Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.
BACKGROUND
Until recently, patients with heterozygous familial hypercholesterolemia (HeFH) were considered the best subjects for the assessment of changes in carotid intima-media thickness (cIMT) in randomized intervention trials. Our aims were to investigate whether contemporary statin-treated HeFH patients still show accelerated cIMT increase and to assess the impact of statin treatment, before and after random assignment, on atherosclerosis progression.


RESULTS
We retrospectively evaluated cIMT change, and prior statin treatment and postbaseline LDL-C change as predictors of cIMT change, in 1513 HeFH patients who were randomly assigned to the statin arms of the early ASAP and more recent RADIANCE 1, CAPTIVATE, and ENHANCE studies. In the 3 recent studies combined, mean cIMT increased at only 33%of the rate of the simvastatin-treated patients in the ASAP study (0.014 mm/2 years [95% confidence interval, -0.0003-0.028] versus 0.041 mm/2 years [95% confidence interval, 0.020-0.061]; P<0.05). Patients whose statin therapy could be intensified, as evidenced by an LDL-C decrease after the initiation of on-trial statin therapy, showed cIMT decrease in the first 6 to 12 months and a much lower cIMT increase measured over the full 2 years. In line with this, previously statin-naive HeFH patients showed a lower overall cIMT increase.


CONCLUSIONS
Over the years, intensification of statin therapy in HeFH patients has resulted in an impressive decrease in carotid atherosclerosis progression. In studies that assess other antiatherosclerotic modalities, statin therapy may still induce rapid changes in cIMT. For future cIMT studies, our analyses suggest that patient populations other than intensively pretreated HeFH patients should be selected and that the statin regimen should not be changed on study initiation.
Vergeer
Menno
M
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Zhou
Rong
R
Bots
Michiel L
ML
Duivenvoorden
Raphaël
R
Koglin
Joerg
J
Akdim
Fatima
F
Mitchel
Yale B
YB
Huijgen
Roeland
R
Sapre
Aditi
A
de Groot
Eric
E
Sijbrands
Eric J G
EJ
Pasternak
Richard C
RC
Gagné
Claude
C
Marais
A David
AD
Ballantyne
Christie M
CM
Isaacsohn
Jonathan L
JL
Stalenhoef
Anton F
AF
Kastelein
John J P
JJ
D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009010:Monte Carlo Method; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors