Long-term probucol treatment prevents secondary cardiovascular events: a cohort study of patients with heterozygous familial hypercholesterolemia in Japan.
The POSITIVE study assessed whether long-term treatment with probucol. a potent anti-oxidant and cholesteryl ester transfer protein (CETP) activator is associated with a lowered risk of cardiovascular events in a very high-risk population: familial hypercholesterolemia (FH).



The study cohort included 410 patients with heterozygous FH, diagnosed between 1984 and 1999 by cardiovascular and metabolic experts at fifteen centers. Traceable patients were screened using predefined eligibility criteria. The primary outcome measure for comparison between probucol exposure and non-exposure was the time to the first cardiovascular event involving hospitalization.



Analysis revealed significant differences in baseline characteristics and follow-up treatment between exposure and non-exposure. An observed indication bias was the use of probucol in more severe FH at diagnosis, both for primary and secondary prevention. When the multivariate Cox regression procedure was used after adjustment for possible confounding factors, probucol lowered the risk (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.050.34) in secondary prevention (n=74) and was statistically significant (p<0.001), although not significant (HR, 1.5; 95% CI, 0.484.67; p=0.49) in primary prevention (n=233). Safety assessment found no specific difference between exposure and non-exposure.



Long-term probucol treatment may prevent secondary attack in a higher cardiovascular risk population of heterozygous FH.
Yamashita
Shizuya
S
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Bujo
Hideaki
H
Arai
Hidenori
H
Harada-Shiba
Mariko
M
Matsui
Shigeyuki
S
Fukushima
Masanori
M
Saito
Yasushi
Y
Kita
Toru
T
Matsuzawa
Yuji
Y
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D007564:Japan; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012306:Risk
D000924:Anticholesteremic Agents; D011341:Probucol