Clinical study
Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic Mediterranean population: The Carotid Atherosclerosis Italian Ultrasound Study*

https://doi.org/10.1016/S0002-9343(96)00333-6Get rights and content

Purpose

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.

Patients and 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 ≠ 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 ( ± 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.

References (31)

  • CrouseJR et al.

    Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLACII)

    Am J Cardiol

    (1995)
  • WattsGF et al.

    Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St. Thomas' Atherosclerosis Regression Study (STARS)

    Lancet

    (1992)
  • HolmeI et al.

    Risk factors and raised atherosclerotic lesions in coronary and cerebral arteries

    Arteriosclerosis

    (1981)
  • HertzerNR et al.

    Coronary angiography in 506 pa-tients with extracranial cerebrovascular disease

    Arch Intern Med

    (1985)
  • RubensJ et al.

    Individual susceptibility to extracranial carotid atherosclerosis

    Arteriosclerosis

    (1988)
  • CravenTE et al.

    Evaluation of the association between carotid artery atherosclerosis and coronary artery atherosclerosis

    Stroke

    (1990)
  • HerringtonDM et al.

    Strong correlation between carotid artery wall thickness and quantitative coronary artery angiography assessment of coronary atherosclerosis

    Circulation

    (1994)
  • PignoliP et al.

    Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging

    Circulation

    (1986)
  • MercuriM

    Noninvasive imaging protocols to detect and monitor carotid atherosclerosis progression

    Am J Hypertens

    (1994)
  • ARICInvestigators

    The Atherosclerosis Risk in Communities (ARIC) study: design and objectives

    Am J Epidemiol

    (1989)
  • O'LearyDH et al.

    On behalf of the CHS Collaborative Research Group. Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study

    Stroke

    (1991)
  • SalonenJT et al.

    Risk factors for carotid atherosclerosis: the Kuopio Ischaemic Heart Disease Risk Factors Study

    Ann Med

    (1989)
  • BotsML et al.

    Cardiovascular determinants of carotid artery disease. The Rotterdam Study

    Hypertension

    (1992)
  • SirtoriCR et al.

    Pravastatin intervention trial on carotid artery atherosclerosis in patients with mild hypercholesterolemia: the CAIUS study

    Int J Cardiac Imag

    (1995)
  • Cited by (254)

    • The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study: Rationale and Trial Protocol

      2017, Journal of Stroke and Cerebrovascular Diseases
      Citation Excerpt :

      Third, the study drug in this trial, pravastatin, is not a strong but rather a traditional statin. In addition, its daily dose of 10 mg is lower than that in the previous trials on statins and carotid IMT in Western countries (generally 40 mg daily).6-8 In Japanese, 10 mg daily of pravastatin seems to greatly reduce the LDL cholesterol level, although it is not certain if this dose is enough for stabilization of carotid plaque.

    • Changing characteristics of statin-related cIMT trials from 1988 to 2006

      2016, Atherosclerosis
      Citation Excerpt :

      While results from several clinical trials have indicated that lipid-lowering therapy (LLT) significantly reduced progression of cIMT [8–12], a meta-analysis of LLT trials showed no relationship of cIMT change to CVD risk [5]. In early clinical trials, statin effects on cIMT changes were positive and clinically relevant [8,13–19]; however, in some recent trials, cIMT change did not differentiate between lipid-lowering therapies where a difference would be expected based on existing clinical outcomes data [20,21], including the recently reported IMPROVE-IT trial [22,23]. It has been suggested that the predictive power of cIMT as a surrogate marker for assessment of CVD risk may be limited in some settings due to differences in trial design, cIMT methods, and patient characteristics [24–26].

    View all citing articles on Scopus
    *

    CAIUS was funded through independent research grants provided by Bristol-Myers Squibb S.p.A. Italy, and in part by a grant from the Italian National Research Council (C.N.R. Progetto Finalizzato, Invecchiamento, SP321).

    Prof. Giancario Descovich is deceased.

    View full text