Rational pharmacotherapy of hypertension in the elderly: analysis of the choice and dosage of drugs

Rational pharmacotherapy of hypertension in the elderly:analysis of the choice and dosage of drugs

K. A. Jassim Al Khaja PhD, R. P. Sequeira PhD and V. S. Mathur MD DPhil (Oxon)

Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian GulfUniversity, Bahrain

SUMMARY

Objectives: To determine in older people with

uncomplicated hypertension: (a) the pattern of

prescribing of antihypertensives; (b) the extent of

physicians' adherence to recommendations on

dosage for antihypertensive combinations; (c)

whether prescribing practice conforms with

recommended therapeutic guidelines; and (d) the

frequency of prescribing of other drugs which

have the potential to alter the ef®cacy of antihy-

pertensive agents.

Methods: A survey of prescribing in older

patients with uncomplicated hypertension in

primary care setting of Bahrain was conducted.

Results: Of the 432 (56á5%) patients on mono-

therapy, 192 (44á4%) were treated with b-blockers,

87 (20á1%) with calcium channel blockers (CCBs),

53 (12á3%) with a-methyldopa, 47 (10á9%) with

diuretics, 46 (10á6%) with angiotensin converting

enzyme (ACE) inhibitors, and 7 (1á6%) with

hydralazine. Of the 1146 patients on mono- or

combination therapies, 434 (56á8%) were treated

with b-blockers, 244 (31á9%) with diuretics, 211

(27á6%) with CCBs, 139 (18á2%) with ACE inhib-

itors, 103 (13á5%) with a-methyldopa 8 (1á0%)

with brinerdine and 7 (0á9%) with hydralazine. In

the 332 (43á5%) patients on combination therapy,

15 different two- and three-antihypertensive drug

combinations were prescribed: a diuretic with a

b-blocker (37á2%) and a b-blocker with either a

CCB (20á9%) or an ACE inhibitor (12á4%) were the

most popular two-drug regimens. The most com-

monly prescribed triple drug regimens were a

diuretic and a b-blocker plus either a CCB (26á1%)

or an ACE inhibitor (17á4%) and diuretic plus an

ACE inhibitor and a CCB (15á2%). Daily dosage of

b-blockers, ACE inhibitors and a-methyldopa

were somewhat high in a considerable proportion

of patients on both mono- and combined therap-

ies. A substantial proportion (9á7%) of patients on

monotherapy were treated with immediate

release nifedipine.

Conclusion: The pharmacotherapy of hyperten-

sion in elderly patients was found in some

instances not to conform to recommended

guidelines. For certain classes of antihypertensive

agent such as b-blockers, ACE inhibitors and

a-methyldopa, neither the principles of geriatric

pharmacology nor of antihypertensive combina-

tion therapy, and in particular, the need to reduce

daily dosage, were followed. The use of imme-

diate release nifedipine in the elderly is irra-

tional, and instead, the use of long-acting

dihydropyridine CCBs should be considered. The

results of long-term randomized clinical trials

published during the last decade have had a

minimal impact on clinical practice of primary

care physicians in Bahrain.

Keywords: antihypertensive drugs, elderly hyper-

tensives, prescribing patterns1

INTRODUCTION

In the elderly, hypertension is the most important

modi®able and treatable risk factor for cerebro-

vascular disease, congestive heart failure, coronary

artery disease and end-stage renal failure (1), and

its prevalence, particularly isolated systolic hyper-

tension (ISH), is considerable in this age group

(2, 3). Systolic blood pressure appears to be more

strongly related to, and is a better predictor of,

cardiovascular complications than diastolic blood

pressure (2). Trials in elderly hypertensive patients

Received 18 October 2000, accepted 8 November 2000.

Correspondence: Dr K. A. Jassim Al Khaja, Department of

Pharmacology and Therapeutics, College of Medicine and

Medical Sciences, Arabian Gulf University, PO Box no. 22979,

Bahrain. Tel.: + 973 239773; fax: + 973 271090; e-mail: khlidj@

agu.edu.bh

Journal of Clinical Pharmacy and Therapeutics (2001) 26, 33±42

Ó 2001 Blackwell Science Ltd 33

have documented that antihypertensive therapy

of diastolic (4±7) and isolated systolic (4, 8±10)

hypertension reduces the risk of cardiovascular

complications. Lowering blood pressure to the

desired level in the elderly has greater absolute

bene®ts in terms of preventing stroke or coronary

events compared with younger patients (11, 12)

because such complications are more frequent in

the elderly (11). Moreover, lowering blood pressure

in older people with ISH has been reported to

reduce the incidence of heart failure (10), dementia

(13) and the clinical bene®ts of antihypertensive

therapy are now widely accepted (14±16).

However, antihypertensive therapy in the elderly

should be used with care choosing appropriate

drugs. The choice of antihypertensive agent(s)

seems to be guided by several considerations.

Firstly, unless contraindicated, those antihyperten-

sives documented to reduce cardiovascular mor-

bidity and mortality are the agents of choice.

Secondly, antihypertensives should be prescribed in

their minimum effective dose because of the poten-

tial for either increased bioavailability or delayed

elimination rate of some of these drugs, which can

occur in the elderly as a result of declining hepatic

and renal function. A prudent therapeutic strategy is

required to avoid the adverse effects, which can

impair quality of life, and also to enhance compli-

ance (17). Other factors related to ageing, such as

physiological and pathological changes, comorbid-

ities and functional and cognitive impairment

should also be considered. Polypharmacy should be

avoided as much as possible because the risks of

drug±disease interactions and drug±drug interac-

tions are increased in the elderly population.

We therefore decided to conduct a survey of

prescribing to:

(i) Determine the pattern of prescribing of anti-

hypertensive agents (i.e. either as monother-

apy or combination therapy) by primary care

physicians and overall drug prescribing in

elderly patients with uncomplicated hyper-

tension.

(ii) Analyse whether physicians followed recom-

mendations to use reduced doses of antihy-

pertensives, including combination prepara-

tions, in older people.

(iii) Identify whether physicians' prescribing

practice conformed with recommended

therapeutic guidelines.

(iv) Analyse the use of other drugs prescribed

concomitantly in elderly patients with hyper-

tension which have the potential to alter the

ef®cacy of antihypertensives or causing

adverse reactions.

METHODS

Setting

Antihypertensive prescribing pattern was evaluated

in elderly individuals aged 65 years or above in

seven out of total 18 health centres. The number of

patients registered was 229 300, representing 46%

of the of®cially registered individuals of these 18

health centres and 35á7% of the population of

Bahrain (2 18). From the selected health centres,

we therefore expected to identify the prescribing

patterns of 35 (43%) primary care physicians in

Bahrain.

Study population

Relevant data were collected using cards known as

chronic dispensing cards, specially designed for

chronically ill patients. The purpose of these cards

was to monitor the drug re®lling process and to

provide a brief dispensing record for each health

centre's pharmacy. Each dispensing card contained

the patients' personal identi®ers and a list of all

prescribed drugs, including date of dispensing,

number of items and quantity dispensed at each

re®ll. The extreme left two digits of the population

registration card (PRC) number, which indicate the

year of birth, were used to identify patients born

during or prior to 1934, and who were therefore

aged 65 years or above.

Variability

Those cards that included cardiovascular drugs,

such as antihypertensives, antiarrhythmics, antian-

ginal drugs, cardiac glycosides and antithrombotic

drugs, were collected. Classes of antihypertensives

were categorized according to the guidelines of the

subcommittee of the World Health Organization/

International Society of Hypertension (15) as fol-

lows: diuretics, b-blockers, ACE inhibitors, calcium

channel blockers (CCBs), angiotensin II receptor

antagonists, a-adrenoceptor blocking drugs, and

Ó 2001 Blackwell Science Ltd, Journal of Clinical Pharmacy and Therapeutics, 26, 33±42

34 K. A. Jassim Al Khaja et al.

other drugs, including centrally acting sympatho-

lytic a-methyldopa and directly acting vasodilators.

Data collection was carried out between 3

November 1998 and 30 January 1999. Patients aged

65 years or above with uncomplicated essential

hypertension were included in this study. For the

purpose of present study, we de®ned a patient to

be hypertensive if he or she received one or more

antihypertensive drugs and was apparently free of

cardiovascular diseases other than hypertension.

However, elderly patients with hypertension

were excluded from the study if they also had:

ischaemic heart disease as indicated by prescribed

antianginal agents with antihypertensives and

antiplatelet/antithrombotic drugs; diabetes mell-

itus; cardiac glycosides in combination with other

cardiovascular drugs, possibly for congestive heart

failure and/or dysrhythmias; migraine and were

receiving prophylactic low-dose propranolol; a

thyroid condition and were receiving adjuvant low

dose adjuvant propranolol; anaemia and were on

oral iron therapy and b-blockers; or secondary

hypertension.

It should be pointed out that administration of

antihypertensives, particularly those given in

combination therapy, may not only be indicated for

controlling hypertension resistant to monotherapy

but also for treating coexisting cardiovascular dis-

eases with or without hypertension. The coexist-

ence of cardiovascular disease dictates which

antihypertensives are prescribed, particularly those

given as combinations, as illustrated by the coad-

ministration of b-blockers, CCBs and antithrom-

botic/antiplatelet drugs for patients with ischaemic

heart disease, diuretics plus ACE inhibitors for

patients with heart failure, and b-blockers plus

non-dihydropyridine CCBs for patients with dys-

rhythmias. In order to avoid the in¯uence of com-

orbidity in prescribing and to further validate our

study, medical records of those patients receiving

any of the abovementioned antihypertensive com-

bination regimens were carefully retrieved and

those who ful®lled our exclusion criteria were

eliminated. The detailed methodology has been

described previously (19).

RESULTS

The demographic and medical characteristics of the

study population (764 elderly hypertensive

patients) are presented in Table 1. Mean age (� SD)

was 71á8 � 6á08 (range 65±95, median 70) years. A

total of 432 (56á5%) patients were on monotherapy,

whereas 332 patients (43á5%) were on combination

antihypertensive therapy. The mean number (� SD)

of antihypertensive(s) per prescription was 1á5 �

0á63 and the mean number of all drugs used

(antihypertensives and other drugs) was 2á12 � 1á03

per prescription.

Table 2 presents a summary of the pattern of

prescribing of antihypertensive drugs as mono-

therapy and as both mono- and combined therapies

(i.e. total use) in elderly patients with uncompli-

cated hypertension. In the monotherapy category,

the classes of drugs used were as follows: b-block-

ers 44á4% (atenolol 43á7% and propranolol 0á7%),

CCBs 20á1% (immediate and sustained release nif-

edipine 9á7% and 9á9%, respectively, immediate

release verapamil 0á2% and amlodipine 0á2%),

Table 1. Demographic characteristics of 764 elderly

hypertensive patients and proportion of those who

undergo monotherapy and combination therapy

Items Frequency %

Gender

Male 340 44á5Female 424 55á5

Age group

65±74 567 74á275±84 154 20á2Above 85 43 5á6

Age (years)

Mean 71á8 � 6á08*

Median 70

Range 65±95

Antihypertensive therapy

Monotherapy 432 56á5Two-drug Combination 282 36á9Three-drug Combination 46 6á0Four-drug Combination 4 0á5Number of Antihypertensive (s) 1á51 � 0á63*

per prescription

Range (drugs) 1±4

Number of overall drugs 2á12 � 1á03*

per prescription+

Range (drugs) 1±6

* Mean � SD.+ Indicates antihypertensive(s) + other drug(s).


