European Review for Medical and Pharmacological Sciences 2013; 17: 410-419 Pattern analysis and variations in the utilization of antihypertensive drugs in Taiwan: a six-year study L.-Y. HUANG1,2, W.-Y. SHAU1, H.-C. CHEN3, S. SU2, M.-C. YANG2, H.-L. YEH4,5, M.-S. LAI3,6 1Division of Health Technology Assessment, Center for Drug Evaluation, Taipei, Taiwan 2Graduate Institute of Health Care Organization Administration, College of Public Health, National Taiwan University, Taipei, Taiwan 3Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan 4Department of Cardiology, Sijhih Cathay General Hospital, Taipei, Taiwan 5School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan 6Center for Comparative Effectiveness Research, National Clinical Trial and Research Center, National Taiwan University Hospital, Taipei, Taiwan Abstract. – BACKGROUND: In the last few CONCLUSIONS: The consumption of antihy- years there have been changed in the pattern of pertension drugs in Taiwan increased during the consumption of antihypertensive drugs in other period studied and the highest average annual countries. Factors causing this variability in- increases were for ARBs and CCBs. Overall con- clude differences in the effectiveness of detec- sumption of antihypertension drugs also in- tion, guidelines for the management of hyperten- creased in other countries, but differences in the sion, and differences in national health insur- relative increase for each class of drug suggest ance systems among countries. that further study may be required to clarify the AIM: The aim of this study was to reveal pat- origins and causes. terns in the use of antihypertensive drugs in Tai- wan over a six year period (2001 to 2006) and com- Key Words: pare these results with data from other countries. Antihypertensive drugs, Total defined daily dose, MATERIALS AND METHODS: This study per- Angiotensin-II receptor blockers, Calcium channel formed descriptive analysis of data from the Nation- blockers, Angiotensin-converting enzyme inhibitors. al Health Insurance Research Database (NHIRD) of Taiwan, and compared these findings with similar findings from around the world. Quantities were standardized using the defined daily dose (DDD) per 1000 inhabitants per day (DID) in accordance with WHO anatomical therapeutic classification and Introduction DDD measurement methodology. RESULTS: The total number of DDDs pre- Considerable variability in the prevalence of scribed in Taiwan increased from 0.66 billion in hypertension (5.3 to 42.3% of different popula- 2001 to 1.08 billion in 2006, representing 80.6 tions) has been observed in previous studies1. and 129.2 DID in 2001 and 2006, respectively. This variability may be due to differences in the This indicates a significant increase in the pre- 2,3 scription of antihypertensive drugs in Taiwan measurement of blood pressure , age ranges, over this period. The average annual increase and the definitions used for hypertension4. In the ranged from 10.7% for calcium channel blockers last few years there have been changed in the (CCBs) to 22.1% for angiotensin II receptor pattern of consumption of antihypertensive blockers (ARBs). All of these patterns were sta- drugs in other countries1. The factors causing tistically significant (p < 0.05). The rapid increase this variability include differences in the effec- in the use of ARBs resulted in its surpassing 1 ACEIs with the second highest DID (21.9) in tiveness of detection , different guidelines for 1 2006. Though the proportional use of CCBs and the management of hypertension , differences in ARBs has increased significantly, the use of thi- the national health insurance systems of various azide diuretics remains low. countries1, differences in the measurement of 410 Corresponding Author: Mei-Shu Lai, MD; e-mail: [email protected] Pattern analysis and variations in the utilization of antihypertensive drugs in Taiwan: a six-year study blood pressure2,3, different definitions of hyper- 3. Beta blocking agents (BBs): C07A A. Non-se- tension4 and different age ranges1. Few studies lective beta blocking agents, plain; C07A B. have specifically investigated patterns in the use Selective beta blocking agents, plain; C07A G. of antihypertensive drugs in Taiwan. Chou et al. Alpha and beta blocking agents; C07B, C07C presented the patterns of antihypertensive med- and C07D. Beta blocking agents and diuretics; ications in Taiwan according to their pharmaco- C07F. Beta blocking agents and other antihy- logical classifications5. Their results indicated pertensives8,9; that calcium antagonists were the most frequent- 4. Calcium channel blockers: C08: C08C and ly prescribed antihypertensive medication, ap- C08D. Calcium channel blockers8,9; pearing in 54.9% of all hypertension related pre- 5. ACE inhibitors (ACEIs): C09A. ACE in- scriptions in 19985. The second was beta-block- hibitors, plain; C09B A. ACE inhibitors and ers (43.5%), followed by angiotensin-converting diuretics; C09B B. ACE inhibitors and calcium enzyme inhibitors (ACEIs) (31.5%), and diuret- channel blockers8,9; ics (23.2%)5. The aim of this study was to de- 6. Angiotensin II antagonists (ARBs): C09C. An- scribe the utilization patterns of antihypertensive giotensin II antagonists, plain; C09D. An- drugs in Taiwan over a six-year period (2001- giotensin II antagonists, combinations8,9. 