Interaction between aspirin and ACE Inhibitors: resolving discrepancies using a meta-analysis

Recently, studies have attempted to explore the interaction between ACE inhibitors and aspirin (acetylsalicylic acid) when both drugs are used concomitantly to reduce mortality in patients with coronary artery disease. Results have been conflicting due, in part, to sub-optimal methods used to explore this interaction.

We reviewed systematically all studies on mortality in patients treated with ACE inhibitors and aspirin and conducted a meta-analysis in order to explore the interaction between both drugs and resolve discrepancies. To be included, each study had to provide data on mortality of patients who received both drugs, either drug and no drug. These data were necessary to calculate the synergy index (S) and its 95% confidence interval (CI) that we used to quantify the effect due to interaction between ACE inhibitors and aspirin. After testing for heterogeneity of effects, we pooled the S values from the individual studies into one summary measure. Subsequently, we compared our results with those obtained through the most common but incorrect method of evaluating interaction. This method uses significance testing of the relative risk of mortality when a 'product term' between ACE inhibitors and aspirin is entered in a logistic regression model.

Eight studies met the inclusion criteria. The pooled synergy index S indicates slight but precise antagonism between ACE inhibitors and aspirin (S = 0.91; 95% CI 0.80 to 1.03). In contrast, the pooled 'product term' is not significant and would have lead to the conclusion of absence of interaction (p = 0.15).

There seems to be an antagonistic interaction between ACE inhibitors and aspirin. Former discrepancies were due to inadequate assessment of interaction. Results from the Studies on Left Ventricular Dysfunction (SOLVD) and Heart Outcome Prevention Evaluation (HOPE) trials that assessed the effect of combined administration of ACE inhibitors and aspirin were not included in this meta-analysis because those trials did not provide enough data to compute the S statistic. It is possible that results from on-going trials such as Women's Atovarstatin Trial on Cholesterol (WATCH) will shed more light on ACE inhibitor and aspirin interaction in the future.