Aspirin and Lisinopril: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Aspirin
Lisinopril
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.
You're taking aspirin along with lisinopril, a blood pressure medicine. Aspirin works by blocking substances in the body called prostaglandins. Some of those same substances help your blood vessels relax, which is part of how lisinopril lowers your blood pressure. So in theory, aspirin could make lisinopril work a little less well.
I want to be honest with you: this is mostly a theoretical concern, and the real-world data is not clear-cut. Many people safely take both together, often for good heart reasons. The best move is to keep taking both as prescribed and let your care team check your blood pressure. They can easily manage this by monitoring you and adjusting things if needed.
Effect: Aspirin may blunt the antihypertensive and natriuretic (hyponatremic) effects of lisinopril.
Mechanism: Aspirin inhibits cyclooxygenase-mediated prostaglandin synthesis, reducing vasodilator prostaglandins that partly mediate ACE inhibitor response via the renin-angiotensin pathway. Neither drug is a prodrug requiring activation here.
- Direction: reduced pharmacodynamic effect of lisinopril (blood pressure, sodium handling).
- Evidence: theoretical, inconclusive; clinical relevance debated, likely dose-related.
- Onset: unspecified.
- Management: monitor blood pressure and renal function during concomitant use; individualize therapy. Cardioprotective benefit of aspirin often outweighs risk.
What happens
Reduced hyponatremic and hypotensive effects of ACE inhibitors
Interaction Deep Dive
Exercise caution when aspirin and ACE inhibitors are administered together. Because aspirin has an indirect influence on the renin-angiotensin conversion pathway, giving it alongside ACE inhibitors may lessen the hyponatremic and hypotensive actions of those agents. When the two are combined, patient blood pressure and renal function should be monitored1. Aspirin blocks prostaglandin production, which includes both vasodilator and antithrombotic prostaglandins. In heart failure patients, the generation of vasodilator prostaglandins may serve as a significant counter-regulatory mechanism. Since angiotensin II is capable of stimulating vasodilator prostaglandin production, ACE inhibitors could in theory diminish renal prostaglandin synthesis. Nevertheless, how ACE inhibitors ultimately affect prostaglandin synthesis and platelet aggregability is still a matter of debate, and evidence regarding the aspirin and ACE inhibitor interaction is inconclusive 89. Additional research is required to establish whether this aspirin-ACE inhibitor interaction manifests in patients with hypertension, coronary artery disease, or heart failure, and whether interindividual differences in susceptibility to the interaction may exist. Investigations are also needed to identify the optimal aspirin dose during concurrent ACE inhibitor therapy 10.
Why it happens (mechanism)
Inhibition of prostaglandin synthesis; aspirin-mediated indirect effects on the renin-angiotensin conversion pathway
How to manage this interaction
Good news: this is usually easy for your care team to handle, and combining these two is common and often intentional (for example, protecting the heart).
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Expect your team to check your blood pressure and kidney function from time to time.
- Your lisinopril dose may be adjusted and individualized if your blood pressure isn't well controlled.
Talk with your pharmacist or doctor if you notice higher blood pressure readings, swelling, or big changes in how you feel. Don't stop either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) In patients with severe heart failure, aspirin may hinder the hemodynamic action of ACE inhibitors. In a double blind design, eighteen patients with severe heart failure were randomly assigned to receive placebo, enalapril 10 mg plus placebo, or enalapril combined with aspirin 350 mg. Enalapril given by itself produced a significant reduction in systemic vascular resistance, left ventricular filling pressure, and total pulmonary resistance. Cardiac output was also significantly raised. Once aspirin was included, enalapril produced no significant change in any of these measurements. Aspirin may bring about this effect through interference with prostaglandin synthesis 2.
b) A retrospective subgroup analysis using data from the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) was performed to assess the long-term mortality of patients receiving both aspirin and enalapril after an acute myocardial infarction (AMI). The CONSENSUS II trial included 6090 patients with AMI treated with either enalapril or placebo. In this analysis, the effect of enalapril in patients taking aspirin at the time of randomization was compared with its effect in those not taking aspirin at baseline. Investigators observed that aspirin antagonized enalapril's effect on mortality by the study's conclusion. Additional research is required to verify this interaction and its clinical significance 3.
c) In a randomized, cross-over study, thirteen patients with congestive heart failure (CHF) already on maintenance therapy with an ACE inhibitor received a single dose of captopril 25 mg together with either aspirin 236 mg or placebo. Patients with CHF are known to have elevated plasma concentrations of prostaglandins I2 and E2 (PGI2, PGE2), which possess vasodilating properties. When captopril was given by itself, there was no significant alteration in plasma PGI2 and PGE2 levels, nor in the level of the vasoconstrictor thromboxane A2 (TXA2). However, when captopril was given with aspirin, significant decreases in PGE2 and TXA2 occurred, although the hemodynamic changes were comparable to those observed after captopril alone. These findings suggest that aspirin should be avoided in patients with CHF, particularly when an ACE inhibitor is also being taken 4.
d) In an analysis of mortality data from 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention (BIP) trial, 1247 patients were identified as receiving therapy with an ACE inhibitor. This group was further divided into 618 patients who were also taking aspirin along with an ACE inhibitor and a control group of 579 patients receiving only an ACE inhibitor. Neither the dose or indication of the ACE inhibitor nor the dose of aspirin was documented. After five years, there were 155 deaths (27%) in the control group compared with 119 deaths (19%) in the ACE inhibitor plus aspirin group. Even after adjustment for age, medical history, and other medications, the mortality risk remained lower among 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. Within this subgroup, patients taking aspirin had a lower mortality rate (24%) than those not taking aspirin (34%) after five years. The results of this study conflict with the findings of the SOLVD, CONSENSUS II, GUSTO-I, and GISSI-3 trials, and support 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) caused by idiopathic cardiomyopathy were split into two groups. Group 1 comprised 18 patients receiving an ACE inhibitor (enalapril 20 mg daily), while group 2 consisted of eight patients not on ACE inhibitor therapy. Aspirin 325 mg daily was administered consecutively for eight weeks. Pulmonary function testing was carried out to measure 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 reduced exercise tolerance time, peak exercise oxygen uptake, and tidal volume, and increased the ratio of minute ventilation to carbon dioxide production. Comparable effects were not observed in group 2, who were not receiving an ACE inhibitor. It appears that pulmonary prostaglandin production is heightened in patients with CHF on ACE inhibitor therapy, and the concurrent use of aspirin is detrimental to this process. These findings may be applicable to CHF patients whose condition is due to ischemic heart disease. Whether lower aspirin doses would produce the same adverse effect on ventilatory gas exchange and exercise capacity is not known 6.
f) In certain patients receiving an ACE inhibitor, a dose-related effect of aspirin may negatively influence survival. A retrospective cohort study evaluated 344 patients with a primary discharge diagnosis of CHF at the Institute of Cardiology, University of Milan, from January 10, 1990 to December 31, 1999. The study's outcome variable was death from any cause during the maximum follow-up of 10 years (with an average follow-up of 3.1 years). Patients were categorized into 3 groups according to their 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, comprising 84 (36%) in group 1, 15 (33%) in group 2, and 35 (55%) in group 3. Using the Kaplan-Meier method, survival was comparable in groups 1 and 2, and significantly (p equal to 0.009) worse in group 3. After adjustment for potential confounding factors (including treatment, age, smoking, and diabetes mellitus), a time dependent multivariate Cox proportional hazards regression analysis showed that the combination of an ACE inhibitor and high-dose aspirin was independently associated with the risk of death (hazard ratio, 1.03; p equal to 0.01). The combination of an ACE inhibitor and low-dose aspirin was not associated with mortality (hazard ratio, 1.02; p equal to 0.18). These findings demonstrate a dose-dependent counteraction of aspirin against ACE inhibitors that may affect survival in some patients with CHF 7.
Common questions
Can I take Aspirin and Lisinopril together?
Aspirin may slightly reduce how well lisinopril lowers your blood pressure, but this is theoretical and often not significant; keep taking both as prescribed and let your care team monitor your blood pressure and kidney function. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aspirin and Lisinopril 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 is the Aspirin and Lisinopril interaction managed?
Good news: this is usually easy for your care team to handle, and combining these two is common and often intentional (for example, protecting the heart). Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Expect your team to check your blood pressure and kidney function from time to time. Your lisinopril dose may be adjusted and individualized if your blood pressur… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
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- Can You Take Amla With Lisinopril and Verapamil?
Questions for your pharmacist
- Does my dose of Aspirin or Lisinopril 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. PubMed
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