The use of antihypertensive therapy in Spain (1986-1994)

The Use o An ihype ensi e The apy in Spain (1986–1994) Naja y Suliman Jaba y, Alicia Mendiluce He e o, and Ja ie Al a ez Gonzalez We aimed o analyze he ends in an ihype ensi e he apy in Spain du ing he pe iod 1986 o 1994, as well as he change in he pa e n o di e en d ugs, in ela ion o di e en na ional/in e na ional ecommenda ions o hype ension ea men . An ihype ensi e consump ion was s udied using he de ined daily dose (DDD) and he DHD (DDD/1000 inhabi an s/ day) o each d ug, as de ined by he D ug U iliza ion Resea ch G oup o he Eu opean O ice o he Wo ld Heal h O ganiza ion. The ana omical classi ica ion o hypo ensi e d ugs has been made acco ding o EPhMRA (Eu opean Pha maceu ical Ma ke Associa ion) guidelines. A signi ican inc ease o 117.4% (41.39/90 DHD) in an ihype ensi e d ug consump ion was obse ed in he pe iod 1986 o 1994. In 1986 diu e ics we e he mos consumed (30.27 DHD), ollowed by calcium an agonis s (5.37), ␤ -blocke s (3.93), and he angio ensin-con e ing enzyme (ACE) inhibi o (1.37). In 1994 ACE inhibi o s, calcium an agonis s, and ␤ -blocke s inc eased signi ican ly (P<< .0001), whe eas diu e ics we e s ill he mos commonly p esc ibed. Ni edipine and cap op il we e he mos used among calcium an agonis s and ACE inhibi o s. Na ional and in e na ional ecommenda ions had no e ec on p esc ip ion pa e ns. An ihype ensi e he apy o all ypes is inc easing in Spain. Diu e ics emain he mos popula , ␤ -blocke s s ay s able, whe eas he newe ypes a e ising apidly. Na ional and in e na ional ecommenda ions had no e ec on p esc ip ion pa e ns. Am J Hype ens 2000;13:607–610 © 2000 Ame ican Jou nal o Hype ension, L d. KEY WORDS: Hype ension, hypo ensi e d ug consump ion, p esc ip ion pa e n. O e he las 20 yea s 1–5 an inc ease o he use o an ihype ensi e d ugs has been obse ed in he de eloped coun ies. In Spain, an inc ease o mo e han 100% was desc ibed be ween 1981 and 1990. 1 These ac s can be explained by an imp o ed awa eness and ea men o hype ensi e disease 6,7 ; g ea public heal h demand, as almos 100% o he Spanish popula ion a e co e ed by he Na ional Heal h Se ice; changing ecommen- da ions on he de ec ion, e alua ion, and ea men o high blood p essu e 7–10 ; and he disco e y ha ea - men o hype ension educes ca dio ascula isks. 11 In he 1970s, changes in hype ensi e d ugs we e e- co ded, ␤ -blocke s, diu e ics, and cen al sympa- holi ic being he mos p esc ibed d ug ea men s. 2,5 In he las decade, he consump ion o diu e ics and ␤ -blocke s has no declined, while he e has been a spec acula inc ease wi h espec o angio ensin-con- e ing enzyme (ACE) inhibi o s and calcium an ago- nis s, and an almos o al disappea ance o cen al sympa holi ic d ugs. 2–4,12,13 In he opinion o some w i e s, hese changes ha e no co ela ion wi h na- ional o in e na ional ecommenda ions o hype en- si e ea men , 4,13 whe eas o he s ake he iew ha Recei ed Janua y 8, 1999. Accep ed Oc obe 25, 1999. F om he Hype ension Uni (Neph ology Depa men ), and Pha macology Depa men , Uni e si y Hospi al, Valladolid, Spain. Add ess co espondence and ep in eques s o P o . Naja y Suliman Jaba y, Se icio de Ne ologia, Hospi al Uni e si a io, C/Ramon y Cajal no. 3, 47011 Valladolid, Spain; e-mail: jaba y@ .u a.es AJH 2000;13:607–610 © 2000 by he Ame ican Jou nal o Hype ension, L d. 0895-7061/00/$20.00 Published by Else ie Science, Inc. PII S0895-7061(99)00261-7 Downloaded om h ps://academic.oup.com/ajh/a icle/13/6/607/186399 by Biblio eca Uni e si a ia.Facul ad de Medicina use on 09 Decembe 2021 empo al pa e ns in he use o hypo ensi e d ugs a e ela ed o inc eased clinical ials 14 and he e ec i e- ness o pha maceu ical p omo ional p ac ices. 15–17 The objec i e o his s udy was o desc ibe he ends in an ihype ensi e d ug use in Spain om 1986 h ough 1994, as well as hei changing pa e ns, and hei co ela ion wi h na ional/in e na ional ec- ommenda ions on hype ensi e ea men . MATERIALS AND METHODS In ca ying ou his s udy on he use o an ihype en- si e d ugs in Spain, we ha e used he ana omical classi ica ion o he Eu opean Pha maceu ical Ma ke Resea ch Associa ion (EPhMRA). The s udy includes all hypo ensi es dispensed h ough he Spanish Na- ional Heal h Se ice om 1986 o 1994, on he basis o he ECOM da a base, which has been in ope a ion since 1981. This da abase includes comple e in o ma- ion wi h ega d o he dispensing o pha maceu icals in pha macies. Such in o ma ion is a ailable in au o- ma ed o m, aking in o accoun he bills o all he p esc ip ions issued by he Na ional Heal h Se ice, which co e s almos 100% o he Spanish popula ion. The da a was p o ided by he Subdi eccio´n Gene al de O denacion y Asis encia Fa mace´u ica, o he Di- eccio´n Gene al de Fa macia y P oduc os Sani a ios o he Minis e io de Sanidad y Consumo, in he o m o numbe s o uni s sold, pha maceu ical o m (capsules o pills), and composi ion. We ha e calcula ed he DHD (see below) on he basis o hese da a. I should be s essed ha many o hese pha macologic sub- g oups, and in pa icula diu e ics and ␤ -blocke s, a e used in o he pa hologies such as ischemic hea dis- ease o conges i e hea ailu e, gi en ha he Spanish da abase does no ake in o accoun diagnos ic indica- ions. The DHD exp esses an ihype ensi e consump ion (DDD [de ined daily dose]/1000 inhabi an /day) and is used o quan i y d ug consump ion. The DDD o each d ug is de ined by The D ug U ilisa ion Resea ch G oup o he Eu opean O ice o he Wo ld Heal h O ganiza ion (WHO), which publishes a lis o he di e en DDD d ugs including hypo ensi es. 18 The DDD is e y use ul as an in e na ional compa a i e uni , as i allows compa isons be ween di e en coun- ies and pe iods o ime wi hou aking in o accoun p ices o uni doses. 19 The DHD is calcula ed acco ding o he o mula: UV ⫻FF/E⫻C/FF ⫻1000inh DDD ⫻inh. no. ⫻365 days whe e UV is he uni o d ugs sold, FE/E is he num- be o able s o each box, C/FF is he composi ion o each d ug, and Inh is he inhabi an . We used SPSS-PC o da a analysis. All da a a e exp essed as means ⫾SEM; linea eg ession analysis was used o exp ess he di e ences in he use o d ugs be ween di e en pe iods; ⫽co ela ion coe icien and P⬍.05 was conside ed s a is ically signi ican . RESULTS Ou esul s show a 117.4% (41.39/90 DHD) inc ease in he consump ion o an ihype ensi e d ugs be ween 1986 and 1994 (Figu e 1). In 1986, diu e ics we e he mos consumed an ihype ensi e d ugs (30.27 DHD), TABLE 1. TRENDS IN ANTIHYPERTENSIVE DRUG USE (IN DHD), 