Interaction between angiotensin-converting enzyme inhibitors and aspirin: a review

Aspirin and angiotensin-converting enzyme inhibitors (ACEIs) are often asso ciated for the treatment of coronary disease and/or chronic heart failure, but conclusions of some prospective and retrospective studies show a possib le negative interaction between aspirin and ACEIs. ACEIs inhibit the conver sion of angiotensin I to angiotensin II and also the catabolism of bradykin in, which results in increased synthesis of vasodilatory agents [prostaglan dins and nitric oxide (NO)], whereas aspirin inhibits prostaglandin synthes is. Thus, a potential interaction from the opposing effects of aspirin and ACEIs could affect the metabolism of bradykinin. We conducted an extensive Medline search, as well as a manual search, of published literature includi ng pharmacodynamic studies and clinical trials concerning the impact of asp irin on the effect of ACEIs in hypertension, coronary disease and chronic h eart failure. A review of this literature shows five studies in hypertensio n (all prospective and using blood pressure as the main criterion of assess ment), five in coronary disease (three retrospective and two prospective tr ials, four of which use mortality as the criterion of assessment) and 13 in chronic heart failure (eight using haemodynamic measurements of which seve n are prospective - one prospective study using pulmonary tests, four using clinical events including mortality as criterion of assessment of which tw o are prospective). The counteraction of ACEI efficacy by aspirin is demons trated in one out of five studies in hypertension, one out of four of studi es in coronary disease and nine out of thirteen in chronic heart failure. T his counteraction is more often observed with high dosages of aspirin (grea ter than 250 mg/day, four out of six studies) and less often with lower dos ages (less than or equal to 250 mg/day, three out of II studies). These stu dies are retrospective analyses or use haemodynamic end-points, so there is as yet no methodological argument strong enough to contraindicate the aspi rin-ACEI association or to prove the clinical relevance of this interaction . In conclusion, prospective studies using mortality as a criterion of asse ssment are needed to offer the practitioner the answer to the question of A CEI-aspirin association.