Aspirin Rectal and Enalapril: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Aspirin Rectal
Enalapril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Reduced hyponatremic and hypotensive effects of ACE inhibitors
Interaction Deep Dive
Use caution while using aspirin with ACE inhibitors concomitantly. The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the renin-angiotensin conversion pathway. Monitor blood pressure and renal function of patients when used concomitantly1. Aspirin inhibits the production of prostaglandins, including vasodilator and antithrombotic prostaglandins. The production of vasodilator prostaglandins may be an important counter-regulatory pathway in patients with heart failure. Angiotensin II can stimulate the production of vasodilator prostaglandins, and the use of ACE inhibitors could theoretically reduce renal prostaglandin synthesis. However, the overall effect of ACE inhibitors on prostaglandin synthesis and platelet aggregability remains controversial, and the data on the interaction between aspirin and ACE inhibitors is inconclusive 89. Further studies need to be conducted to determine whether the aspirin-ACE inhibitors interaction occurs in patients with either hypertension, coronary artery disease, or heart failure and whether interindividual susceptibilities to the interaction are likely to be present. Studies to determine the optimal dose of aspirin with concomitant ACE inhibitors therapy also need to be conducted 10.
Why it happens (mechanism)
Inhibition of prostaglandin synthesis; aspirin-mediated indirect effects on the renin-angiotensin conversion pathway
Literature reports
6 reports — tap to read
a) Aspirin may interfere with the hemodynamic effect of ACE inhibitors in patients with severe heart failure. Eighteen patients with severe heart failure were randomized to receive either placebo, enalapril 10 mg and placebo, or enalapril and aspirin 350 mg, in a double blind manner. Enalapril alone significantly decreased systemic vascular resistance, left ventricular filling pressure, and total pulmonary resistance. In addition, cardiac output was significantly increased. When aspirin was added, enalapril did not have a significant effect on any of these values. Aspirin may exert this effect by interfering with prostaglandin synthesis 2.
b) A retrospective subgroup analysis of data from the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) was conducted to determine the long-term mortality of patients on both aspirin and enalapril following an acute myocardial infarction (AMI). The CONSENSUS II study involved 6090 patients with AMI who were treated with enalapril or placebo. In this analysis, the effect of enalapril in patients using aspirin at randomization was compared to the effect of the same drug in those not using aspirin at baseline. Researchers found that aspirin antagonized the effect of enalapril on mortality at the end of the study. More research is needed to confirm this interaction and its health implications 3.
c) In a randomized, cross-over study, thirteen patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an ACE inhibitor were given a single dose of captopril 25 mg with either aspirin 236 mg or placebo. It is known that patients with CHF have increased plasma levels of prostaglandins I2 and E2 (PGI2, PGE2), which have vasodilating capabilities. When captopril was given alone, there was no significant change in the plasma levels of PGI2 and PGE2, or in the level of the vasoconstrictor thromboxane A2 (TXA2.). However, when captopril was administered with aspirin, significant reductions in PGE2 and TXA2 were seen, although the hemodynamic alterations were similar to those seen after captopril was administered alone. These results suggest that the use of aspirin should be avoided in patients with CHF, especially when an ACE inhibitor is also being used 4.
d) In analyzing mortality data from 11,575 patients with coronary artery disease who were screened for the Bezafibrate Infarction Prevention (BIP) trial, a total of 1247 patients were identified who were receiving therapy with an ACE inhibitor. This group was then broken down to 618 patients who were also receiving aspirin in addition to an ACE inhibitor, and a control group of 579 patients who were only receiving an ACE inhibitor. Neither the dose or indication of the ACE inhibitor nor the dose of aspirin were recorded. After five years, there were 155 deaths (27%) in the control group versus 119 deaths (19%) in the ACE inhibitor plus aspirin group. Even after adjustments for age, medical history, and other medications, the risk of mortality was still lower in aspirin users. A subgroup analysis of 464 patients with congestive heart failure (CHF) treated with an ACE inhibitor showed 221 patients (48%) receiving aspirin and 243 patients not receiving aspirin. In this subgroup, patients taking aspirin had a lower mortality rate (24%) than non-aspirin users (34%) after five years. The findings of this study contradict the findings of the SOLVD, CONSENSUS II, GUSTO-I, and GISSI-3 trials, and supports the use of aspirin in patients with coronary artery disease who are also treated with an ACE inhibitor 5.
e) Twenty-six patients with stable congestive heart failure (CHF) due to idiopathic cardiomyopathy were divided into two groups. Group 1 consisted of 18 patients receiving an ACE inhibitor (enalapril 20 mg daily), and group 2 was made up of eight patients not receiving therapy with an ACE inhibitor. Aspirin 325 mg daily was given consecutively for eight weeks. Pulmonary function tests were performed to determine forced expiratory volume in 1 second (FEV1), vital capacity (VC), maximal voluntary ventilation (MVV), and diffusing lung capacity for carbon monoxide (DLCO). In group 1, aspirin decreased exercise tolerance time, peak exercise oxygen uptake and tidal volume, and increased the relation of minute ventilation to carbon dioxide production. Similar effects were not seen in group 2, who were not receiving an ACE inhibitor. It appears as if lung prostaglandin production is enhanced in patients with CHF who are receiving ACE inhibitor therapy, and the coadministration of aspirin is deleterious to this process. These results may be relevant in CHF patients due to ischemic heart disease. It remains unknown whether lower doses of aspirin would have the same negative effect on ventilatory gas exchange and exercise capacity 6.
f) In some patients taking an ACE inhibitor, a dose-related effect of aspirin may adversely affect survival. A retrospective, cohort study evaluated 344 patients with a principal discharge diagnosis of CHF at the Institute of Cardiology, University of Milan, from January 10, 1990 to December 31, 1999. The outcome variable of the study was death from any cause during the maximum follow-up of 10 years (average follow-up was 3.1 years). The patients were classified into 3 groups, based on the use of an ACE inhibitor alone (group 1 (n equal to 235)), an ACE inhibitor with aspirin at a daily dose of 160 mg or less (group 2 (n equal to 45)), or an ACE inhibitor with aspirin at a daily dose of 325 mg or more (group 3 (n equal to 64)). After an average follow-up of 37.6 months, there were 134 (39%) deaths, of which 84(36%) were in group 1, 15 (33%) were in group 2, and 35 (55%) were in group 3. Using the Kaplan-Meier approach, survival was similar in groups 1 and 2, and significantly (p equal to 0.009) worse in group 3. After adjusting for potential confounding factors (including treatment, age, smoking, and diabetes mellitus) a time dependent multivariate Cox proportional hazards regression analysis revealed that the combination of an ACE inhibitor and aspirin at a high dose was independently associated with the risk of death (hazard ratio, 1.03; p equal to 0.01). The combination of an ACE inhibitor and aspirin at a low dose was not related to mortality (hazard ratio, 1.02; p equal to 0.18). These results demonstrate that there is a dose-dependent counteraction of aspirin to ACE inhibitors that may affect survival in some patients with CHF 7.
Common questions
Can I take Aspirin Rectal and Enalapril together?
Reduced hyponatremic and hypotensive effects of ACE inhibitors Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aspirin Rectal and Enalapril interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Aspirin Rectal or Enalapril need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (10)
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Hall D, Zeitler H, & Rudolph W: Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. J Am Coll Cardiol 1992; 20:1549-1555. DOI
- Nguyen KN, Aursnes I, & Kjekshus J: Interaction between enalapril and aspirin on mortality after acute myocardial infarction: subgroup analysis of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). Am J Cardiol 1997; 79:115-119. PubMed
- VanWijngaarden J, Smit AJ, DeGraeff PA, et al: Effects of acetylsalicylic acid on peripheral hemodynamics in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 1994; 23:240-245. DOI
- Leor J, Reicher-Reiss H, Goldbourt U, et al: Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 1999; 33:1920-1925. DOI
- Guazzi M, Pontone G, & Agostoni P: Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors. Am Heart J 1999; 138:254-260. PubMed
- Guazzi M, Brambilla R, Reina G, et al: Aspirin-angiotensin-converting enzyme inhibitor coadministration and mortality in patients with heart failure. Arch Intern Med 2003; 163:1574-1579. DOI
- Cleland JGF, Bulpitt CJ, Falk RH, et al: Is aspirin safe for patients with heart failure?. Br Heart J 1995; 74:215-219. PubMed
- Garcia-Dorado D, Velasco Rami J, Virgos Lamela A, et al: Interaction between antiplatelet agents and ACE inhibitors in patients with acute myocardial infarction. Eur Heart J 1999; 1(suppl F):F24-F28.
- Nawarskas J & Spinler S: Update on the interaction between aspirin and angiotensin-converting enzyme inhibitors. Pharmacotherapy 2000; 20(6):698-710. DOI
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