Temocapril and Aspirin: Interaction Details

a) Aspirin may interfere with the hemodynamic effect of angiotensin converting enzyme 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 ¹. Aspirin should be used cautiously in patients with severe heart failure who are being treated with an angiotensin converting enzyme inhibitor.

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 ².

c) In a randomized, cross-over study, thirteen patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an angiotensin-converting enzyme (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 ³.

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 angiotensin-converting enzyme (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 ⁴.

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 ⁵.

f) A summary of recently published literature investigating the clinical significance of an interaction between aspirin and angiotensin converting enzyme inhibitors (ACEIs) in patients with cardiovascular diseases was performed. After reviewing much of the data two generalizations are made: dosage of aspirin of 100 mg/day or less does not appear to affect prostaglandin production and thus interact little with ACEIs, whereas higher doses have a higher risk, and some patients may, for an unknown reason, be more susceptible to this interaction. It is postulated, although still not entirely understood, that inhibition of prostaglandin synthesis by aspirin is the major mechanism by which aspirin may negate the benefits of ACEIs. The possibility also exists that ACEIs negate the benefits of aspirin by ACEI-induced increases in prostaglandins nullifying the decrease in prostaglandins seen with aspirin ⁸.