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

Since coronary artery and cerebrovascular diseases are the most common serious complications of long standing hypertension, there is a great potential for combining treatment with aspirin and angiotensin-converting enzyme inhibitors (ACE-1). However, the data regarding interaction of aspirin and ACE-1 in relation to blood pressure control and survival benefits are controversial and inconclusive. We presumed that the appearance of dry cough in some of the patients following initiation of ACE-1 treatment could be used as a marker for the presence of their influence, whereas ACE-1 cough attenuation after addition of aspirin to treatment could be a sign of aspirin and ACE-1 interaction on clinical level. The present study was aimed to use ACE-1 induced cough as a clinical marker of ACE-1 activity to determine whether dose-dependent aspirin and ACE-1 interaction does exist. In a cohort of 750 consecutive ACE-1 treated hypertensive and postinfarction outpatients we identified 78 (10.4%) non-smoking ACE-1 related coughers. Out of them, 31 (21 men, 10 women; mean age 61 +/- 0.9 years) agreed to take part in the study, which was aimed to compare two regimens of combined ACE-1 and aspirin treatment (self-matched control data): intermediate (500 mg daily) vs low-dose aspirin (100 mg daily). On each visit the life quality, cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin demonstrated an excellent safety profile and did not influence any life quality score and ACE-1 induced cough. In contrast, intermediate doses completely abolished cough in 17 patients and reduced coughing in other 11 patients. Cough severity and cough frequency scores decreased, respectively, from 2.7 +/- 1.1 to 0.7 +/- 1.2 (P < 0.001) and from 7.1 +/- 2.3 to 2.0 +/- 2.2 (P < 0.0001). Overall, the cough frequency score method alone could identify a clear modification of cough in 26 (84%) patients, and cough severity score method alone in 24 (77%). Using the combined frequency/severity score method a modification of cough could be identified in 28 (90%) of the patients receiving intermediate dose of aspirin. Aspirin did not influence heart rate and blood pressure control either in hypertensives or in postinfarction patients. We conclude that using ACE-1 induced cough as a clinical marker of ACE-1 activity demonstrates that an interaction between ACE-1 and aspirin at 500 mg/day does exist. We did not find any evidence supporting the presence of a clinically significant interaction between ACE-1 and aspirin at 100 mg/day. Thus, combined treatment by low dose aspirin and ACE-1 seems to be both safe and useful.