Does Aspirin Attenuate the Beneficial Effects of Angiotensin-Converting Enzyme Inhibition in Heart Failure?

Abstract

Ischemic heart disease is the most common underlying cause of congestive heart failure, and thus aspirin (acetylsalicylic acid [ASA]) and angiotensin-converting enzyme (ACE) inhibitors are commonly used together for treatment in this setting. The issue of possible attenuation of the effect of ACE inhibitors by ASA has been an area of intense debate. Currently, it is perceived that a significant part of the beneficial effect of ACE inhibitors is related to augmentation of bradykinin levels, which among other effects stimulate the release of prostacyclin. Aspirin, on the other hand, inhibits the production of prostacyclin by blocking cyclooxygenase. Prostaglandins play an important endogenous vasodilatory role and counteract the enhanced peripheral vasoconstriction state in congestive heart failure. Thus, the counteracting effect of ASA on the augmentation of prostacyclin synthesis by ACE inhibitors could result in a potential reduction of the beneficial effects of the ACE inhibitor's and could be of great importance. This article reviews reports from large clinical trials pertaining to this issue and relates their findings to the currently available theoretical bases for support of the counteracting effect of ASA on augmentation of prostacyclin synthesis by ACE inhibitors. The clinical implications of such an interaction are discussed.

The Platelet in Diabetes

“…In the 3,577 patients with diabetes in the HOPE study, treatment with ramipril (10 mg/day) lowered the risk of MI, stroke, or CV death by 25% (P ϭ 0.0004)-an effect that persisted after adjustments were made for changes in systolic and diastolic blood pressures (49). By blocking prostaglandin synthesis, aspirin has been hypothesized to blunt the bradykinin-related vasodilatory effects of ACE inhibitors (50). Clinical data on the interaction of aspirin with ACE inhibitors have been mixed; retrospective analyses of two large heart failure trials suggested that aspirin blunted the benefit achieved with ACE inhibitor treatment (50).…”

Renal Considerations in Angiotensin Converting Enzyme Inhibitor Therapy

“…Finally, it is unclear as to the extent to which aspirin therapy makes the CHF patient more susceptible to ACE inhibitor-associated renal failure. 54,55 Hyperkalemia Hyperkalemia is relatively common in ACE inhibitor-treated patients with CHF or uremia. Fortunately, increases in plasma potassium are generally fairly modest (Յ1 mEq/L), and severe hyperkalemia with ACE inhibitors is uncommon.…”

Clinical evidence of dose-dependent interaction between aspirin and angiotensin-converting enzyme inhibitors

“…29,30 In general, prostaglandins play an important endogenous vasodilatory role and counteract the enhanced peripheral vasoconstriction state in hypertension and congestive heart failure. 31 It was suggested, that inhibition of PG synthesis by aspirin may result in vasoconstriction and might reduce the beneficial effects of ACE-I on blood pressure and heart failure management. 31 …”

“…31 It was suggested, that inhibition of PG synthesis by aspirin may result in vasoconstriction and might reduce the beneficial effects of ACE-I on blood pressure and heart failure management. 31 …”

“…31 Another source for the discrepancies between results may be related to the fact that systemic ACE concentrations do not necessarily reflect tissular concentrations. 33 A possible explanation for the current controversies may be based on that interactions between ACE-I and aspirin are dose-dependent: a combination of partial agonism and antagonism between aspirin and ACE-I at multiple levels may explain the complex dose-dependent interrelationship between these agents.…”