Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study.
OBJECTIVE
The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country.


METHODS
Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point.


RESULTS
Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment.


CONCLUSIONS
Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.
Mercuri
M
M
Division of Vascular Ultrasound Research, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1025, USA.
Bond
M G
MG
Sirtori
C R
CR
Veglia
F
F
Crepaldi
G
G
Feruglio
F S
FS
Descovich
G
G
Ricci
G
G
Rubba
P
P
Mancini
M
M
Gallus
G
G
Bianchi
G
G
D'Alò
G
G
Ventura
A
A
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016893:Carotid Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology* / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D007558:Italy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D014463:Ultrasonography
D000924:Anticholesteremic Agents; D008055:Lipids; D017035:Pravastatin