Antihypertensives in the elderly 35

a-methyldopa 12á3%, diuretics 10á9% (indapamide

4á6%, hydrochlorothiazide (HCTZ) 3á25%, HCTZ

plus triamterene `dyazide' 2á1% and chlorthalidone

0á93%), ACE inhibitors 10á6% (enalapril 4á6%,

captopril 3á7%, lisinopril 1á4%, and perindopril

0á9%) and brinerdine 1á6%. Looking at total use of

antihypertensives (i.e. both mono- and combined

therapy), b-blockers were again the most often

prescribed class 56á8% (atenolol 55%, propranolol

1á7% and metoprolol 0á1%). Diuretics ranked sec-

ond 31á9% (dyazide 10á7%, HCTZ 9á9%, indapa-

mide 8á2%, chlorthalidone 2% and furosemide

1á2%), followed by CCBs 27á6% (immediate and

sustained release nifedipine 11á6% and 15á2%,

respectively, immediate release diltiazem and

verapamil 0á13% and 0á39%, respectively, and

amlodipine 0á26%), ACE inhibitors 18á2% (captop-

ril 9á0%, enalapril 4á3%, lisinopril 3á5%, perindopril

1á2% and benazepril 0á13%), a-methyldopa 13á5%,

brinerdine 1% and hydralazine 0á9%.

Fifteen different two-drug antihypertensive

combinations were prescribed to elderly patients

with hypertension (Table 3). Their rank order was

as follows: a diuretic with a b-blocker (37á2%) and a

b-blocker with either a CCB (20á9%) or an ACE

inhibitor (12á4%). Fifteen different triple drug

combinations were used (Table 3), and the most

frequently prescribed combinations were a diuretic

and a b-blocker plus either a CCB (26á1%) or an

ACE inhibitor (17á4%), and a diuretic and an ACE

inhibitor plus a CCB (15á2%).

Analysis of the dosage in both the monotherapy

and combination regimens is shown in Figs 1±4.

Figure 1 shows the proportion of b-blockers given

at low, moderate and high doses on the two-drug

regimens as 2á5%, 40á4% and 57á1%, respectively,

whereas the corresponding values for the three-

Therapy

Antihypertensive drugs

Monotherapy

frequency (%)

Overall utilization*

frequency (%)

b-Blockers 192 (44á4) 434 (56á8)

Diuretics 47 (10á9) 244 (31á9)

ACE inhibitors 46 (10á6) 139 (18á2)

Calcium channel blockers 87 (20á1) 211 (27á6)

Methyldopa 53 (12á3) 103 (13á5)

Hydralazine ± 7 (0á9)

Brinerdine 7 (1á6) 8 (1á0)

Total 432 (100) 1146 (149á8)**

* Indicates monotherapy + combination therapy.

** Total exceeds 100% since the average patient received more than one drug.

Table 2. Antihypertensives:

monotherapy and overall utilization

in elderly hypertensive patients

Table 3. Antihypertensive combination therapy in

elderly hypertensive patients

Two-drug

regimen

Total

n (%)

Three-drug

regimen

Total

n (%)

B + D 105 (37á2) D + B + C 12 (26á1)

B + C 59 (20á9) D + B + A 8 (17á4)

B + A 35 (12á4) D + A + C 7 (15á2)

D + MD 19 (6á7) B + A + C 4 (8á7)

D + A 18 (6á4) D + B + MD 3 (6á5)

D + C 13 (4á6) D + A + MD 2 (4á3)

C + A 11 (3á9) D + C + MD 2 (4á3)

MD + B 8 (2á8) B + C + MD 1 (2á2)

MD + C 8 (2á8) B + A + MD 1 (2á2)

MD + A 1 (0á4) A + C + MD 1 (2á2)

MD + H 1 (0á4) D + B + H 1 (2á2)

MD + Br 1 (0á4) B + A + H 1 (2á2)

Br + H 1 (0á4) D + MD + H 1 (2á2)

D + D 1 (0á4) D + C + H 1 (2á2)

A + A 1 (0á4) A + C + C 1 (2á2)

Total 282 (100) Total 46 (100)

D = Diuretics; B = b-blockers; C = Calcium channel blockers;

A = Angiotensin converting enzyme inhibitors;

MD = Methyldopa; H = Hydralazine; Br = Brinerdine.



drug regimens were 0á0%, 17á2% and 82á8%.

Approximately 32% of b-blockers prescribed in a

high dose were in the monotherapy category.