1986 TO 1994 D ug 1986 1987 1988 1989 1990 1991 1992 1993 1994 P ACEI 1.3 2.4 4.5 7.6 11.2 14.6 18.6 21.9 24.7 0.9871 .0001 CA 5.3 7.5 8.9 10.8 13 15.2 17 19.3 22.3 0.9947 .0001 D 30.2 32.5 35.6 35.6 35.4 35 34.9 34.6 35.5 0.4024 .66 ␤ B 3.9 4.4 5 5.6 5.9 6.1 6.3 6.3 6.6 0.9178 .0001 ␣ B 0.4 0.4 0.39 0.3 0.3 0.31 0.48 0.6 0.7 0.3316 .10 ␣␤ B 0.01 0.01 0.01 0.0 0.0 0.008 0.009 0.009 0.01 0.7306 .003 ACEI ⫽angio ensin-con e ing enzyme inhibi o , CA ⫽calcium an agonis , D ⫽diu e ics, ␤ B⫽ ␤ -blocke s, ␣␤ ⫽ ␣ -blocke s, ␣␤ B⫽ ␣␤ -blocke s. ⫽co ela ion coe icien ; P⫽s a is ically signi ican . FIGURE 1. T ends in an ihype ensi e d ug use (in DHD), 1986 o 1994 (lineal eg ession). AJH–JUNE 2000–VOL. 13, NO. 6, PART 1608 JABARY ET AL Downloaded om h ps://academic.oup.com/ajh/a icle/13/6/607/186399 by Biblio eca Uni e si a ia.Facul ad de Medicina use on 09 Decembe 2021 ollowed by calcium an agonis (5.37 DHD), ␤ -block- e s (3.93 DHD), and ACE inhibi o s (1.37 DHD) (Table 1).O e a 9-yea pe iod, use o ACE inhibi o s, calcium an agonis s, and ␤ -blocke s inc eased signi ican ly (P⬍.0001) (24.76, 22.36, 6.64 DHD), while diu e ics we e s ill he mos commonly p esc ibed and expe i- enced a small bu no signi ican inc ease (Table 1). The emaining g oup ( ␣ - and ␣␤ -blocke s) did no show a signi ican change o e he same pe iod. Wi hin he calcium an agonis g oup, ni edipine was he mos used, ollowed by e apamil, wi h a spec acula inc ease o amlodipine (Figu e 2). Cap o- p il emained he mos -used ACE inhibi o , ollowed by enalap il, ano he ACE inhibi o g oup s ill a behind cap op il (Figu e 3). DISCUSSION Ou esul s show a e y high inc ease in he use o an ihype ensi e agen s in Spain, which has doubled in he las decade. We no ed a change in he use o he di e en hypo ensi e g oups, wi h an inc eased use o new ones such as ACE inhibi o s and calcium an ag- onis s, which became he mos commonly p esc ibed a e diu e ics. 2–4 Ou esul s a e impo an because hey co e he consump ion o an ihype ensi e d ugs wi hin he o al Spanish popula ion. Howe e , i is no possible o es ablish whe he hese d ugs a e used o hype ension o o o he diseases, such as ca diac ailu e, ischemic hea disease, o diabe ic neph opa- hy, as he Spanish da a do no include diagnos ic indica ions. Ne e heless, we emain con inced o he impo ance o hese da a, as in mos cases he mos equen indica ion is hype ension. The use o DDD no only allows o he de ini ion o d ug consump ion, bu also o i s compa ison wi h o he coun ies. In 1984 he use o p azosin in No way was 5.5 DDD/1000 inhabi an s/day, 20 whe eas in Spain i was 0.28 DDD/1000 inhabi an s/day. 1 Ou s udy co e s a long ime pe iod compa ed wi h o h- e s, 4,12,13 which a e o sho e pe iods, wo k wi h smalle popula ions, 3,21,22 o s udy some, bu no all, an ihype ensi e d ugs. 22 We conside ha he inc ease in an ihype ensi e consump ion is ela ed o a majo heal h demand, o he ac ha he Spanish Na ional Heal h Se ice is ee, and o an imp o ed awa eness and ea men o he Spanish hype ensi e popula ion. 6 Psa y e al 14 epo a empo al inc ease in diu e ics and ␤ -blocke s and dec ease in use o ACE inhibi o s and calcium an agonis s ela ed o majo clinical ials on hype ension ea men , 23–25 which show ha he use o low doses