阿司匹林和ACEI相互作用

今天读了

Stockley's Drug Interactions 8th Edition

，其中阿司匹林与

ACEI

家参考：

The antihypertensive efficacy of captopril

and enalapril may

be reduced

by high-dose aspirin in about

50% of patients. Low- dose aspirin (less than or equal to 100 mg daily) appears to have little effect.

It

is

unclear

whether

aspirin

attenuates

the

benefits

of

ACE

inhibitors

in

heart

failure.

The

likelihood

of an interaction may depend on disease state and its severity.

Renal failure has been reported in a patient taking captopril and aspirin.

Clinical evidence

A. Effects on blood pressure

(a) Captopril

Aspirin 600 mg every 6 hours for 5 doses did not significantly alter the blood pressure response to

a single 25 to 100-mg dose of captopril in 8 patients with essential hypertension. However, the

staglandin response to captopril was blocked in 4 of the 8, and in these patients, the blood pressure

response to captopril was blunted.1 In another study, aspirin 75 mg daily did not alter the

antihypertensive effects of captopril 25 mg twice daily in 15 patients with hypertension.

(b) Enalapril

Two groups of 26 patients, one with mild to moderate hypertension taking enalapril 20 mg twice daily

and the other with severe primary hypertension taking enalapril 20 mg twice daily (with nifedipine

30 mg and atenolol 50 mg daily), were given test doses of aspirin 100 and 300 mg daily for 5 days.

The 100-mg dose of aspirin did not alter the efficacy of the antihypertensive drugs, but the 300-mg

dose

reduced

the

antihypertensive

efficacy

in

about

half

the

patients

in

both

groups.

In

these

patients,

the antihypertensive effects were diminished by 63% in those with mild to moderate hypertension and

by 91% in those with severe hypertension. In contrast, another study in 7 patients with hypertension

taking enalapril

(mean

daily

dose

12.9

mg)

found

that

aspirin

81

mg

or

325

mg

daily

for

2

weeks

did

not

have

any

significant

effect on blood pressure.4 A further study in 18 patients also found that aspirin 100 mg daily for

2 weeks did not alter the antihypertensive effect of enalapril 20 or 40 mg daily.

(c) Unspecified ACE inhibitors

In

a

randomised

study,

the

use

of

low-dose

aspirin

100

mg

daily

for

3

months

did

not

alter

blood

pressure

control in patients taking calciumchannel

blockers or ACE inhibitors, when compared with placebo.

Similarly,

in a re-analysis of data from the Hypertension Optimal Treatment

(HOT) study, long-term

low- dose aspirin 75 mg daily did not interfere with the blood pressure-lowering effects of the

antihypertensive drugs studied, when compared with placebo. Of 18 790 treated hypertensive patients,

about 82% received a calcium-channel blocker, usually felodipine alone or in combination, and 41%

received an ACE inhibitor, usually in combination with felodipine.

B. Effects in coronary artery disease and heart failure

Various pharmacological studies have looked at the short-term effects of the combination of ACE

inhibitors

and

aspirin

on

haemodynamic

parameters.

In

one

study

in

40

patients

with

decompensated

heart

failure, aspirin 300 mg given on the first day and 100 mg daily thereafter antagonised the short-term

haemodynamic

effects

of

captopril

50

mg

given

every

8

hours

for

4

days.

The

captopril-induced

increase

in

cardiac

index

and

the

reduction

in

peripheral

vascular

resistance

and

pulmonary

wedge

pressure

were

all abolished.8 In another study, in 15 patients with chronic heart failure receiving treatment with

ACE inhibitors (mainly enalapril 10 mg twice daily), aspirin in doses as low as 75 mg impaired

vasodilatation induced by arachidonic acid.9 In yet another study, aspirin 325 mg daily worsened

pulmonary

diffusion capacity

and

made

the

ventilatory

response to exercise less effective in

patients

taking enalapril 10 mg twice daily, but did not exert this effect in the absence of ACE inhibitors.10

However,

results

from

studies are inconsistent. In a review,11 five

of 7 studies reported aspirin did

not alter the haemodynamic effects of ACE inhibitors whereas the remaining two did. In one of these

studies showing an adverse interaction between aspirin and enalapril, ticlopidine did not interact

with enalapril.

A number of large clinical studies of ACE inhibitors, mostly post-myocardial infarction, have been

re-examined to see if there was a difference in outcome between those receiving aspirin at baseline,

and

those

not.

The

results

are

summarised

in

‘Table

2.2’,

(p.15).

However,

in

addition

to

the

problems

of

retrospective

analysis

of

non-randomised

parameters,

the

studies

vary

in

the

initiation

and

duration

of aspirin and ACE inhibitor treatment and the length of follow-up, the degree of heart failure or

ischaemia, the prognosis of the patients, and the final end point (whether compared with placebo or

with the benefits of aspirin or ACE inhibitors). The conclusions are therefore conflicting, and,

although

two

meta-analyses

of

these

studies

found

no

interaction,

an

editorial13

disputes

the

findings

of one of these analyses.14 In addition to these sub- group analyses, there have been a number of

retrospective

cohort

studies.

A

retrospective

study

involving

576

patients

with

heart

failure

requiring

hospitalisation, showed a trend towards an increased incidence of early readmissions (within 30 days

after discharge) for heart failure among subjects treated with ACE inhibitors and aspirin, compared

with those

treated

with ACE inhibitors without aspirin

(16% versus 10%). In patients without coronary

artery

disease

the

increase

in

readmissions

was

statistically

significant

(23%

versus

10%).15

However,

long-term survival in heart failure was not affected by the use of aspirin with ACE inhibitors.

Furthermore, among patients with coronary artery disease there was a trend towards improvement in

mortality in patients treated with the combination, compared with ACE inhibitor without aspirin (40%

versus 56%).16 Similarly, a lack of adverse interaction was found in a retrospective study involving

14 129 elderly patients who survived a hospitalisation for acute myocardial infarction. However, the

added benefit of the combination over patients who received either aspirin or ACE inhibitors alone

was not statistically significant.

Similarly, in another cohort of patients discharged after first hospitalisation for heart failure,