Association between cough and angiotensin converting enzyme inhibitors versus angiotensin II antagonists: the design of a prospective, controlled study.
BACKGROUND
A common adverse experience in hypertensive patients treated with angiotensin converting enzyme (ACE) inhibitors is a tickling dry cough.


OBJECTIVE
The aim of the present study was to review clinical observations and mechanisms of cough associated with ACE inhibitors. In addition, since the AT1-type angiotensin II antagonists (represented by losartan, MK954, DuP753) are not expected to influence other systems (kinins, prostaglandins) affected by ACE inhibitors, we explored the hypothesis that antihypertensive therapy with these agents will not be associated with cough at a similar frequency or quality to that seen with ACE inhibitors.


METHODS
Patients with a history of an ACE inhibitor-associated dry cough confirmed by a second challenge with lisinopril were enrolled into an international, multicenter, randomly allocated, double-blind, parallel-group, controlled trial, to be treated with losartan, lisinopril or hydrochlorothiazide. The presence and severity of cough were assessed by a self-administered questionnaire and a visual analog scale, respectively.


CONCLUSIONS
It is expected that the new class of antihypertensive agents, angiotensin II antagonists, will not be associated with the high incidence of dry cough associated with the use of ACE inhibitors. It appears that this cough is not related to alterations in the renin-angiotensin system but to kininase II effects.
Lacourcière
Y
Y
Hypertension Research Unit, Le Centre Hospitalier de l'Université Laval, Sainte Foy, Québec, Canada.
Lefebvre
J
J
Nakhle
G
G
Faison
E P
EP
Snavely
D B
DB
Nelson
E B
EB
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D003371:Cough / Q000139:chemically induced*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D017706:Lisinopril / Q000009:adverse effects* / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D011446:Prospective Studies; D012107:Research Design; D011795:Surveys and Questionnaires; D013777:Tetrazoles / Q000009:adverse effects* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D017706:Lisinopril; D019808:Losartan