PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 7: 331±337 (1998)

ORIGINAL REPORT

The Use of Angiotensin Converting Enzyme Inhibitors

in General Practice Ð Appropriate or Inappropriate?
J. P. CONNOLLY MD MRCGP*, B. SILKE MD, MRCP, H. McGAVOCK MD FRCGP AND K. WILSON-DAVIES PhD
The Drug Utilisation Research Unit, Department of Therapeutics and Pharmacology,
The Queen's University of Belfast, Northern Ireland

SUMMARY
Aims Ð To evaluate the pattern of prescribing of angiotensin-converting enzyme (ACE) inhibitors in
general practice, related to the primary clinical diagnosis and concomitant medication.
Design Ð A descriptive survey of general practitioners' prescribing habits, presumptive diagnosis and
patient demography over a period of 2 weeks in April 1994.
Setting Ð A strati®ed quota sample of 22 practices in Northern Ireland.
Results Ð The major clinical indication for the use of ACE inhibitors was essential hypertension
(61.5%) with only a minority usage (19.9%) in congestive heart failure. Co-prescription of drugs with
potential for interaction with angiotensin-converting enzyme inhibitors was not uncommon (16.7%). Of
the 353 patients with a diagnosis of congestive heart failure, only 64 (18.1%) were receiving ACE
inhibitors. The dosages used were lower than recommended for this indication. A signi®cantly higher
proportion of elderly patients with heart failure were prescribed hypnotic drugs (14.7% versus 8.3%;
p 5 0.001) and had the co-existence of insomnia (11.8% versus 6.9%;p 5 0.001) compared to patients
without heart failure.
Conclusions Ð ACE inhibitors were underused in the treatment of congestive heart failure, and
were often prescribed in suboptimal dosages. The frequent concurrent prescription of hypnotics and the
co-existence of insomnia in heart failure may re¯ect this therapeutic strategy. # 1998 John Wiley &
Sons, Ltd.

KEY WORDS Ð ACE inhibitors; general practice; Congestive Heart Failure

INTRODUCTION revealed an under-use of angiotensin-converting

In the treatment of congestive heart failure,
angiotensin-converting enzyme inhibitors have
been shown to: (1) Reduce mortality and hospital-
ization,1±4 (2) improve exercise tolerance5,6 and (3)
improve quality of life.7±9
The cost-e€ectiveness of angiotensin-converting
enzyme inhibitors in the treatment of congestive
heart failure has also been demonstrated.10
However, the long-term e€ects of angiotensin-
converting enzyme inhibitors in the treatment of
hypertension are not known. Some studies have
* Correspondence to: Dr J. P. Connolly, 25 Chatsworth, Bangor,
County Down, Northern Ireland, BT19 7WA Tel: 01247 472226.
enzyme inhibitors in the treatment of heart failure
in a primary care setting.11 The aim of this study is
to describe and evaluate the prescribing of angio-
tensin-converting enzyme inhibitors in primary
care, in particular, the relationship between the
diagnosis and the prescription, the dosage pre-
scribed and the co-prescribing of other drugs.
METHODS
In April 1994, over a period of 2 weeks, the general
practitioners from a strati®ed quota sample of 22
volunteer practices in Northern Ireland recorded
their perceived diagnosis for every prescription
item written, including repeat prescriptions, on

