.9% 1842 13.0% 1636 10.7% 1163 7.2% 950 5.8%
Pravastatin NA NA NA NA 762 7.6% 642 6.8% 701 6.2% 711 5.7% 937 6.6% 1036 6.8% 1304 8.1% 1529 9.4%
Rosuvastatin NA NA NA NA NA NA 317 3.4% 1569 13.9% 2048 16.4% 2541 18.0% 2861 18.7% 3138 19.5% 3218 19.7%
Simvastatin NA NA NA NA 1417 14.1% 1226 13.0% 1659 14.7% 2709 21.7% 3636 25.7% 4132 27.0% 4031 25.0% 3858 23.6%
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Individuals were defined as having a history of the following diseases if they have a diagnosis within certain years prior to the given year: coronary event (3 years), cerebrovascular event (5 years), diabetes (1 year), myopathy (3 years) and liver injury (3 years).

NA, not available.

Figure 3.

Figure 3

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Prescribing rates of statins among new statin users with/without history of specific diseases.

Table 4 indicates the findings of the associations between certain disease history and prescription of high- or moderate-intensity statins. Patients with CVD history were more likely to be prescribed moderate-intensity or high-intensity statins (OR ranged from 1.52 to 2.83 during the study period, p<0.05). Similar results were found in patients with cerebrovascular events history compared with those without (OR ranged from 1.17 to 1.88 during 2006–2011, p<0.05). However, patients with diabetes history were less likely to be prescribed moderate-intensity or high-intensity statins compared with patients without diabetes history (OR ranged from 0.83 to 0.90 during 2007–2011, p<0.05). No substantial differences in prescribing patterns of statins were observed throughout the study period in groups with versus without history of myopathy or liver injury (table 4).

Table 4.

Associations between disease history and prescription of moderate-intensity or high-intensity statins

Year 2004 2005 2006 2007 2008 2009 2010 2011
OR† (95% CI)
History of coronary events 2.04* 2.55* 2.83* 1.69* 2.39* 1.80* 2.06* 1.52*
(1.51 to  2.76) (1.80 to 3.59) (2.01 to 3.99) (1.22 to 2.35) (1.66 to 3.44) (1.34 to 2.42) (1.52 to 2.80) (1.13 to 2.03)
History of cerebrovascular events – – 1.88* 1.61* 1.17* 1.40* 1.66* 1.61*
– – (1.56 to 2.25) (1.34 to 1.93) (0.99 to 1.38) (1.18 to 1.65) (1.40 to 1.96) (1.36 to 1.91)
History of diabetes 1.17* 1.08* 1.01 0.88* 0.90* 0.83* 0.85* 0.83*
(1.08 to 1.27) (0.99 to 1.18) (0.93 to 1.09) (0.81 to 0.95) (0.83 to 0.97) (0.77 to 0.89) (0.79 to 0.91) (0.77 to 0.89)
History of myopathy 0.97 0.95 0.93 0.99 0.97 1.00 0.94 0.96
(0.89 to 1.05) (0.87 to 1.04) (0.86 to 1.01) (0.91 to 1.07) (0.90 to 1.05) (0.73 to 1.08) (0.87 to 1.01) (0.89 to 1.03)
History of liver injury 1.29* 1.19 0.96 1.04 1.10 1.15* 0.95 1.04
(1.12 to 1.49) (1.02 to 1.37) (0.84 to 1.11) (0.91 to 1.20) (0.95 to 1.27) (1.00 to 1.31) (0.84 to 1.07) (0.92 to 1.17
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*Indicates significant difference in prescription rate between patient with certain medical history and those without; p value <0.05.

†OR was calculated as the odds of being prescribed high-intensity or moderate-intensity statins for those with certain disease history compared with those without.

Statins were grouped into three levels of intensity according to its ability of lowering LDL-C based on 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol7 and Rosenson et al 28: (1) high-intensity statins: atorvastatin 40 mg/day, rosuvastatin  20 mg/day and simvastatin 80 mg/day; (2) moderate-intensity statins: 10  mg/day atorvastatin < 40?mg/day, 5 mg/day rosuvastatin < 20 mg/day, 20 mg/day simvastatin < 80 mg/day, pravastatin 40 mg/day, lovastatin 40 mg/day and fluvastatin 80 mg/day; and (3) low-intensity statins: atorvastatin <10 mg/day, rosuvastatin <5 mg/day, simvastatin <20 mg/day, pravastatin <40 mg/day, lovastatin <40 mg/day and fluvastatin <80 mg/ day. Individuals were defined as having a history of the following diseases if they have a diagnosis within certain years prior to the given year: coronary event (3 years), cerebrovascular event (5 years), diabetes (1 year), myopathy (3 years) and liver injury (3 years).

ACC/AHA, American College of Cardiology/American Heart Association; LDL-C, low-density lipoprotein cholesterol.

Discussion

This longitudinal study of a national cohort found that more than half statin users were initiated on a single statin, with atorvastatin being the most commonly prescribed statin over the last decade in Taiwan. Use of moderate-intensity statins increased by 22.0% between 2002 and 2011, while use of high-intensity statins remained low. Lastly, patients with history of coronary events or cerebrovascular events were more likely to be prescribed higher intensity statins compared with those without. Prescribing of higher intensity statins was not greater among people with diabetes compared with those without during 2007–2011. This difference was also not seen in people with versus without history of myopathy or liver injury.