The proportion of ACE inhibitors given at low,

moderate and high doses (Fig. 2) as monotherapy

was 28á3%, 54á3% and 17á4%, respectively. How-

ever, the corresponding percentages were 32á8%,

44á8% and 22á4% for two-drug regimens, and 20%,

48% and 32% for three-drug regimens. With

respect to diuretics, the thiazide diuretics, partic-

ularly those prescribed in a daily dose of 25 mg

HCTZ or equivalent, were the most commonly

used drugs (Fig. 3). However, their use at high

dose (50 mg HCTZ or equivalent) was 14á9% in the

monotherapy category and 9á9% and 11á8% in the

two- and three-drug regimens, respectively. How-

ever, the use of thiazides at a a low daily dose

(12á5 mg HCTZ or equivalent), was rare.

If patients were on a-methyldopa, low to mod-

erate doses (Fig. 4) were commonly used. How-

ever, a considerable proportion of high doses were

also used as both mono- and combined therapy.

Among CCBs, the dihydropyridine derivative

nifedipine was the most commonly prescribed.

Immediate and sustained release nifedipine for-

mulations were prescribed at acceptable minimal

dosage ranges of 10±30 and 20±40 mg daily in

divided doses, respectively, in both mono- and

combined therapies.

DISCUSSION

The value of treating hypertension in elderly

patients who have either combined systolic and

diastolic hypertension or isolated systolic hyper-

tension has been demonstrated in long-term ran-

domized clinical trials (4±6, 9, 20). These trials have

documented a reduction in fatal and nonfatal

strokes and coronary heart disease. With the

exception of the HEP study (20), all the trials

Fig. 1. Daily dosage of atenolol prescribed to elderly

hypertensive patients on monotherapy and combination

regimens.

Fig. 2. Daily dosage of ACE inhibitors prescribed to

elderly hypertensive patients on monotherapy and

combination regimens. Low dose/day indicates captopril

6á25±25 mg; enalapril 5 mg; lisinopril 2á5±5 mg; perin-

dopril 2 mg; benazepril 10 mg. Moderate dose/day

indicates captopril 37á5±75 mg; enalapril 10±15 mg; lis-

inopril 10±15 mg; perindopril 4 mg. High dose/day

indicates captopril ³100 mg; enalapril ³20 mg; lisinopril

³20 mg; perindopril 8 mg.



(4±6, 9) used thiazide diuretics in relatively low

doses as ®rst-line agents. This ®nding was the basis

for recommendations from the National High

Blood Pressure Education Program Working

Group on Hypertension in the Elderly (2), and the

current therapeutic guidelines (14±16) consider low

dose thiazide diuretics as the most appropriate

®rst-line agents for treatment of uncomplicated

hypertension in the elderly, unless there are par-

ticular reasons for using other agents. However, we

found a remarkable underutilization of diuretics as

monotherapy (Table 2). The rate of overall diuretic

use was also relatively low and ranked second

when compared to b-blockers, the most commonly

prescribed antihypertensive agent in the elderly in

our study. This ®nding is remarkably different

from that of US studies (21, 22), but comparable to

that in Sweden (23). Concern about diuretic-in-

duced hypokalaemia and the subsequent increased

rate of sudden cardiac death found in the Multiple

Risk Factor Intervention Trial (MRFIT), which was

widely publicized (24), might account for the

underprescribing of diuretics. Interestingly, such

claims have now been refuted, by the results of the

MRC (4) and SHEP (9) trials.

b-blockers were extensively prescribed by phy-

sicians in our study, despite the acknowledged

superiority of thiazides over b-blockers in terms of

reduction and prevention of cardiovascular com-

plications (11±16). Moreover, the b-blocker arm of

the MRC trial, which incorporated atenolol as a

®rst-line agent, failed to show any effect on cardiac

events and fatal and nonfatal strokes. Recently, a

meta-analysis of 10 selected randomized trials in

the elderly came to a similar conclusion (25). The

use of b-blockers as monotherapy in the elderly is

not recommended unless comorbidity such as

coronary artery disease and postmyocardial

infarction is also present (2, 14±16). We therefore

believe that the prescribing of b-blockers at a rate of

44á4% as monotherapy and 56á8% overall appears

Fig. 3. Daily dosage of thazide and thiazide-like diuret-

ics prescribed to elderly hypertensive patients on

monotherapy and combination regimens. Low dose/day

indicates 12á5 mg hydrochlorothiazide (HCTZ) or

equivalent. Moderate dose/day indicates 25 mg HCTZ,

25 mg chlorthalidone, 2á5 mg indapamide and a daily

tablet of dyazide that included 25 mg HCTZ and 50 mg

triamterene. High dose/day indicates 50 mg HCTZ or

50 mg chlorothalidione or equivalent.