CCC 1053±8569/98/050331±07$17.50 Received 6 November 1997

# 1998 John Wiley & Sons, Ltd. Accepted 7 April 1998
332 J. P. CONNOLLY ET AL.
Fig. 1 Ð A comparison of the demography of all Northern Ireland practices (April 1994) with the demography of
the study practices
specially designed forms. A repeat prescription was
de®ned as a prescription written without a face-to-
face consultation between doctor and patient12,13
and repeat prescriptions were distinguished from
prescriptions written at consultation on the forms.
The age and sex of each patient was also recorded.
House calls and out of hours visits were not
recorded.
The study practices were strati®ed according to
partnership size and area health board. There were
352 practices in Northern Ireland in April 1994,
giving a sampling fraction of 1 in 16. The demo-
graphy of the study practices' lists was representa-
tive of the demography of the Northern Ireland
population (Fig. 1). Preliminary analyses showed
that the study practices were similar to non-study
practices in terms of number if items prescribed,
total costs and costs per 1000 patients.
Drugs were coded using the drug codes of the
Central Services Agency, Belfast and the diagnoses
were coded using the International Classi®cation of
Primary Care.14
All patients who were prescribed angiotensin-
converting enzyme inhibitors were selected from
the database, and analyses of the frequencies
of recorded diagnoses were made. Similarly, all
patients with a diagnosis of hypertension or of
congestive heart failure were selected, and prescrib-
ing patterns for these conditions were evaluated.
The mean prescribed daily dosage was calculated
for each drug by dividing the sum of the prescribed
daily dosages for a given drug by the total number
of items for which a daily dose could be calcu-
lated. The mean prescribed daily dose for each
# 1998 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 7: 331±337 (1998)
angiotensin-converting enzyme inhibitor was then
compared to the De®ned Daily Dosage (DDD) for
that drug.15
RESULTS
An overview of the prescribing of angiotensin-
converting enzyme inhibitors
All patients who were prescribed ACE inhibitors
were selected from the database. In all, 291 items
were prescribed to 288 patients (three patients were
each prescribed two di€erent strengths of the same
preparation on the same prescription). Of these
items 179 (61.5%) were prescribed for hypertension
and 58 (19.9%) were prescribed for congestive
heart failure (Table 1). There was no diagnosis
recorded for 16 items (5.5%).
Of the ACE inhibitors prescribed 172 were repeat
prescriptions, 112 were consultation items and the
information was not recorded for seven items.
Therefore, from the usable data, 60.6% of ACE
inhibitors were repeat prescription items and
39.4% were prescribed at consultation.
Of those who were prescribed ACE inhibitors,
patients with heart failure were signi®cantly older
than hypertensive patients (71.5 versus 60.9 years;
p 5 0.001; Fig. 2). For all patients prescribed ACE
inhibitors, 29 (10.1%) were co-prescribed either a
diuretic containing a potassium supplement or a
potassium sparing diuretic on the same script.
Twenty-two (7.6%) were prescribed a non-steroidal
anti-in¯ammatory drug (NSAID) on the same
script. Three patients were prescribed an ACE
 ACE USAGE IN GENERAL PRACTICE 333

Fig. 2 Ð The age distribution by diagnosis of prescribed angiotensin-converting enzyme inhibitors

inhibitor with an NSAID and either a potassium
sparing diuretic or a diuretic containing potassium
on the same script. Of the 48 (16.7%) patients who
were co-prescribed potassium sparing diuretics,
diuretics with potassium supplements or NSAIDs,
28 were prescribed these drugs as repeats, 17 were
prescribed these drugs at consultation and for three
patients this information was not recorded. There-
fore, from the usable data 62.2% of prescriptions in
which co-prescribing occurred as described above
were repeat prescriptions.
The use of ACE inhibitors in congestive heart failure
A total of 353 patients with a diagnosis of con-
gestive heart failure were identi®ed in the database
(regardless of what drugs were prescribed). Of these
64 (18.1%) were prescribed ACE inhibitors.
The mean prescribed daily dosage of captopril
in patients with heart failure was 50.3 mg per day
(1.0 de®ned daily dosages; Table 2). Of the
37 patients with heart failure who were prescribed
captopril (29.7%) were prescribed 75 mg per day or
more. Three patients (8.1%) were prescribed
100 mg per day, which was the highest dose of
captopril prescribed.
The mean prescribed daily dose of enalapril in
patients with heart failure was 8.8 mg per day (0.4
de®ned daily dosages; Table 2). Of the four patients
with heart failure who were prescribed enalapril
two were prescribed 5 mg per day, one was
prescribed 10 mg per day and one was prescribed
15 mg per day.
The mean prescribed daily dose of lisinopril
in patients with heart failure was 9.2 mg per
day (0.5 de®ned daily dosages; Table 2). Of the
10 patients with heart failure who were prescribed

Table 1 Ð The frequencies of diagnoses recorded for patients who were prescribed angiotensin converting enzyme
(ACE) inhibitors
Diagnosis/reason for Frequency Percentage of all diagnoses recorded for Cumulative
encounter patients taking ACE inhibitors percentage
Hypertension 179 61.5 61.5
Heart failure 58 19.9 81.4
No diagnosis recorded 16 5.5 86.9
Ischaemic heart disease 11 3.8 90.7
Hypertension with end 11 3.8 94.5
organ damage
Angina pectoris 7 2.4 96.9
Post myocardial infarction 5 1.7 98.6
Ankle swelling 1 0.3 99.0
Atrial ®brillation 1 0.3 99.3
Renal failure 1 0.3 99.7
Nephrotic syndrome 1 0.3 100.0

