Long-term effects of clinical outcome with low and high dose in the Captopril in Heart Insufficient Patients Study (CHIPS).
BACKGROUND
Although angiotensin-converting enzyme inhibitors are recommended as first line therapy in patients with chronic heart failure, the target doses proven to be effective in major morbidity and mortality trials (e.g. captopril 50 mg b.i.d), are generally not used in daily practice in Belgium.


OBJECTIVE
The objective of this study (CHIPS, Captopril in Heart Insufficient Patients Study) was to compare the long-term effects of a low dose (25 mg b.i.d.) and a high dose (50 mg b.i.d.) of captopril in mild to moderate heart failure. After a titration period of at least 10 days, patients who tolerated 50 mg b.i.d., were randomly assigned to receive either the low dose or the high dose of captopril and followed up to 2 years.


RESULTS
298 patients were included and were followed up for a mean of 12 months. Progression in heart failure seems to be favourably influenced by therapy with high dose in comparison to low dose; a relative difference of 29% in the rates of heart failure worsening was observed between the two doses, 31.5% and 22.4% for low and high dose (p = 0.088), respectively. Treatment with high dose showed also a trend to benefit as compared to low dose in reducing the number of hospitalizations for all causes from 22.4 to 14.5% (p = 0.1) and for congestive heart failure from 14.7 to 7.2% (p = 0.06); moreover, the incidence of fatal and nonfatal cardiac events showed a trend in favour of the high dose of 22% (p = 0.142). The total number of adverse events was comparable for both doses, but dizziness and hypotension were a little more frequently reported in the high-dose group. Serum creatinine values showed no significant changes either in the low-dose or in the high-dose group.


CONCLUSIONS
In the CHIPS-study, in comparison to a low dose, therapy with a high dose of captopril tends to improve the long-term clinical outcome of patients with mild to moderate heart failure without significantly more toxicity.
Clement
D L
DL
Department of Cardiology, University Hospital, Gent, Belgium.
De Buyzere
M
M
Tomas
M
M
Vanavermaete
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D001530:Belgium / Q000453:epidemiology; D002216:Captopril / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril