Prev a Lence of Antilipemic Drug Use in Tai Wan: Anal Y Sis of a Sam

Orig i nal Article

J Chin Med Assoc Preva lence of Antilipemic Drug Use in 2003;66:39-45 Taiwan: Analy sis of a Sam pling Co hort within the National Health In sur ance

Tzeng-Ji Chen1,3 Back ground. Hyperlipidemia is a ma jor risk fac tor of car dio vas cu lar dis eases. We Shing-Jong Lin2,4 in ves ti gated the uti li za tion of antilipemic drugs at the out pa tient sec tor within the Na- Liang-Kung Chen1,3 tional Health In sur ance in Tai wan. 1,3 Shinn-Jang Hwang Methods. We ob tained the first co hort (n = 50,000) dataset from the Na tional Health 5 Li-Fang Chou In sur ance Re search Da ta base and an a lyzed the out pa tient claim files of the co hort in 1 De part ment of Fam ily Med i cine; 2000. The antilipemic drugs were de fined as the drug items be long ing to the group 2 Di vi sion of Car di ol ogy, De part ment of C10 (se rum lipid re duc ing agents) of the An a tom i cal Ther a peu tic Chem i cal clas si fi- Med i cine, Tai pei Vet erans Gen eral ca tion sys tem. Hos pi tal; and 3 Di vi sion of Fam ily Med i cine; Results. Among the co hort with 46,614 el i gi ble peo ple, 760 pa tients had ever re- 4 In sti tute of Clin i cal Med i cine, Na tional ceived antilipemic drugs (prev a lence: 1.6%). The group 60 - 69 years of age had the Yang-Ming Uni ver sity School of great est age-specific prev a lence (7.2%), fol lowed by the group over 70 years of age Med i cine; and (6.0%). There were more male than fe male pa tients, but fe male pa tients out num bered 5 De part ment of Pub lic Fi nance, Na tional male pa tients be fore the age of 49 years. The antilipemic drugs had been pre scribed Chengchi Uni ver sity, Tai pei, Tai wan, 3,850 times to tally with 70,272 de fined daily doses (DDDs). On an av er age, a pa tient R.O.C. with antilipemic ther apy re ceived 5.1 (± 4.5) pre scrip tions of antilipemic drugs in one year and a pre scrip tion con tained 18.3 (± 11.5) DDDs. We mea sured 4.1 DDDs per 1,000 in hab it ants per day for all antilipemic drug use in 2000. The statins and Key Words fibrates pre dom i nated the antilipemic drug use. While gemfibrozil was most pop u lar antilipemic agents; in re spect of re cip i ents and pre scrip tion items, simvastatin had the larg est amount of drug uti li za tion; use in unit of DDDs. Di a be tes mellitus co-existed in 37.8% of the pa tients with na tional health pro grams; antilipemic ther apy and the stan dard ized mor bid ity ra tio (SMR) was 3.34. The other pharmacoepidemiology; con com i tant dis eases in cluded es sen tial hy per ten sion (rate: 48.8%, SMR: 2.40) and preva lence other heart dis ease (rate: 30.7%, SMR: 2.36). Conclu sions. Statins were the lead ing antilipemic drugs in Tai wan. The us ers of antilipemic drugs were more likely to have con com i tant di a be tes mellitus, hy per ten- sion and heart dis ease.

l though hyperlipidemia has been rec og nized as a Since 1995, a Na tional Health In sur ance (NHI) pro gram Ama jor risk fac tor of car dio vas cu lar dis eases for de- cov er ing nearly all pop u la tion has been im ple mented in cades, the ben e fit of lipid low er ing was dem on strated Tai wan. With the avail abil ity of lon gi tu di nal med i ca tion late in 1994 by a large, ran dom ized clin i cal trial.1 De spite data of in di vid ual pa tients within the NHI, we had the op- the clin i cal and eco nomic sig nif i cance as so ci ated with por tu nity of study ing not only the na tional con sump tion the antilipemic drugs, lit tle was known about their uti li- of antilipemic drugs, but also the prev a lence of anti- za tion at the na tional level.2,3 Among the mem ber coun- lipemic drug use in this coun try. tries of the OECD (Or gani sa tion for Economic Co - In this current study, we surveyed the out pa tient operation and De vel op ment), only seven coun tries had dataset of the NHI claims from a 50,000-person co hort in data based on na tional phar ma ceu ti cal sales in 1998.4 the cal en dar year 2000. Be side cal cu lat ing the age- and