o diu e ics educes ca dio ascula isk. We ha e no ound his empo al ela ion, as he consump ion o diu e ics was he same be ween 1989 and 1992 (35 DHD). Na ional and in e na ional ecommenda ions o ea men o high blood p essu e had li le e ec on p esc ibing pa e ns, 4,13 as we ha e seen in ou esul s. The e a e se e al possible easons o his: he a ac- i eness o using new he apies so ha p ac i ione s a e conside ed up- o-da e; he ac ha clinicians may be disappoin ed wi h he esul s o clinical ials; he ac ha many hype ensi e pa ien s also su e om o he diseases (diabe es melli us, ischemic hea dis- eases, gou , e c.) whe e he new d ugs ha e speci ic indica ions, and inally he e ec i eness o pha ma- ceu ical p omo ional p ac ices. 15–17 The cos implica ions o hese p ac ice pa e ns a e eno mous. The es ima ed wholesale cos o an ihy- pe ensi e d ugs in 1996 in Spain is $106 million, ep esen ing 2% o all d ug consump ion. 26 In 1995 consump ion o calcium an agonis s in he US was $2.67 billion and $1.67 o ACE inhibi o s, whe eas he cos o diu e ics and ␤ -blocke s was $168 million and $433 million, espec i ely. 27 Gi en ha in 1995 cal- FIGURE 2. T ends in calcium an agonis use (in DHD), 1986 o 1994 FIGURE 3. T ends in ACE inhibi o use (in DHD), 1986 o 1994 AJH–JUNE 2000–VOL. 13, NO. 6, PART 1 ANTIHYPERTENSIVE THERAPY IN SPAIN 609 Downloaded om h ps://academic.oup.com/ajh/a icle/13/6/607/186399 by Biblio eca Uni e si a ia.Facul ad de Medicina use on 09 Decembe 2021 cium an agonis use ep esen ed 38% o p esc ip ions o ca dio ascula disease in communi y e ail pha - macies, compa ed wi h 8% o diu e ics, he po en ial sa ings om a change in hype ensi e p esc ibing pa e ns could amoun o hund eds o millions o dolla s. REFERENCES 1. Ma ı´n A ias L (eds.): D ug Consump ion in Spain. Sec e a ia de Publicaciones Uni e sidad, Valladolid, 1994. 2. G oss TP, Wise RP, Knapp DE: An ihype ensi e d ug use. T ends in he Uni ed S a es om 1973 o 1985. Hype ension 1989;13(5 suppl):I113–I118. 3. Rolland F, La on J, Mon as uc JL, Mon as uc P: De- elopmen o an ihype ensi e d ug consump ion in he Toulouse Uni e si y Regional Hospi al Cen e om 1981 o 1989. The apies 1991;46(I):45–48. 4. Siegel D, Lopez J: T ends in an ihype ensi e d ug use in he Uni ed S a es: do he JNC V ecommenda ions a ec p esc ibing? Fi h Join Na ional Commi ee on he De ec ion, E alua ion, and T ea men o High Blood P essu e. JAMA 1997;278(21):1745–1748. 5. Hu ley SF, Williams SL, McNeil JJ: T ends in p esc ib- ing o an ihype ensi e d ugs in Aus alia, 1977–1987. Med J Aus 1990;5:152(5):259–260. 6. Coca A. Con ol o hype ension in Spain. Resul s o Con olp es 95 s udy. Hype ensio´n 1995;12:182–188. 7. The Join Na ional Commi ee On P e en ion, De ec- ion, E alua ion, and T ea men o High Blood P es- su e: The Six h Repo . A ch In e n Med 1997;157:2413– 2446. 8. The Join Na ional Commi ee On P e en ion, De ec- ion, E alua ion, and T ea men o High Blood P es- su e. The 1988 Repo : A Co-ope a i e s udy. A ch In e n Med 1988;148:1023–1038. 9. The Join Na ional Commi ee On P e en ion, De ec- ion, E alua ion, and T ea men o High Blood P es- su e. The Fi h Repo : A Co-ope a i e s udy. A ch In e n Med 1993;153:154–183. 10. 