title: Clinical evidence of dose-dependent interaction between aspirin and angiotensin-converting enzyme inhibitors.
abstract: 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-I). However, the data regarding interaction of aspirin and ACE-I 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-I treatment could be used as a marker for the presence of their influence, whereas ACE-I cough attenuation after addition of aspirin to treatment could be a sign of aspirin and ACE-I interaction on clinical level. The present study was aimed to use ACE-I induced cough as a clinical marker of ACE-I activity to determine whether dose-dependent aspirin and ACE-I interaction does exist. In a cohort of 750 consecutive ACE-I treated hypertensive and postinfarction outpatients we identified 78 (10.4%) non-smoking ACE-I 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-I 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-I 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-I induced cough as a clinical marker of ACE-I activity demonstrates that an interaction between ACE-I and aspirin at 500 mg/day does exist. We did not find any evidence supporting the presence of a clinically significant interaction between ACE-I and aspirin at 100 mg/day. Thus, combined treatment by low dose aspirin and ACE-I seems to be both safe and useful.
authors.affiliation: Cardiac Rehabilitation Institute, The Chaim Sheba Medical Center, Tel-Hashomer, and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: E Z
authors.initials: EZ
authors.lastname: Fisman
authors.forename: E
authors.initials: E
authors.lastname: Grossman
authors.forename: M
authors.initials: M
authors.lastname: Motro
authors.forename: A
authors.initials: A
authors.lastname: Tenenbaum
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003371:Cough / Q000139:chemically induced; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D001241:Aspirin