Re ceived: June 22, 2002. Cor re spon dence to: Shing-Jong Lin, MD, Di vi sion of Car di ol ogy, Tai pei Vet erans Gen eral Hos pi tal, Ac cepted: October 22, 2002. 201, Sec. 2, Shih-Pai Road, Tai pei 112, Tai wan. Fax: +886-2-2874-8374; E-mail: [email protected]

39 Tzeng-Ji Chen et al. Jour nal of the Chi nese Med i cal As so ci a tion Vol. 66, No. 1 sex-specific prev a lence of antilipemic drug use and the antilipemic drugs have been reg is tered in the NHI drug con sump tion of sin gle antilipemic drugs in Tai wan, we file since 1995. inves ti gated the health condi tions of the patients with We first iden ti fied the or der re cords with pre scrip- antilipemic ther apy by eval u at ing their con com i tant dis- tions of antilipemic drugs in the R01_OO2000.DAT eases. and then found their asso ci ated visit re cords in the R01_CD2000.DAT. These records were extracted for fur ther anal y ses. Be cause the bile acid sequestrants, es- METHODS pe cially cholestyramine, were not solely used in treat ing hyperlipidemia, we ex cluded their re cords with out a re- Data sources lated di ag no sis, i.e. 272 as the first three dig its of di ag- We obtained the first cohort dataset from the Na - nos tic codes in ICD-9-CM (In ter na tional Clas si fi ca tion tional Health In sur ance Re search Da ta base (NHIRD; of Dis eases, 9th Re vi sion, Clini cal Modi fi ca tion). In a http://www.nhri.org.tw/nhird/). The cohort included visit re cord, up to three di ag no ses were coded ac cord ing 50,000 peo ple ran domly sam pled from 23,753,407 peo- to the ICD-9-CM. ple who had ever been in sured un der the NHI since 1995. The use of antilipemic drugs among the co hort was The dataset in cluded all in sur ance claims of these 50,000 strati fied by the recip i ents’ age/sex to deter mine the people from 1996 to 2000. The purpose of the NHIRD preva lence. We also strat i fied the pre scrip tions of anti- and the structure of the NHI claim files had been de - lipemic drugs by their chemi cal substances (ATC 5th scribed in de tails in our pre vi ous study.5 level) and cal cu lated the num ber of re cip i ents, the num- In the current study, we an a lyzed only the out pa- ber of pre scribed items, and the to tal pre scribed amount tient visit and or der files of the co hort dataset in 2000 in unit of DDDs in each main in gre di ent. Be sides, the (R01_CD2000.DAT, and R01_OO2000.DAT). These numbers of DDDs per 1,000 in hab it ants per day were files con tained the claims of out pa tient (in clud ing emer- cal cu lated to re flect the pro por tion of the Tai wan ese pop- gency) visits to clinics of West ern medi cine, den tistry u la tion treated daily with each kind of antilipemic drugs and tra di tional Chi nese med i cine. Be sides, we ob tained a at the out pa tient sec tor. com plete file of 21,146 ap proved drug items of West ern Hyperlipidemia usu ally co-existed with other dis - med i cine in Tai wan from the web site of the Bu reau of eases. To calcu late the frequency of con com i tant dis - Na tional Health In sur ance (BNHI; http://www.nhi.gov.tw/; eases in the pa tients re ceiv ing antilipemic drugs, we ex- ac cessed May 25th, 2001). The BNHI also of fered a list tracted the identi fi ca tion num bers of these pa tients and of ATC (the An a tom i cal Ther a peu tic Chem i cal clas si fi- found out all of their visit re cords and di ag no ses, not lim- ca tion sys tem) codes (4th level) for each drug item.6 We ited to the re cords with prescrip tions of antilipemic added the 5th level cod ing for the rel e vant drug items and drugs. Be cause more than 12,000 codes in the ICD- found their De fined Daily Dose (DDD), re spec tively.6 9-CM had dif fi cul ties in anal y sis, we adopted the grouping sys tem de vel oped by the Na tional Cen ter of Health Study de sign Sta tis tics of the United States for use with the data of the The antilipemic drugs de fined in our study in cluded Na tional Ambu la tory Medi cal Care Survey (NAMCS) all drug items be long ing to the group C10 (se rum lipid and the Na tional Hospi tal Am bu la tory Medi cal Care re duc ing agents) of the ATC clas si fi ca tion sys tem. The Survey (NHAMCS).7 All of the orig i nal ICD-9-CM C10 group had only one 3rd-level sub group C10A (cho- codes were re clas si fied into 22 main cat e go ries and 194 lesterol- and triglyceride re duc ers) with five 4th-level groups. Be side cal cu lat ing the crude rates of ma jor con- subgroups: C10AA (HMG CoA reductase inhib i tors), com i tant diseases in the patients receiv ing antilipemic C10AB (fibrates), C10AC (bile acid sequestrants), C10AD drugs, we also com puted the stan dard ized mor bid ity ra- (nic o tinic acid and de riv a tives), and C10AX (other cho- tios (SMR) (the in di rect method of rate adjust ment) to les terol- and triglyceride re duc ers). Totally, 145 items of elim i nate the con found ing ef fect from age fac tor.8

40 Jan u ary 2003 Antilipemic Drug Use in Tai wan

Data pro cess ing and sta tis ti cal anal y sis lence rates was sim i lar in both sexes. Al though the to tal The da ta base software of Microsoft SQL Server num ber of pa tients with antilipemic ther apy was larger in 2000 was used for data link age and cal cu la tion. For the male than that in fe male, the female patients still out - age- and sex-specific prev a lence, the de nom i na tors were num bered the male pa tients be fore the age of 49 years. those people who were still insured un der the NHI in In the out pa tient claims of the co hort in 2000, there 2000. Among the 50,000 peo ple of the sam pling co hort, were 74 dif fer ent drug items of antilipemic drugs with 18 46,614 were still in sured in 2000. In cal cu lat ing the num- main in gre di ents. Al though atorvastatin (C10AA05) has bers of DDDs per 1,000 in hab it ants per day for each kind been avail able within the NHI since No vem ber 2000, it of antilipemic drugs, the to tal num bers of DDDs from the did not ap pear in our co hort dataset. The antilipemic drugs cohort were at first di vided by 46,614 (people in sured had been prescribed totally 3,850 times with 70,272 un der the NHI at the end of 2000) and 366 (days in year DDDs (Ta ble 2). On an av er age, a pa tient with anti lipemic 2000), and then mul ti plied by 1,000 (in hab it ants). In cal- ther apy re ceived 5.1 (SD 4.5) prescrip tions of anti - cu lat ing the SMR, the stan dard pop u la tion was also the lipemic drugs in one year, where a pre scrip tion con tained co hort. The prev a lence rates and SMRs were dis played 18.3 (SD 11.5) DDDs. Be sides, we mea sured 4.1 DDDs with 95% con fi dence in ter vals.9 per 1,000 in hab it ants per day for all antilipemic drug use in 2000. The statins and fibrates pre dom i nated the antilipemic drug use. While gemfibrozil was most pop u lar in RESULTS re spect of re cip i ents and pre scrip tion items, simvastatin had the larg est amount of use in unit of DDDs. Among the co hort with 46,614 peo ple who were still In 2000, the cohort in our study had 657,038 visits in sured un der the NIH in 2000, only 41,333 (88.7%) peo- where 901,977 di ag nos tic codes with 6,335 dis tinct di ag- ple had the out pa tient visit of West ern med i cine within no ses had been speci fied. The 760 patients with the NHI dur ing the whole year. Antilipemic drugs had antilipemic ther apy had 24,240 vis its where 44,320 di ag- been ever prescribed to 760 people (Ta ble 1). The to tal nostic codes with 1,752 distinct diag no ses had been prev a lence of antilipemic drug use was 1.6% (95% CI: spec i fied. Ta ble 3 lists the top 12 di ag no sis groups that 1.5% to 1.7%). Nearly a half of the pa tients with anti- were most fre quently ob served in the patients with lipemic therapy were more than 60 years of age. The antilipemic ther apy. In or der to il lus trate the SMRs, the age-specific prev a lence rate jumped af ter the age of 40 fre quen cies of these diag no ses among the cohort were years and was the high est in the age group of 60-69 years also dis played. Di a be tes mellitus co-existed in 37.8% of (7.2%). The prev a lence rate in the age group over 70 the patients with antilipemic ther apy and the SMR was years was higher than that in the age group of 50 - 60 3.34 (95% CI: 2.61 to 4.17). The other sig nif i cant con- years (6.0% vs. 4.5%). The trend of age-specific prev a - com i tant diseases included other en do crine nutri tional

Table 1. Age-sex distribution of the sampling cohort, and patients receiving the antilipemic therapy Age (years) Sampling cohorta Patients with antilipemic therapy Prevalence of antilipemic therapy(95% confidence intervals) Total Male Female Total Male Female Total Male Female 0 - 9 6486 (13.91%) 3368 3118 6 (0.79%) 2 4 0.1% (0.0%, 0.2%) 0.1% (0.0%, 0.2%) 0.1% (0.0%, 0.3%) 10 - 19 7106 (15.24%) 3587 3518 3 (0.39%) 1 2 0.0% (0.0%, 0.1%) 0.0% (0.0%, 0.2%) 0.1% (0.0%, 0.2%) 20 - 29 8116 (17.41%) 4028 4088 13 (1.71%) 5 8 0.2% (0.1%, 0.3%) 0.1% (0.0%, 0.3%) 0.2% (0.1%, 0.4%) 30 - 39 8075 (17.32%) 4104 3971 48 (6.32%) 14 34 0.6% (0.4%, 0.8%) 0.3% (0.2%, 0.6%) 0.9% (0.6%, 1.2%) 40 - 49 7179 (15.40%) 3530 3649 137 (18.03%) 47 90 1.9% (1.6%, 2.2%) 1.3% (1.0%, 1.8%) 2.5% (2.0%, 3.0%) 50 - 59 3920 (8.41%) 1920 2000 175 (23.03%) 98 77 4.5% (3.8%, 5.1%) 5.1% (4.1%, 6.2%) 3.9% (3.0%, 4.8%) 60 - 69 3014 (6.47%) 1493 1521 216 (28.42%) 140 76 7.2% (6.2%, 8.1%) 9.4% (7.9%, 10.9%) 5.0% (3.9%, 6.3%) > = 70 2718 (5.83%) 1468 1250 162 (21.32%) 104 58 6.0% (5.1%, 6.9%) 7.1% (5.8%, 8.4%) 4.6% (3.5%, 6.0%) Total 46614 (100.00%) 23498 23115 760 (100.00%) 411 349 1.6% (1.5%, 1.7%) 1.7% (1.6%, 1.9%) 1.5% (1.4%, 1.7%) a The status of sex was unknown in one insured.

41 Tzeng-Ji Chen et al. Jour nal of the Chi nese Med i cal As so ci a tion Vol. 66, No. 1

Table 2. Distribution of antilipemic drug prescriptions by main ingredients No of No of antilipemic Total DDDsb of DDDs per 1,000 ATCa coding Group/ingredient name recipients drug items antilipemic drugs inhabitants per day C10AA HMG CoA reductase inhibitors 422 1,934 40,552 2.4 C10AA01 Simvastatin 170 753 19,115 1.1 C10AA02 Lovastatin 134 475 8,634 0.5 C10AA03 Pravastatin 70 348 4,963 0.3 C10AA04 Fluvastatin 88 358 7,840 0.5 C10AB Fibrates 395 1,700 24,850 1.5 C10AB01 Clofibrate 12 49 247 0.0 C10AB02 Bezafibrate 80 347 5,123 0.3 C10AB03 Aluminium clofibrate 1 4 90 0.0 C10AB04 Gemfibrozil 260 1,017 14,648 0.9 C10AB05 Fenofibrate 33 90 2,285 0.1 C10AB06 Simfibrate 1 1 2 0.0 C10AB09 Etofibrate 39 192 2,455 0.1 C10AC Bile acid sequestrants 7 26 337 0.0 C10AC01 Cholestyramine 4 20 189 0.0 C10AC03 Detaxtran 3 6 148 0.0 C10AD Nicotinic acid and derivatives 34 172 4,384 0.3 C10AD01 Niceritrol 2 16 148 0.0 C10AD03 Nicofuranose 5 15 262 0.0 C10AD06 Acipimox 21 113 3,311 0.2 C10AD- Nicomol 6 28 663 0.0 C10AX Other cholesterol and triglyceride reducers 6 18 148 0.0 C10AX02 Probucol 6 18 148 0.0 Total 760c 3,850 70,272 4.1 a ATC = Anatomical Therapeutic Chemical classification system. b DDD = defined daily dose. c Among 760 patients, 153 patients had received more than one kind of antilipemic drugs during the year 2000. and met a bolic dis eases im mu nity dis or ders (rate: 25.1%, Program Expert Panel on Detec tion, Eval u a tion, and SMR: 3.01), es sen tial hy per ten sion (rate: 48.8%, SMR: Treatment of High Blood Choles terol in Adults.10 Al - 2.40), and other heart dis ease (rate: 30.7%, SMR: 2.36). though the prev a lence of antilipemic drug use might be sig nif i cantly lower than the prev a lence of hyperlipi - demia among the pop u la tion, the trend and other anal y- DISCUS SION ses would help to iden tify the key points of pub lic health and med i cal in ter ven tions. The in sur ance claims data from the NHI in Tai wan The Chi nese in Tai wan are known to have low in ci- are in valu able to the re search of pharmacoepidemiology. dence of cor o nary ar tery dis ease and low prev a lence of The uti li za tion of antilipemic drugs is one of the good ex- hyperlipidemia in in ter na tional com par i son.11 But it re - am ples be cause nearly all of these drugs have unique in- mains un known whether the prev a lence of pa tients with dica tion and the pre scrip tion of them has been un der antilipemic therapy in Tai wan is also low cor re spond- rigid re stric tions based on the rec og nized guide lines,e.g. ingly. The in ter na tional com par i son of drug uti li za tions the sec ond re port of the Na tional Cho les terol Ed u ca tion is usu ally more dy namic than that of dis ease ep i de mi ol-

42 Jan u ary 2003 Antilipemic Drug Use in Tai wan

Table 3. Frequency of concomitant diseases in the patients with antilipemic therapy Diagnosis grouping Sampling cohort Patients with antilipemic therapy (n = 46,614) (n = 760) No. of patients No. of patients with a diagnosis Rate with a diagnosis Rate SMRa (95% CIb) Other acute respiratory infections 30,562 65.6% 526 69.2% 1.14 (0.95, 1.35) Essential hypertension 3,011 6.5% 371 48.8% 2.40 (1.94, 2.92) Other diseases of the digestive system 10,466 22.5% 362 47.6% 1.55 (1.25, 1.89) Diseases of the teeth and supporting structures 15,949 34.2% 294 38.7% 1.23 (0.96, 1.53) Diabetes mellitus 1,796 3.9% 287 37.8% 3.34 (2.61, 4.17) Other heart disease 2,019 4.3% 233 30.7% 2.36 (1.80, 3.02) Conjunctivitis 8,432 18.1% 218 28.7% 1.27 (0.95, 1.64) Other symptoms/signs and ill-defined conditions 4,656 10.0% 202 26.6% 1.63 (1.21, 2.12) Other dorsopathies 3,921 8.4% 196 25.8% 1.46 (1.08, 1.91) Acute bronchitis and bronchiolitis 10,106 21.7% 193 25.4% 1.25 (0.92, 1.63) Other endocrine nutritional and metabolic diseases immunity disorders 1,971 4.2% 191 25.1% 3.01 (2.21, 3.94) Gastritis and duodenitis 5,174 11.1% 159 20.9% 1.39 (0.99, 1.87) a SMR = standardized morbidity ratio. The age adjustment was preformed according to the age structure of the sampling cohort. b CI = confidence intervals. ogy. For ex am ple, the Fin land and other Nordic coun tries would per form an other study to know what per cent age of had slightly lower prev a lence of antilipemic drug us ers pa tients with di a be tes mellitus or es sen tial hy per ten sion and fewer DDDs/1,000 inhab it ants/day in early 1990s also re ceive antilipemic ther apy. than Tai wan in 2000.2,3 How ever, the antilipemic drug As to the varia tions of phy si cians in man ag ing use in those coun tries in creased 6- to 8-fold from 1994 to hyperlipidemia or pre scrib ing the antilipemic drugs, the 2000, mostly due to statins.4 Fur ther study is needed to NHIRD did not sup ply datasets sampled accord ing to in ves ti gate whether the strict re stric tions within the NHI con sult ing phy si cians. The datasets in our cur rent study in Tai wan, e.g. man da tory blood anal y sis in three-month and other avail able datasets with system atic sam pling in ter vals, dis cour age the antilipemic drug use and hin der from all vis its could only of fer ag gre gate sta tis tics of the the dif fu sion of newer in no va tions. phy si cian spe cial ties, not of in di vid ual phy si cians. The focus of pharmacoepidemiology study of anti - A se ri ous draw back of the NHI claims is the ab sence lipemic drugs in the lit er a ture could be sum ma rized into of lab o ra tory data, let alone other clin i cal and so cio eco- the fol low ing aspects: age-, sex-, dis ease-, physi cian- nomic infor ma tion. Further more, the pri vacy policy of specific drug use, and out come anal y sis.12-21 Some of the BNHI and NHIRD has en crypted the pa tients’ per- these inves ti ga tions could be also re peated in Tai wan sonal identi fi ca tion num bers (PID). Al though the en - with the cur rent NHIRD datasets, but the other could not crypted PIDs re main con sis tent in all the NHIRD datasets, be done be cause of the in her ent lim i ta tions of the NHI they can not be linked to other out side da ta bases, e.g. the claims data. mor tal ity da ta base of the De part ment of Health. Be sides, For ex am ple, hyperlipidemia, hy per ten sion and hy- the re search ers are for bid den to iden tify the pa tients for per glycemia (so-called 3H) are known to have a clus ter- dis ease confir ma tion and follow-ups. That is, the out - ing tendency. Using SMRs to com pare the patients re - come anal y sis and the study on the appro pri ate ness ceiving antilipemic therapy with the sam pling pop u la- (over- and undertreatment) of antilipemic drug use are tion in comorbidity, our study showed that those pa tients not fea si ble with the NHI claims.22-25 in Tai wan did have con com i tant di a be tes mellitus and es- To the best of our knowledge, our current study sential hy per ten sion more fre quently. In the future we might be one of the first inves ti ga tions con cern ing the

43 Tzeng-Ji Chen et al. Jour nal of the Chi nese Med i cal As so ci a tion Vol. 66, No. 1 prev a lence of antilipemic drug use among a rep re sen ta- 143). Hyattsville: Na tional Cen ter for Health Sta tis tics, 1999. tive pop u la tion in Tai wan. Be cause the pri vate use of the 8. Page RM, Cole GE, Timmreck TC. Ba sic Ep i de mi o log i cal drugs out side the NHI is not in cluded in our datasets and Methods and Biostatistics: A Prac ti cal Guide book. Boston, the claims fail to of fer other sig nif i cant data, the tra di- Lon don: Jones and Bart lett, 1995. 9. Gardner MJ, Altman DG. Sta tis tics with Con fi dence - Con fi- tional ep i de mi o log i cal sur veys are still needed to fa cil i- dence In ter vals and Sta tis ti cal Guide lines. Lon don: Brit ish tate the under stand ing of hyperlipidemia man age ment Med i cal Jour nal, 1989. and antilipemic drug use in Tai wan.26 10. Ex pert Panel on De tec tion, Eval u a tion, and Treat ment of High Blood Cho les terol in Adults. Sum mary of the sec ond re port of the Na tional Cho les terol Ed u ca tion Pro gram (NCEP) Ex pert ACKNOWL EDGE MENTS Panel on De tec tion, Eval u a tion, and Treat ment of High Blood Choles terol in Adults (Adult Treat ment Panel II). JAMA This study is based in part on data from the Na tional 1993;269:3015-23. Health In sur ance Re search Da ta base pro vided by the Bu- 11. Pan WH, Chiang BN. Plasma lipid pro files and ep i de mi ol ogy reau of Na tional Health In sur ance, De part ment of Health of atherosclerotic dis eases in Tai wan - a unique ex pe ri ence. and man aged by Na tional Health Re search In sti tutes in Athero scle ro sis 1995;118:285-95. Taiwan. The inter pre ta tion and con clu sions contained 12. Sketris IS, Kephart GC, Hicks VA, Hub bard EJ, Brown MG, Chan dler RF, MacLean DR. Pre scribing pat terns of antilipemic herein do not repre sent those of Bu reau of Na tional drugs and prev a lence of hy per cho les ter ol emia in the Nova Health Insur ance, Depart ment of Health or Na tional Sco tia pop u la tion more than 65 years old. Ann Pharmacother Health Re search In sti tutes. 1995;29:576-81. 13. Miller M, Byington R, Hunninghake D, Pitt B, Furberg CD. Sex bias and underutilization of lipid-lowering ther apy in pa- REFER ENCES tients with cor o nary ar tery dis ease at ac a demic med i cal cen- ters in the United States and Can ada. Arch Intern Med 1. Scan di na vian Simvastatin Sur vival Study Group. Ran dom ised 2000;160:343-7. trial of cho les terol low er ing in 4444 pa tients with cor o nary 14. Savoie I, Kazanjian A. Uti li za tion of lipid-lowering drugs in heart dis ease: the Scan di na vian Simvastatin Sur vival Study men and women: a re flec tion of the re search ev i dence? J Clin (4S). Lancet 1994;344:1383-9. Epidemiol 2002;55:95-101. 2. Martikainen J, Klaukka T, Reunanen A, Peura S, Wahlroos H. 15. Massing MW, Sueta CA, Chowdhury M, Biggs DP, Simpson Re cent trends in the con sump tion of lipid-lowering drugs in RJ Jr. Lipid man age ment among cor o nary ar tery dis ease pa- Fin land. J Clin Epidemiol 1996;49:1453-7. tients with di a be tes mellitus or ad vanced age. Am J Cardiol 3. Magrini N, Einarson T, Vaccheri A, McManus P, Montanaro 2001:87:646-9. N, Berg man U. Use of lipid-lowering drugs from 1990 to 16. Jackevicius CA, An der son GM, Leiter L, Tu JV. Use of the 1994: an in ter na tional com par i son among Aus tra lia, Fin land, statins in pa tients af ter acute myo car dial in farc tion: Does ev i- It aly (Emilia Romagna Re gion), Nor way and Swe den. Eur J dence change prac tice. Arch In tern Med 2001;161:183-8. Clin Pharmacol 1997;53:185-9. 17. Harder S, Mohr O, Klepzig H. Lipid-lowering treat ment in 4. OECD Health Data 2001. Paris: OECD (Or gani sa tion for cor o nary ar tery dis ease: a sur vey in an am bu la tory out pa tient Eco nomic Co-operation and De vel op ment), 2001. clinic. Int J Clin Pharmacol Ther 2001;39:534-8. 5. Su TP, Chen TJ, Hwang SJ, Chou LF, Fan AP, Chen YC. Uti li- 18. Stafford RS, Blumenthal D, Pasternak RC. Vari a tions in cho- za tion of psychotropic drugs in Tai wan: I. an over view of out- les terol man age ment prac tices of U.S. phy si cians. J Am Coll pa tient sec tor in 2000. J Chin Med Assoc 2002;65:378-91. Cardiol 1997;29:139-46. 6. Guide lines for ATC Clas si fi ca tion and DDD As sign ment, 3rd 19. Baxter C, Jones R, Corr L. Time trend anal y sis and vari a tions ed. Oslo: WHO Col lab o rating Cen tre for Drug Sta tis tics in pre scrib ing lipid low er ing drugs in gen eral prac tice. BMJ Meth od ol ogy, 2000. 1998;317:1134-5. 7. Schappert SM. Am bu la tory Care Visits to Phy si cian Of fices, 20. Packham C, Rob in son J, Mor ris J, Rich ards C, Marks P, Gray Hos pi tal Out pa tient De part ments, and Emer gency De part ments: D. Statin prescrib ing in Nottingham gen eral prac tices: a United States, 1997 (Vi tal Health Sta tis tics, Se ries 13, No. cross-sectional study. J Pub lic Health Med 1999;21:60-4.

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21. Pearson TA, Laurora I, Chu H, Kafonek S. The Lipid Treat- mark and Bo lo gna, It aly. Br J Clin Pharmacol 2000;49: 463-71. ment As sess ment Pro ject (L-TAP): a multicenter sur vey to 24. Feely J, McGettigan P, Kelly A. Growth in use of statins af ter eval u ate the per cent ages of dyslipidemic pa tients re ceiv ing tri als is not targeted to most ap pro pri ate pa tients. Clin lipid-lowering ther apy and achiev ing low-density li po pro tein Pharmacol Ther 2000;67:438-41. cho les terol goals. Arch In tern Med 2000;160:459-67. 25. Abookire SA, Karson AS, Fiskio J, Bates DW. Use and mon i- 22. Majumdar SR, Gurwitz JH, Soumerai SB. Undertreatment of tor ing of “statin” lipid-lowering drugs com pared with guide- hyperlipidemia in the sec ond ary pre ven tion of cor o nary ar tery lines. Arch In tern Med 2001;161:53-8. dis ease. J Gen In tern Med 1999;14:711-7. 26. Lee YT, Lin RS, Sung FC, Yang CY, Chien KL, Chen WJ, et 23. Larsen J, Vaccheri A, Andersen M, Montanaro N, Berg man U. al. Chin-Shan Com mu nity Car dio vas cu lar Co hort in Tai wan - Lack of ad her ence to lipid-lowering drug treat ment. A com par i- base line data and five-year fol low-up mor bid ity and mor tal ity. son of uti li za tion pat terns in de fined pop u la tions in Funen, Den- J Clin Epidemiol 2000;53:838-46.