1993 guidelines o he managemen o mild hype en- sion: memo andum om a WHO/ISH mee ing. J Hy- pe ens 1993;11:903–919. 11. MacMahon S, Pe o R, Cu le J, Collins R, So ie P, Nea on J, Abbo R, Godwin J, Dye A, S amle J: Blood p essu e, s oke and co ona y hea disease. Pa I. P olonged di e ences in blood p essu e: p ospec i e obse a ional s udies co ec ed o he eg ession dilu- ion bias. Lance 1990;335:765–774. 12. Kawachi I, Malcolm LA, Pu die G: Va iabili y in an i- hype ensi e d ug he apy in gene al p ac ice: esul s om andom na ional su ey. NZ Med J 1989; 28: 102(870):307–309. 13. Wallenius S, Peu a S, Klaukka T, Ennlund H: Who is using an ihype ensi e d ugs? A p esc ip ion analysis om Finland. Scand J P im Heal h Ca e 1996;14(1):54– 61. 14. Psa y BM, Koepsell TD, Yanez ND, Smi h NL, Manolio TA, Heckbe SR, Bo hani JM, Go diene JS, Ru an GH, Sisco ich DS, Fu be g CD: Tempo a y pa e ns o an ihype ensi e medica ion use among adul s, 1989 h ough 1992. JAMA 1995;273:1436–1438. 15. Soumae i SB: Fac o s in luencing p esc ibing. Aus J Hosp Pha m 1988;18(suppl):9–16. 16. Soume ai SB, McLaughlin TJ, A o n J: Imp o ing d ug p esc ibing in p ima y ca e: a c i ical analysis o he expe imen al li e a u e. Milbank Q 1989;67:268–317. 17. Wilkes MS, Doblin BH, Shapi o MF: Pha maceu ical ad e isemen s in leading medical jou nals: expe s as- sessmen s. Ann In e n Med 1992;116:912–919. 18. Be gamn U, G imsson A, Wahba AHW, Wes e gilm B (eds.): S udies in D ug U ilisa ion. Me hods and Appli- ca ions. WHO Regional O ice o Eu ope, Copenha- gen, 1979. 19. Ga cia In˜es a A: D ug consump ion s udies in Spain, an analysis o pha maco he apeu ical si ua ion, in Ins i- u o Nacional de la Salud (eds): Es udios de u lizacio´n de medicamen os. Ins i u o Nacional de la Salud, Ma- d id, 1988, pp. 27–29. 20. No wegian Medicinal Depo : The D ug Consump ion in No way 1981–1985. No wegian Medicinal Depo , Oslo, 1986, p 91. 21. Lee PK, Li RK, Chan JR, Chan S, Lee SC, Tomlison B, C i chley JA: A p esc ip ion su ey in a hospi al hype - ension ou pa ien clinic. B J Clin Pha macol 1997;44: 577–582. 22. Ro mensch HH, Mendele i ch L, Sil e be g DS, Li on M: P esc ibing pa e n o an ihype ensi e d ugs in he communi y. J Hum Hype ens 1996;(Suppl 3):S169– S172. 23. SHEP Co-ope a i e Resea ch G oup: P e en ion o s oke by an ihype ensi e d ug ea men in olde pe - sons wi h isola ed sys olic hype ension: inal esul s o he Sys olic Hype ension in he Elde ly P og am (SHEP). JAMA 1991;265:3255–3264. 24. Dahlo B, Lindholm LH, Hansson L, Sche s en B, Ek- bom T, Wes e PO: Mo bidi y and mo ali y in he Swedish T ial in Old Pa ien s wi h hype ension (STOP-Hype ension). Lance 1991;338:1281–1285. 25. Medical Resea ch Council Wo king Pa y: Medical Re- sea ch Council ial o ea men o hype ension in olde adul s: p incipal esul s. B Med J 1992;304:405– 412. 26. G upos e apeu´ icos y p incipios ac i os de mayo con- sumo en el Sis ema Nacional de Salud du an e 1996. In o macio´n Te ape´u ica del Sis ema Nacional de Sa- lud. 1997;21:153–156. 27. 1995 D ug Topics Redbook. Medical Economics Pub- lishing, Mon ale, NJ, 1995. AJH–JUNE 2000–VOL. 13, NO. 6, PART 1610 JABARY ET AL Downloaded om h ps://academic.oup.com/ajh/a icle/13/6/607/186399 by Biblio eca Uni e si a ia.Facul ad de Medicina use on 09 Decembe 2021