请讨论：阿司匹林对ACEI降压作用的影响

众所周知，非甾体类解热镇痛药抑制COX，从而抑制前列环素的合成。这类药物同血管紧张素转换酶抑制剂(简称ACEI)合用时可降低ACEI的降压作用，引起患者血压波动，尤其是吲哚美辛。由于阿司匹林在心血管疾病患者中的广泛应用，使得患者同时使用阿司匹林与ACEI类降压药的几率大大增加。因此，想和大家讨论一下阿司匹林对ACEI降压作用的影响，这种影响究竟有多大？是不是对所有的ACEI类药物都有影响，还是只对某几个药物有影响？长期服用阿司匹林是否会增加还是减弱对ACEI的影响？阿司匹林多大剂量时没有影响？药师面对这种问题该如何正确处理？

欢迎大家发表各自的看法。

这个问题两年前曾经研究过，当时看了很多资料，我试着解答一下
阿司匹林有两个作用，一为抑制环氧化酶  使TXA2合成降低， （TXA2 作用为加速血小板聚集）从而阻止血栓形成
第二个作用为抑制PGI2的合成，  PGI2 为一抗凝因子，与TXA2作用相反，阿司匹林对二者的作用强度为1大于2，而且低剂量的阿司匹林主要抑制第一个作用，只有高剂量的阿司匹林才对二者皆有作用，一般阿司匹林每日剂量小于0.18克时，才有抗血栓的作用  所以ACEI联合阿司匹林用药时，只有患者每日剂量大于0.18克时候，才需要监测血压

非常好的一个话题！非常有道理的解释！
学习了！

我检索的资料是：卡托普利与小剂量阿司匹林(75 mg／d)联用对其降压作用无明显影响，但与每天300 mg阿司匹林联用则其降压作用明显减弱，可能与每天300 mg阿司匹林阻断了血管内PGI2的生成有关。

对其他ACEI药物的影响国内则未见相关文献报道。
参考文献：

学习了，附件的内容很好

学习学习，内容不错，收获挺大，谢谢

学习了,非常好的话题,非常感谢!

谢谢!非常好！
大家赶快来看一看

今天读了Stockley's Drug Interactions 8th Edition，其中阿司匹林与ACEI的相互作用有详细的说明，供大家参考：
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, there was no increase in mortality rates or readmission rates in those taking aspirin and ACE inhibitors.18 In another  retrospective analysis in patients with stable left ventricular systolic dysfunction, no decrease in survival was seen in patients receiving ACE inhibitors, when comparing those also receiving aspirin (mean dose 183 mg daily, 74% 200 mg or less) and those not. Conversely, another study found that, compared to patients not taking aspirin, the use of high-dose aspirin (325 mg daily or more) with an ACE inhibitor was associated with a small but statistically significant 3% increase in the risk of death,  Whereas low-dose aspirin (160 mg daily or less) was not.
C. Effects on renal function
Acute renal failure developed in a woman taking captopril when she started to take aspirin for arthritis. Renal function improved when both were stopped.21 However, in a re-analysis of data from the  hypertension Optimal Treatment (HOT) study, long-term low-dose aspirin 75 mg daily had no effect on changes in serum creatinine, estimated creatinine clearance or the number of patients developing renal impairment, when compared with placebo. Of 18 790 treated hypertensive patients, 41% received an ACE
inhibitor.
D. Pharmacokinetic studies
A single-dose study in 12 healthy subjects found that the pharmacokinetics of benazepril 20 mg and aspirin 325 mg were not affected by concurrent use.
Mechanism
Some, but not all the evidence suggests that prostaglandins may be involved in the hypotensive action of ACE inhibitors, and that aspirin, by inhibiting prostaglandin synthesis, may partially antagonise 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 patients.
The beneficial effects of ACE inhibitors in heart failure and ischaemic heart disease are thought to be due, in part, to the inhibition of the breakdown of kinins, which are important regulators of prostaglandin and nitric oxide synthesis. Such inhibition promotes vasodilatation and afterload reduction.
Aspirin may block these beneficial effects by inhibiting cyclo-oxygenase (COX) and thus prostaglandin synthesis, causing vasoconstriction, decreased cardiac output and worsening heart failure.
Importance and management
Low-dose aspirin (less than or equal to 100 mg daily) does not alter the antihypertensive efficacy of captopril and enalapril. No special precautions would therefore seem to be required with ACE inhibitors and these low doses of aspirin. A high dose of aspirin (2.4 g daily) has been reported to interact in 50% of patients in a single study. Aspirin 300 mg daily has been reported to interact in about 50% of patients in another study, whereas 325 mg daily did not interact in further study. Thus, at present, it appears that if an ACE inhibitor is used with aspirin in doses higher than 300 mg daily, blood pressure should be monitored more closely, and the ACE inhibitor dosage raised if necessary. Intermittent use of aspirin
should be considered as a possible cause of erratic control of blood pressure in patients on ACE inhibitors.
Both ACE inhibitors and aspirin are often taken by patients with coronary artery disease, and ACE inhibitors are used in chronic heart failure, which is often associated with coronary heart disease.
The information about a possible interaction between ACE inhibitors and aspirin in heart failure is conflicting. This may be due to much of the clinical data being obtained from retrospective non-randomised  analyses. It may also be a factor of different disease states. For example, an interaction may be less likely to be experienced in patients with heart failure of ischaemic aetiology than those with non-ischaemic causes, because of the added benefits of aspirin in ischaemic heart disease.24 The available data, and its implications, have been extensively reviewed and commented on.Some commentators have advised that, if possible, aspirin should be avoided in patients requiring long-term treatment for heart failure, particularly if heart failure is severe. Others suggest avoiding aspirin in heart failure unless there are clear indications, such as atherosclerosis.
The use of lower doses of aspirin (80 to 100 mg daily rather than greater than or equal to 325 mg daily) in those with heart failure taking ACE inhibitors has also been suggested.24,25,28 US guidelines from 2005 on chronic heart failure33 state that, “Many physicians believe the data justify prescribing aspirin and ACE inhibitors together when there is an indication for use of aspirin,” while recognising that not all physicians agree. The guidelines say that further study is needed. European guidelines state that there is little evidence to support using ACE inhibitors and aspirin together in heart failure. The guidelines say aspirin can be used as prophylaxis after prior myocardial infarction, but that it should be avoided in patients with recurrent hospitalisation for worsening heart failure.
NICE guidelines in the UK make no comment about the combination of ACE inhibitors and aspirin. They say that all patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor, and that aspirin (75 to 150 mg once daily) should be prescribed for patients with the combination of heart failure and atherosclerotic arterial disease (including coronary heart disease).35 Data from ongoing randomised studies may provide further insight. Until these are available, combined low-dose aspirin and ACE inhibitors may continue to be used where there is a clear indication for both.
An increased risk of deterioration in renal function or acute renal failure appears to occur rarely with the combination of aspirin and ACE inhibitors.
The routine monitoring of renal function, which is advised with ACE inhibitors, should be sufficient to detect any interaction.

阿司林的预防用量是75-150,治疗量是300又如何理解?