Thromboxane A2 synthetase inhibition suppresses cough induced by angiotensin converting enzyme inhibitors

Based on our earlier animal study, we became interested to investigate if thromboxane A2 (TXA2) is involved in angiotensin converting enzyme (ACE) induced cough in man. To 11 patients with hypertension, who had developed cough induced by ACE inhibitors, a TXA2 synthetase inhibitor, ozagrel was given for 1 to 2 months together with the ACE inhibitors. One patient developed headache induced by ozagrel and was eliminated from the study after 3 weeks. In other 10 patients, no obvious drug attributable abnormality was observed in subjective and objective symptoms or laboratory tests. In ten patients, cough scores were taken just before and after the administration of a combination of an ACE inhibitor with ozagrel. Median values of cough scores after the combination was significantly (p=0.012) lower than before the combination. Ozagrel reduced cough scores in 5 patients, completely suppressed cough in 3 patients and in 2 of 10 patients, ozagrel did not affect cough scores. Our observations suggest that TXA2 may somehow, mediate coughing induced by the ACE inhibitors. Further, patients on ACE inhibitors who develop cough may benefit from TXA2 synthetase inhibitors.