2006) and compare the results with data from 7. Other antihypertensives: C02CA. Alpha- other countries. adrenoreceptor antagonists; C02A. Antiadrener- gic agents, centrally acting; C02D. Arteriolar smooth muscle, agents acting on; C02L. Antihy- Materials and Methods pertensives and diuretics in combination8,9. Data Collection Method of Analysis This study employed descriptive analysis of all Medications were quantified in defined daily prescriptions for antihypertensive drugs between doses by assigning defined daily dose (DDD) 2001 and 2006, from the National Health Insur- units to each NHIRD item using the Anatomical ance Research Database (NHIRD) of Taiwan. Therapeutic Chemical (ATC) classification sys- The NHI is the Taiwanese universal health insur- tem8. All NHIRD items are classified by the ATC ance program implemented in March 1995. By classification system, and can be directly linked 2006, the NHI covered approximately 98% of the to DDD units using the ATC Index9. Taiwanese population, and 97% of hospitals and First, the total number of DDDs dispensed in clinics throughout the nation6,7. Antihypertensive each record of the NHIRD set is calculated to de- drugs were evaluated according to the Anatomi- termine the dose strength for each item using the cal Therapeutical Chemical Classification/De- following formula9,10: fined Daily Doses (ATC/DDD) system developed N*M*Q by the World Health Organization8,9. This study DDDs = ––––––––––– categorized the antihypertensive drugs into seven DDD unit major classes (ATC codes are listed in parenthe- ses): renin-angiotensin system (ACEIs, C09A, where N is the number of prescriptions dis- C09B), angiotensin-II receptor blockers (ARBs, pensed per record, M is the strength of each dose C09C, C09D); beta-blockers (C07); calcium (milligrams), Q is the average quantity of doses channel blockers (CCB) (C08); thiazide-type di- per prescription and DDD unit is one defined uretics (C03A); other diuretics (C03B, C03C, daily dose for the particular NHIRD item9. When C03D, C03E); and others (C02)8,9. All anti-hy- used for comparison, the number of DDDs pre- pertensive drugs considered in this study be- scribed is generally given per 1000 inhabitants longed to subgroups of the seven major therapeu- per day9,10. This method of standardization ad- tic groups, classified as follows8,9: justs for the size of the population under study, enabling meaningful comparisons of drug use 1. Thiazide type Diuretics: C03A across years and among different countries9,12. 2. Other Diuretics: C03B. Low-ceiling diuretics, Population related data was obtained from Na- plain; C03C. High-ceiling diuretics, plain; tional Statistics in Taiwan11. This study presents C03D. Potassium-sparing agents, plain; C03E. the DDDs per 1000 inhabitants per day (DID)9,12 Diuretics and potassium-sparing agents in com- of each ATC category by the year and throughout bination. the entire period of study. 411 L.-Y. Huang, W.-Y. Shau, H.-C. Chen, S. Su, M.-C. Yang, H.-L. Yeh, M.-S. Lai Data Sources software SAS for Windows (version 9.1; SAS In- The data in this study was derived from the en- stitute, Cary, NC, USA) was used to conduct all tire population of Taiwan, because everyone is data analysis. insured according to the law. Since March 1, 1995, when Taiwan implemented universal na- tional health insurance (NHI) legislation, cover- Results age has increased from 57% to 98% of the popu- lation6,13. As of 2007, 22.60 million of Taiwan’s For the drugs included in the present study, the 22.96 million citizens were enrolled in this pro- total number of DDDs prescribed in Taiwan in- gram8. This data (which includes outpatient and creased from 0.66 billion in 2001 to 1.08 billion in inpatient records) provides national estimates of 2006, representing 80.1 and 129.2 DID in 2001 exposure to antihypertensive drugs, enables the and 2006, respectively. This indicates a significant monitoring of changes in usage and allows com- increase in the prescription of antihypertensive parison of data from Taiwan with those from oth- drugs in Taiwan over this period. Figure 1 presents er countries. the DID and annual trends according to ATC groupings of antihypertensive drugs used from Statistical Analysis 2001 to 2006. All seven classes of drugs showed To analyse annual trends in the use of these an increase in use with average yearly increases drugs, this study employed linear regression to from 4.5% for ACE inhibitors to 22.1% for ARB calculate the mean change of DID per year, using (Figure 1). All of the trends are statistically signifi- DID as a dependent variable and regressed yearly cant (p < 0.05) (Figure 1). Among the classes of figures as continuous variables.