# 1998 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 7: 331±337 (1998)
334 J. P. CONNOLLY ET AL.

Table 2 Ð A comparison of the mean prescribed daily dosages (MPDD) of captopril, enalapril and lisinopril with
the de®ned daily dosages (DDD) for these drugs in patients with congestive heart failure and hypertension
Congestive heart failure Hypertension
(MPDD) (MPDD)
Captopril 50.3 mg/day (1.0 DDD; n ˆ 37) 56.0 mg/day (1.1 DDD; n ˆ 31)
Enalapril 8.8 mg/day (0.4 DDD; n ˆ 4) 15.0 mg/day (0.8 DDD; n ˆ 25)
Lisinopril 9.17 mg/day (0.46 DDD; n ˆ 10) 9.86 mg/day (0.49 DDD; n ˆ 69)
n refers to the number of patients for which a prescribed daily dosage could be calculated.

lisinopril three were prescribed 2.5 mg per day,
four were prescribed 5 mg per day, two were
prescribed 10 mg per day and one was prescribed
40 mg per day.
Of the 353 patients with congestive heart failure
53 (17.7%) were prescribed a hypnotic drug, and
41 (13.1%) had a diagnosis of insomnia recorded
on the same encounter. When patients aged
60 years and over were selected a signi®cantly
higher proportion of patients with heart failure
were prescribed a hypnotic drug compared to
patients without heart failure (14.7% versus
8.3%; p 5 0.001). Similarly, when patients aged
60 years and over were selected a signi®cantly
higher proportion of patients with heart failure had
the co-existence of insomnia compared to patients
without heart failure (11.8% versus 6.9%;
p 5 0.001).
The use of ACE inhibitors in hypertension
All patients with a diagnosis of hypertension were
selected from the database (regardless of what
drugs were prescribed). A total of 1214 patients
had diagnosis of hypertension and a total of 1391
items were prescribed.
Of the 1214 patients with hypertension 179
(14.7%) were prescribed an ACE inhibitor. The
four therapeutic groups most frequently prescribed
in hypertension were beta-adrenoceptor blocking
drugs (29.2% of items), calcium channel blocking
drugs (18.6% of items), thiazide diuretics (15.7%
of items) and ACE inhibitors (12.3% of items,
Table 3).
The mean prescribed daily dosage of captopril in
patients with hypertension was 56.0 mg per day
(1.1 de®ned daily dosages). The mean prescribed

Table 3 Ð Frequencies of di€erent therapeutic groups used in the treatment of hypertension

Therapeutic group Frequency Percentage of groups Cumulative
used in hypertension percentage
Beta-adrenoceptor blocking drugs 424 29.2 29.2
Calcium-channel blocking drugs 269 18.6 47.8
Thiazide diuretics 228 15.7 63.5
Angiotensin converting enzyme inhibitors 179 12.3 75.8
Compound potassium-sparing diuretics 124 8.6 84.4
No prescription given 59 4.1 88.5
Alpha-adrenoceptor blocking drugs 42 2.9 91.4
Centrally acting antihypertensive drugs 32 2.2 93.6
Diuretics with potassium 19 1.3 94.9
Loop diuretics 17 1.2 96.1
Unclassi®ed drugs* 14 1.0 97.0
Nitrates 11 0.8 97.8
Aspirin 10 0.7 98.5
Potassium supplements 6 0.4 98.9
Vasodilator antihypertensives 5 0.3 99.2
Adrenergic neurone blocking drugs 4 0.3 99.5
Anxiolytics 3 0.2 99.7
Analgesics 2 0.1 99.9
Potassium sparing diuretics 2 0.1 100.0
* Unclassi®ed drugs are drugs which cannot be prescribed on the National Health Service.

# 1998 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 7: 331±337 (1998)
 ACE USAGE IN GENERAL PRACTICE
daily dose of enalapril in patients with hyper-
tension was 15.0 mg per day (0.8 de®ned daily
dosages). The mean prescribed daily dosages of
lisinopril in hypertension was 9.9 mg per day (0.5
de®ned daily dosages).
There was no signi®cant di€erence in the mean
prescribed daily dosages between patients with
hypertension and patients with heart failure for
captopril, enalapril or lisinopril.
DISCUSSION
The majority (60.6%) of ACE inhibitors were
prescribed without a consultation. This highlights a
potential drawback of repeated prescribing, in that
there is loss of control by the doctor over the
supervision and management of the patient.16 This
is re¯ected in the ®nding that 62.2% of prescrip-
tions in which ACE inhibitors were co-prescribed
with potassium sparing diuretics, diuretics with
potassium supplements or with NSAIDs were
repeat prescriptions. In all of these cases because
of the risk of drug interactions, it would be
desirable to review the existing medication before
adding the new agent. Were the doctor to review
the medication speci®cally, the option to identify
and avoid such con¯icts may improve the quality of
prescribing.
The majority of ACE inhibitors were used in the
treatment of hypertension and only a minority were
used in the treatment of congestive heart failure. A
small minority of ACE inhibitors were prescribed
for unlicenced indications. Evidence from North-
ern Ireland's prescribing database has shown that
prescribing of ACE inhibitors increased by 126%
between 1988 and 1991.17 Therefore, this increase
was almost certainly due to increased prescribing
for hypertension, to the extent that ACE inhibitors
became the fourth most frequently prescribed
therapeutic group to patients with hypertension
in 1994. It is not known from the database what
proportion of hypertensive patients were com-
menced on an ACE inhibitor because thiazide
diuretics and beta-adrenoceptor antagonists were
contraindicated or were not tolerated.
Only 18.1% of patients with congestive heart
failure were prescribed ACE inhibitors, despite the
known clinical bene®ts and cost-e€ectiveness of
these drugs. Those patients with congestive heart
failure who were prescribed ACE inhibitors tended
to be prescribed dosages which were considerably
below their de®ned daily dose and which were
# 1998 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 7: 331±337 (1998)
335
below the daily dosages used in clinical trials (up to
150 mg captopril4and 20±40 mg of enalapril1±3).
Caution in the use of ACE inhibitors in heart
failure and their use at low dosage, may re¯ect
prescribing caution due to the known hazards such
as ®rst dose hypertension, and also uncertainty or
lack of con®dence on the underlying diagnosis of
congestive heart failure. There is no evidence that
lower doses of ACE inhibitors may be more
appropriate to patients in general practice.
A signi®cantly higher proportion of elderly
patients with congestive heart failure were pre-
scribed hypnotics, and had the co-existence of
insomnia compared to elderly patients who did not
have congestive heart failure. This could be a
re¯ection of suboptimal control of the heart failure
and to that extent the prescription of such
hypnotics may not be particularly helpful, when
the goal should be to optimize the residual cardiac
pumping function, rather than to prescribe symp-
tomatically.
Due to the short duration of the study the
proportion of patients with congestive heart failure
who were prescribed ACE inhibitors could be an
underestimate. It is possible that some of the study
patients with congestive heart failure were taking
ACE inhibitors, but were missed, because they were
not prescribed these drugs during the study period.
Similarly, the proportion of patients with conges-
tive heart failure who were prescribed hypnotics or
had the co-existence of insomnia is also likely to be
an underestimate of the true value. Until it is
possible to quantify the co-prescribing of drugs on
large computerized databases the degree of inac-
curacy will not be known. Also, it is not known
what proportion of patients had contraindications
to ACE inhibitors.
This study has not yet been repeated, therefore it
is not possible to determine how prescribing for
heart failure or hypertension has changed over
time.
Congestive heart failure is a common and serious
public health problem.18,19 The prevalence of
congestive heart failure is 0.4±2% in the United
Kingdom, and about 10% in the elderly popula-
tion.19 There is also evidence that the incidence of
congestive heart failure is rising in the United
Kingdom.20 When compared with other common
chronic medical conditions congestive heart failure
was shown to have the greatest impact on physical
functioning, social activity, perceived well-being
and the ability to carry out everyday tasks.21
Therefore, public health policy should be to
336 J. P. CONNOLLY ET AL.
encourage appropriate use of ACE inhibitors in
patients with congestive heart failure.22
CONCLUSIONS
This study suggested misdirected use of ACE
inhibitors in primary care. There was under-use
of these drugs in the treatment of congestive heart
failure and the daily dosages prescribed were less
than those suggested as bene®cial in clinical
studies. The high frequency of inter-current drug
usage, with potential adverse interactions, would
suggest a more careful surveillance policy for such
patients. Appropriate health targets and protocols
for congestive heart failure to facilitate the early
diagnosis of reduced left ventricular function, and
prompt therapy with ACE inhibitors are suggested.
Better management of the process of repeat
prescribing by general practitioners would be
helpful in this regard.
ACKNOWLEDGEMENTS
Funding was provided from the budget of the Drug
Utilization Research Unit, Department of Thera-
peutics and Pharmacology, the Queen's University
of Belfast.
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# 1998 John Wiley & Sons, Ltd. Pharmacoepidemiology and Drug Safety, 7: 331±337 (1998)