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
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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
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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
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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.
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