Fig. 4. Daily dosage of a-methyldopa prescribed to

elderly hypertensive patients on monotherapy and

combination regimens.



to be high for a study population which included

elderly individuals with uncomplicated hyperten-

sion. This prescribing pattern, of course, does not

conform to the current therapeutic guidelines.

Recent evidence has shown that the moderately

long-acting dihydropyridine CCB nitrendipine

reduces the risk of stroke and major cardiovascular

events in patients aged 60 years or older with ISH

(8). Moreover, long-acting dihydropyridine CCBs

are recommended as suitable alternatives for ISH

in the elderly when thiazides are ineffective, con-

traindicated or not tolerated (14±16). Based on our

prescription analysis, CCBs were the second most

frequently prescribed agents in the monotherapy

category (Table 2). The dihydropyridine derivative

nifedipine accounted for 98% of prescribed CCBs,

and approximately half the prescribed nifedipine

(49á4%) was an immediate release formulation.

Recently, concern has been expressed about the

safety of short-acting CCBs in treating hyperten-

sion because their use appears to be associated

with an increased risk of cardiovascular events and

death (26±28). However, the safety of long-acting

dihydropyridine CCBs in elderly patients has been

documented by the recent Prospective Random-

ized Amlodipine Survival Evaluation (PRAISE)

and Systolic Hypertension in Europe (Syst-Eur)

trials (29, 30). Although approximately half of the

nifedipine was prescribed as sustained release

formulations, the long-acting amlodipine or the

other dihydropyridine derivatives available in

Bahrain, were rarely used. Therefore a policy

decision needs to be taken by the authorities

restricting the use of short-acting nifedipine

monotherapy and encouraging the use of CCBs

with slow onset and prolonged duration of action.

The use of combination therapy is widely

accepted as an approach to optimize blood pres-

sure, both to minimize adverse effects and to obtain

synergistic effects by using two or more comple-

mentary antihypertensives with different modes of

action in submaximal dosage (14±16). Prescribing

of antihypertensives in their lowest effective doses

in elderly patients can help to avoid adverse drug

reactions and improve quality of life. This is

because elderly patients, even those with normal

liver and kidney function, have a reduced rate of

drug metabolism and elimination compared with

younger people (17).

In clinical practice, a low-dose diuretic/b-blocker

combination has been associated with enhanced

antihypertensive ef®cacy and a reduction in car-

diovascular morbidity and mortality (4, 5, 9). In our

study, this combination was found to be the most

frequently prescribed dual-drug regimen. How-

ever, the prescribing frequency of the hydrophilic

b1-selective atenolol given at high dose (100 mg

once daily) in combination regimens was high. This

does not conform with the guidelines for use of

antihypertensive combination therapy, and it may

also increase the severity of adverse effects as a

result of declining cardioselectivity and reduced

renal function in the elderly (31). In the SHEP trial

(9), the use of very low dose of chlorthalidone

(12á5 mg), with low-dose atenolol (25±50 mg)

added as required, resulted in a signi®cant reduc-

tion in cardiovascular events. We found that the

current recommendations to prescribe low dose

thiazide diuretics (12á5 mg HCTZ or equivalent) as

®rst-line agents were rarely followed (mono- and

combination together; 0á9%), whereas a high dose

(50 mg HCTZ or equivalent) was frequently used

(11á2%; Fig. 3). This prescribing pattern is unfor-

tunate because adverse effects are least likely to be

encountered with low doses.

High doses of ACE inhibitors (as de®ned in

Fig. 2) in combination therapy were commonly

prescribed. However, dosage reductions are

necessary to avoid the bothersome dry cough,

which is especially common in older individuals

(32). Dosage of hydrophilic ACE inhibitors with a

long duration of action must also be reduced in

patients with impaired renal function (33).

The prescribing of a-methyldopa as monothera-

py was higher than that of other more important

antihypertensives such as diuretics and ACE

inhibitors (Table 2). Moreover, approximately

27±54á5% (average 40%) of patients on a-meth-

yldopa-based combination therapy received a high

dose of this medication (Fig. 4). In elderly patients,

the adverse effects of a-methyldopa, including

sedation, depression and orthostatic hypotension

are particularly unwelcome.

A trend towards utilization of irrational two-

drug combinations (e.g. a b-blocker with an ACE

inhibitor) over rational ones (e.g. a CCB with an

ACE inhibitor or a diuretic with an ACE inhibitor)

was observed (Table 3). The use of a diuretic with

an ACE inhibitor combination in low doses, has



been shown to be effective in lowering blood pres-

sure in the elderly (34, 35) and has similar ef®cacy to

conventional antihypertensive therapy (diuretics,

b-blockers or both) in prevention of cardiovascular

mortality and major morbidity (36). Nonetheless,

this rational combination was one of the less com-

monly prescribed regimens and accounted for just

6á4% of prescribed two-drug regimens. It should be

emphasized that the risk of diuretic-induced hypo-

kalaemia is signi®cantly attenuated by concurrent

use of an ACE inhibitor (37).

Non-steroidal anti-in¯ammatory drugs (NSA-

IDs), antacids and H2-receptor blockers are widely

prescribed in older people. NSAIDs are often given

on a regular basis for chronic musculo-skeletal

disorders, whereas antacids and H2-receptor

blockers are administered to reduce NSAIDs-asso-

ciated gastrointestinal symptoms. The long-term

use of NSAIDs in the elderly is associated with

pharmacodynamic interactions resulting in an ele-

vation in blood pressure, an effect more marked in

patients who concurrently receive antihyperten-

sives (38). Piroxicam and indomethacin have a

greater tendency to blunt the ef®cacy of antihy-

pertensives (38, 39), whereas diuretics, b-blockers

and ACE inhibitors are the classes of antihyper-

tensives most prone to demonstrate this interaction

with NSAIDs (39). We found that approximately

one quarter of our study population (27á4%) were

on NSAIDs, including diclofenac (13á7%), low-dose

acetylsalicylic acid (8á2%), indomethacin (4á2%)

and ibuprofen (1á3%). Prescribing NSAIDs in their

lowest effective doses and using those with a

minimal hypertensive effect is necessary to limit

the negative impact on antihypertensive ef®cacy.

CCBs, which are probably not affected by NSAIDs,

could be the preferred antihypertensives in elderly

patients who need NSAIDs on a regular basis (39).

Antacids have been found to reduce the bio-

availability of ACE inhibitors by pharmacokinetic

interaction (40) and to attenuate the antihyperten-

sive ef®cacy of these drugs (16). In our study, 5á8%of patients were on antacids, and with respect to

H2-receptor blockers, 2á6% of patients were on

cimetidine and 6á2% were on ranitidine. Cimeti-

dine, the cytochrome P450 inhibitor, has been

reported to increase the bioavailability of CCBs and

lipophilic b-blockers (40) and may increase their

antihypertensive effect (16).

CONCLUSION

Prescribing of antihypertensive agents in older

people by primary care physicians did not always

conform to current guidelines. This was clearly

illustrated by under-utilization of thiazide diuretics

as ®rst-line agents and over-prescription of

b-blockers. The prescribed doses of some antihy-

pertensive agents such as b-blockers, ACE inhibi-

tors and central-acting a-methyldopa were

considerably higher than the usual recommended

dose. Despite concern about the possible detri-

mental effects of immediate release CCBs as

monotherapy in elderly hypertensives, these were

inappropriately prescribed in a considerable pro-

portion of patients. Moreover, to avoid blunting of

antihypertensive ef®cacy, drugs such as NSAIDs,

which are commonly used in elderly people,

should be carefully selected. Finally, it is reassuring

that in primary health care, elderly individuals

with uncomplicated hypertension were subjected

to limited polypharmacy.

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Rational pharmacotherapy of hypertension in the elderly: analysis of the choice and dosage of drugs