From 2002 to 2011, initiation of statins increased over time, similar to studies from other countries.18 39–41 Initiation of statins in Taiwan has grown from 0.6% in 2002 to 1.8% in 2011. Our findings are similar to studies from other countries that found similar utilisation rates and increasing trend over time. For instance, a study used data of Italian local pharmacies and demonstrated incidence of statin exposure growing from 0.36% in 1994 to 0.74% in 2003.42 Another study, which was also conducted in Italy, exhibited yearly incidence of statin use increasing from 13.3/1000 inhabitants in 2005 to 19.5/1000 inhabitants in 2010 among people aged 15 and over.39 A study by Svensson et al aligned with the previous results showing annual rates of new statin use ranging from 14 to 20/1000 person-years.40

Our study found that atorvastatin had the highest prescription rate in Taiwan throughout the entire study. It was first introduced into Taiwan’s market in 2000 and its market share surged to surpass other agents of the same drug class since the first study year.21 In other countries, atorvastatin has also been one of the most commonly used statins.39 40 43 The popularity of atorvastatin might be attributed to favourable research results suggesting its clinical benefits in preventing major coronary events44 as well as marketing strategies of the pharmaceutical company.45 When examining trends of different statins, it was noted that trends of atorvastatin and simvastatin exhibited opposite directions (figure 1). Since both statins were moderate-to-high potency agents, their similar potency may be a reason for the substitution observed.12 46 Another high-potency statin―rosuvastatin―manifested an increase in prescription rates since its market entry at 2005. The growth in use of atorvastatin, simvastatin (+/- ezetimibe) and rosuvastatin suggests treatment trending towards use of high-potency or moderate-to-high-intensity statin therapy, which is aligned with major clinical guidelines.7–9

The majority of statin regimen stayed within the moderate-intensity range rather than high-intensity therapy, which remained less than 5% during the study period. In a study from USA, relatively lower percentage (approximately 20% of total statin use) of high-intensity statin therapy was reported among adults ≧40 years old during 2002–2013.47 In comparison, our study reveals substantially low use of high-intensity statin, suggesting that there is room for improving rational use of statins in Taiwan.

Few statin users initiated with combination therapy overall. Use of combined lipid-lowering agents shifted from fibrates (83.3% in 2002) to ezetimibe (66.2% in 2011). Ezetimibe entered Taiwan’s market under the National Insurance coverage in 2006 as a combination drug with simvastatin (tradename Vytorin). High uptake of ezetimibe products might be associated with the evidence that ezetimibe plus simvastatin is more effective in lowering LDL-C than simvastatin alone.48 49

Our findings demonstrated an association between having a history of CVD and high-intensity or moderate-intensity statin use. Similarly other studies have reported that patients with CVD histories were prescribed statins with higher intensity or doses.19 50 Use of statins among these individuals might have been appropriately influenced by clinical guidelines and related evidence suggesting more intensive statin therapy reduces cardiovascular events in patients with prior CVD.22 While diabetes has been viewed as a coronary risk equivalent,51 we did not find greater use of higher intensity statins among those with diabetes. A possible explanation might include the accumulating evidence suggesting the association between statin use and increasing risk of diabetes52 53 and the deterioration of glucose control in patients receiving higher intensity statin regimens.54 Appropriateness of statin use among diabetes needs further investigation. Interestingly, we did not find different patterns of statin use between those with and without history of myopathy or liver diseases. This finding suggests that these side effects might not be of a primary concern when prescribing statin therapy in Taiwan.

This study contributes to the literature by examining the prescribing patterns of statins during 2002–2011 in Taiwan, including statin choices among patients with certain medical histories. Despite these strengths, it does have limitations. First, our analysis was based on claims data, which do not contain patients’ biochemical test data (such as level of LDL-C), so we could not assess prescription patterns by disease severity. Second, this study only examined statin use among new users; we did not assess switches between statins. Further research is needed to address these gaps. As new PCSK9 inhibitors become available on Taiwan’s NHI, our findings provide baseline trends that can be used in a future study to examine how new PCSK9 inhibitors impact the market of cholesterol medications.

Conclusion

Our study with national cohorts of new statin users in each year during 2002–2011 in Taiwan found that the majority of new users initiated on statin monotherapy, and atorvastatin was the most commonly prescribed statin. While patients with history of CVD were more likely to be prescribed higher intensity statins compared with those without, which is consistent with clinical guidelines, such difference was not found comparing those with and without diabetes. Appropriateness of statin use among diabetes needs further investigation.

Supplementary file

bmjopen-2016-014150supp001.doc (88KB, doc)

Supplementary Material

Reviewer comments
bmjopen-2016-014150.reviewer_comments.pdf (307.3KB, pdf)
Author's manuscript
bmjopen-2016-014150.draft_revisions.pdf (2.2MB, pdf)

Footnotes

Contributor: JCH and HCH conceptualised and designed the study. HCH collected data, performed analysis and drafted the manuscript. JCH and CYL reviewed all data and revised the manuscript critically for intellectual content. All authors approved the final version for submission.

Competing interests: None declared.

Ethics approval: National Cheng Kung University Hospital.

Provenance and peer review: Not commissioned; externally peer reviewed.

Data sharing statement: The authors have obtained nationwide, monthly claims data for lipid-lowering agents, from 2002 to 2011, from the Taiwan National Health Insurance Research Database (NHIRD). NHIRD does not permit external sharing of any of the data elements. No additional data available.

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