Comparison of losartan with ACE inhibitors and dihydropyridine calcium channel antagonists: a pilot study of prescription-event monitoring in Japan.
BACKGROUND
Two pilot studies for prescription-event monitoring in Japan (J-PEM) were launched in 1997 and 1998. Here we present data regarding adverse events that were reported in the second pilot J-PEM study where losartan was compared with ACE inhibitors and dihydropyridine calcium channel antagonists.


METHODS
We conducted a cohort study with a concurrent control. METHODS/PATIENT GROUP: Study subjects prescribed losartan, an ACE inhibitor or a calcium channel antagonist were identified from prescriptions in hospital or community pharmacies. Events and other information were collected from doctors and pharmacists by mailed questionnaires. Events were coded and analysed using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Crude event rates were calculated and compared between patients treated with losartan and those receiving control drugs. When the difference was statistically significant, the event was further examined in several ways, including follow-up studies and by comparison with the data of the UK PEM study on losartan.


RESULTS
Pharmacists were sent 4344 questionnaires and returned 3591 (83%), while doctors were sent 3517 questionnaires and returned 1380 (39%). In the doctors' data, the adverse event rate for losartan treatment was greater than that for ACE inhibitors and/or calcium channel antagonists for the following seven events: headache, palpitations, anaemia, insomnia, feeling abnormal, increased blood pressure and asthma. Most of these are known adverse drug reactions (ADRs) of losartan except for two events: increased blood pressure and asthma. In pharmacists' data, the event rate for losartan was significantly greater than that for control drugs for the following ten events: hot flushes, abnormal hepatic function, oedema, peripheral swelling, decreased blood pressure, increased blood pressure, rhinitis, contact dermatitis, dry skin and heat rash. The first five events were known ADRs of losartan but the other five were not. When the two sets of data were combined, the rate of an additional event, increased blood creatinine phosphokinase, which is a known ADR of losartan, was significantly greater than that for the control drugs. The six events that were not documented as ADRs for losartan were not judged to be ADRs based on the results of follow-up studies and comparison with the UK PEM study on losartan. The crude rate of cough with losartan treatment was similar to that with calcium channel antagonists, but was significantly less than that with ACE inhibitors.


CONCLUSIONS
No novel safety problems were found in this observational cohort study on losartan. The rates of some known ADRs differed significantly between patients treated with losartan and those in the control groups.
Samizo
Kazuo
K
Department of Pharmacoepidemiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Kawabe
Eri
E
Hinotsu
Shiro
S
Sato
Tsugumichi
T
Kageyama
Shigeru
S
Hamada
Chikuma
C
Ohashi
Yasuo
Y
Kubota
Kiyoshi
K
D000368:Aged; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003371:Cough / Q000139:chemically induced; D004095:Dihydropyridines / Q000009:adverse effects*; D016903:Drug Monitoring / Q000379:methods / Q000706:statistics & numerical data; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D007564:Japan; D019808:Losartan / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011795:Surveys and Questionnaires
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D019808:Losartan