阿司匹林和ACEI相互作用

1、今天讀了 stocklcy，s drug interactions 8th edition,其中阿司匹林與acei的相互作用有詳細(xì)的說(shuō)明,供大家參考：the anlihypertensive efficacy of captopri 1 and enalapri 1 may be reduced by high-dose aspirin in about50% of patier)ts. low-dose aspirin (less than or equal to 100 mg daily) appears to have little effectit is unclear whether

2、 aspirin attenuates the benefits of ace inhibitors in heart failure the likelihoodof an interaction may depend on disease state and its severity.renal failure has been reported in a patient taking captopril and aspirinclinical evidcncca. effects on blood pressure(a) captoprilaspirin 600 mg every 6 h

3、ours for 5 doses did not significantly alter the blood pressure response toa single 25 to 100-mg dose of captopril in 8 patients with essential hypertension however, thestagland in response to captopri 1 was blocked in 4 of the 8, and in these patie nts, the blood pressureresponse to captopril was b

4、lunted.1 in another study, aspirin 75 mg daily did not alter theantihypertensive effects of captopril 25 mg twice daily in 15 patients with hypertension(b) enalapri1two groups of 26 patients, one with mild to moderate hypertension taking enalapril 20 mg twice dailyand the other with severe primary h

5、ypertension taking enalaprii 20 mg twice daily (with nifcdipinc30 mg and atenolol 50 mg daily), were given test doses of aspirin 100 and 300 rng daily for 5 daysthe 100-mg dose of aspirin did not alter the efficacy of the antihypertensive drugs, but the 300-mgdose reduced the antihypertensive effica

6、cy 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 andby 91% in those with severe hypertension in contrast, another study in 7 patients with hypertensiontaking enalapri1(mean daily dose 12 9 m

7、g) found that aspirin 81 mg or 325 mg daily for 2 weeks did not have any significanteffect on blood pressuro. 4 a further study in 18 patients also found that aspirin 100 mg daily for2 weeks did not alter the antihypertensive effect of enalapril 20 or 40 mg daily.(c) unspccified ace inhibitorsin a r

8、andoinised study, the use of low-dose aspirin 100 mg daily for 3 months did not alter blood pressurecontrol in patients taking calciumchannel blockers or ace inhibitors, when compared with placebo.similarly, in a rc-analysis of data from the hypertension optimal treatment (hot) study, long-termlow-d

9、ose aspirin 75 mg daily did not interfere with the blood pressure-lowering effects of theanlihypertensive drugs studied, when compared with placcbo. of 18 790 treated hypertensivc patients,about 82% received a calcium-channel blocker, usually felodipine alone or in combination, and 41%received an ac

10、e inhibitor, usually in combination with felodipineb. effects in coronary artery disease and heart failurevarious pharmacological studies have looked at the short-term effects of the combination of aceinhibitors and aspirin on haemodynamic parameters in one study in 40 patients with decompensated he

11、artfailure, aspirin 300 mg given on the first day and 100 mg daily thereafter antagonised the short-termhaemodynamic effects of captopril 50 mg given every 8 hours for 1 days the captopri 1-induced increasein cardiac index and the reduct.ion in peripheral vascular resistance and pulmonary wedge pres

12、sure wereal 1 abolisho止 8 in another study, in 15 patients with chronic heart failure receiving treatment withace inhibitors (mainly enalapril 10 mg twice daily), aspirin in doses as low as 75 mg impairedvasodilatation induced by arachidonic acid.9 in yet another study, aspirin 325 mg daily worsened

13、pulmonary diffusion capacity and made the ventilatory response to exercise less effective in patientstaking enalapril 10 mg twice daily, but did not exert this effect in lhe absence of ace inhibitors 10however, results from studios arc inconsistont. in a review, 11 five of 7 studies reported aspirin

14、 didnot alter the haemodynamic effects of ace inhibitors whereas the remaining two did in one of thesestudies showing an adverse interaction bclwccn aspirin and cnalaprii, ticlopidinc did not interactwith enalapri1a number of large clinical studies of ace inhibitors, mostly post-myocardial infarctio

15、n, have beenre-examined to see if there was a difference in outcome between those receiving aspirin at baseline,and those not the results are sunimarised in "table 2. 29 , (p 15). however, in addition to the problemsof retrospective analysis of non-randomised parameters, the studies vary in the

16、 initialion and durationof aspirin and ace inhibitor treatment and the length of follow-up, the degree of heart failure orischaemia, the prognosis of the patients, and the final end point, (whether compared with placebo orwith the benefits of aspirin or ace inhi bi tors). the conclusions arc therefo

17、re conflicting, and,although two metaanalyses of these studies found no interaction, an editoriall3 disputes the findingsof one of these analyses 14 in addition to these sub-group analyses, there have been a number ofretrospective cohort studies a retrospective study involving 576 patients with hear

18、t failure requiringhospitalisation, showed a trend towards an increased incidence of early readmissions (within 30 daysafter discharge) for heart failure among subjccts treated with ace inhibitors and aspirin, comparedwith those treated with ace inhibitors without aspirin (16% versus 10%) in patient

19、s without coronaryartery disease the in crease in readmissions was statistical ly significant (23% versus 10% ) 15 however,long-term survival in heart failure was not affected by the use of aspirin with ace inhibitorsfurthermore, among patients with coronary artery disease there was a trend towards

20、improvement inmortality 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 involving14 129 elderly patients who survived a hospitalisation for acute myocardial infarction

21、. however, theadded benefit of the combination over patients who received either aspirin or ace inhibitors alonewas not statistically significanlsimilarly, in another cohort of pationts discharged after first hospitalisation for heart failure,there was no increase in mortality rates or readmission r

22、ates in those taking aspirin and aceinhibitors 18 in another retrospective analysis in patients with stable left ventricular systolicdysfunction, no decrease in survival was seen in patients rccciving ace inhibitors, whon comparingthose also receiving aspirin (mean dose 183 mg daily, 74% 200 mg or l

23、ess) and those rxt conversely,an other study found that., compared to patients not taking aspirin, the use of high - dose aspirin (325mg dai ly or more) with an ace inhibitor was associated with a smal 1 but statistical ly significant 3%increase in the risk of death, whereas low-dose aspirin (160 mg

24、 daily or less) was not.c. effects on renal functionacute renal failure developed in a woman taking captopril when she started to take aspirin for arthritisrenal function improved when both were stopped.21 however, in a re-analysis of data fromthe hypertension optimal trcatmont (hot) study, long-ter

25、m low-dose aspirin 75 mg daily had no effecton changes in serum creatinine, estimated creatinine clearanee or the number of patients developingrenal impairmcnt, when compared with placcbo. of 18 790 treated hypertensive patients, 41% receivedan aceinhibitori). phannacokinetic studiesa single-dose st

26、udy in 12 healthy subjects found that the phcirmacokinetics of benazepril 20 mg andaspirin 325 mg were not affected by concurrent usemechanismsome, but not all the evidence suggests that prostaglandins may be involved in the hypotensive action of ace inhibitors, and that aspirin, by inhibiting prost

27、aglandin synthesis, may partially antagoniso the effect of ace inhibitors on blood pressure this effect appears to depend on the dose of aspirin and may also be dependent on sodium status and plasma renin, and therefore it does not occur in all patientsthe beneficial effects of ace inhibitors in hea

28、rt failure and ischaemic heart disease are thought tobe due, in part, to the inhibition of the breakdown of kinins, which are important regulators ofprostaglandin and nitric oxide synthesis such inhibition promotes vasodilatation and afterloadreduction.aspirin may block these ben ef icial effects by

29、 inhibit ing cyclo-oxyge nase (cox) and thus prostag la ndinsynthesis, causing vasoconstriction, decreased cardiac output, and worsening heart, failureimportance and managementlow-dose aspirin (less thein or equal to 100 mg daily) does not alter the antihypertensive efficacyocaptopri1 and cnalapri1

30、no special precautions wou1d therefore seem to be required with aceinhibitors and these low doses of aspirin. a high dose of aspirin (2.4 g daily) has been reported toin teract in 50% of patients in a single study aspirin 300 mg daily has been reported to interact inabout 50% of patients in another

31、study, whereas 325 mg dai ly did not interact in further study. thus,at prosont, it appears that if an ace inhibitor is used with aspirin in doses higher than 300 mg dai ly,blood pressure should be monitored more closely, and the ace inhibitor dosage raised if necessaryintermittent use of aspirinsho

32、uld be considered as a possible cause of erratic control of blood pressure in patients on aceinhibitorsboth ace inhibitors and aspirin are often taken by patients with coronary artery disease, and aceinhibitors are used in chronic heart failure, which is often associated with coron<iry heart dise

33、asethe information about a possible interaction bctwccn ace inhibitors and aspirin in heart failure isconflicting. this may be due to much of the clinical data being obtained from retrospectivenon-randomised analyses il may also be a factor of different disease states for example, aninteraction may

34、be loss likely to be experienced in pationts with heart fai lure of ischaemic aetiologythan those with non-ischaemic causes, because of the added benefits of aspirin in ischaemic heartdisease.24 the avai table data, and its implications, have been extensively reviewed and commentod(n. some commentat

35、ors have advised that, if possible, aspirin should be avoided in patients requiringlong-term treatment for heart failure, particularly if heart failure is severe others suggest avoidingaspirin in heart failure uniess there are clear indications, such as atherosclerosisthe use of lower doses of aspir

36、in (80 to 100 mg daily rather than greater than or equal to 325 mg daily) in those with heart fai lure taking ace inhibitors has also been suggested.24,25,28 us guidelines from 2005 on chronic heart failure33 state that, umany physicians believe the data justify prescribing aspirin and ace inhibitors together when there is an indication for use of aspirin, ” while recognising that not al 1 physicians agree the guidclincs say that further study is ncoded. europe