This document summarizes a study examining the effect of statin therapy on the progression of coronary artery calcification. The study found that patients treated with cerivastatin had a significantly lower median increase (8.8%) in coronary calcium scores compared to untreated patients (25% increase). Patients whose LDL cholesterol was reduced to under 100 mg/dl by treatment had an average decrease in calcium scores (-3.4%). The results suggest that statin therapy can slow the progression of calcification and underlying atherosclerosis. However, limitations include the open-label and prematurely ended nature of the study.

1. Editorial Slides
VP Watch – September 11, 2002 - Volume 2, Issue 36
Influence of Statin Therapy on Progression ofInfluence of Statin Therapy on Progression of
Coronary CalcificationCoronary Calcification
Matthew J. Budoff, MD, FACCMatthew J. Budoff, MD, FACC
Assistant Professor of MedicineAssistant Professor of Medicine
Division of CardiologyDivision of Cardiology
Harbor- UCLA Medical Center
Torrance, CA, USA

2. Coronary Calcification
Coronary Calcification has been demonstrated
to be a marker of atherosclerosis and
cardiovascular risk1
Electron Beam Tomography (EBT) is a non-
invasive method to detect and quantify
coronary calcification
Prognostic studies have demonstrated an
increased risk of future cardiac events with
increased coronary calcium scores1

3. Progression of AtherosclerosisProgression of Atherosclerosis
Regression studies have predominantly been
performed with angiographic trials, requiring
multiple invasive angiographic studies
These studies are typically 2-4 years in
duration, demonstrating small but significant
changes, with luminal diameter changing by
microns
It is well known that Luminal stenosis by
angiography poorly quantitates atherosclerotic
burden

4. EBT and ProgressionEBT and Progression
Several studies with EBT have demonstrated
progression of calcium scores of up to 50% per
year2,3,4
Variability of sequential EBT scans has been
demonstrated to range from 8-24% (mean), with
median values of 5-8%5,6
It has been demonstrated that EBT can track
progression of coronary calcium over time, and
progression of CAC has been demonstrated to be
associated with increased cardiovascular risk7,8

5. Progression of CAC and The
Relation to Therapy
(adapted from ref 7)
AUTHOR n KNOWN CAD? No Therapy Statin
Treatment
Type of Therapy
Janowitz 20 No
Yes
18%
27%
-------- ---------
Callister 27 No 44% -------- ---------
Callister 149 No 52%
(n = 44)
5%
(n = 105)
Statins
Maher 81 No 24% -------- ---------
Budoff 299 No 36%
(n = 239)
15%
(n = 60)
Statins
Mitchell 347 No 21% --------- ----------
Brown 160 Yes 40% 20% Simvastatin, Niacin
Achenbach 66 No 25% 8.8% Cerivastatin 0.3
mg/day

6. Annual Event Rate with Progression
of CAC
(Adapted from Reference 8)
0
1.5
6.45
0
1
2
3
4
5
6
7
AnnualEventRates
No progression 1-20% Increase >20% Increase
Annual CAC Score Change Shah et al, AHA 2001

7. Calcium Score progression with
increasing LDL Cholesterol
(Adapted from Reference 2)
+120%
0
–80%
60 120 200
LDL (mg/dL)
Treated Untreated Suboptimal Therapy (LDL >120 mg/dl)
Callister et al. N Engl J Med. 1998;339:1972-1978.
CACScoreChange

8. Achenbach et al, Circulation
2002
66 patients with known high cholesterol
underwent EBT scanning
Baseline calcium scores were 155 mm3
Patients were observed for a mean of 14
months
Follow-up scan revealed score increase to
201 mm3
(25%)

9. Treatment Arm - Cholesterol
Patients were then treated (open label) on
Cerivastatin 0.3 mg/dl for 12 months
Mean LDL was reduced from was 164 mg/dl
to 107 mg/dl (35% reduction, p<0.0001)
Mean HDL increased from 51 mg/dl to 52
mg/dl (1.7% increased, not significant)
Mean Triglycerides decreased from 184 mg/dl
to 152 mg/dl (17%, p=0.004)

10. EBT Changes with Statin Therapy
EBT score increased from 201 mm3
to 203
mm3
Median increase in score (on treatment was
8.8%, significantly lower than no therapy
25%, p<0.0001)
In 32 patients, on-treatment LDL cholesterol
was <100 mg/dl, median change was –3.4%

11. Progression of EBT by LDL
-3.4
8.8
25
-100102030
Annual
Progression
<100 Treated Untreated
TREATMENT LDL
Achenbach, Circulation 2002
P<0.001

12. Study Limitations
Study was stopped prematurely due to
Cerivastatin’s withdrawal from the
marketplace
Open Label study
80% triggering of EBT used (higher variability
than early diastolic trigger)

13. Conclusions:
Cerivastatin significantly reduced rates of
coronary calcium progression
Achieving an LDL cholesterol of <100 mg/dl
was associated with a median decrease of
the coronary calcium burden (-3.4%)
This study correlates with retrospective
studies previously published on EBT that
statin therapy will slow calcification deposition

14. Questions:
Does slowing of the calcification burden correlate
with slowing of the atherosclerotic plaque volume ?
Will helical (fast) CT be able to measure these
changes, given the lower reproducibility due to
slower scan times?10
Will slowing of the coronary calcium burden be
associated with a reduction in cardiovascular
events?

15. References
1. Budoff MJ. Prognostic Value of Coronary Artery Calcification. J Clin Out Manag 2001:8;42-48.
2. Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo NJ. Effect of HMG-CoA Reductase Inhibitors on Coronary Artery Disease as
Assessed by Electron-Beam Computed Tomography. N Engl J Med 1998;339:1972-8.
3. Maher JE, Bielak LF, Raz JA, Sheedy PF, Schwartz RS, Peyser PA. Progression of coronary artery calcification: A pilot study. Mayo
Clin Proc 1999;74:347-355.
4. Budoff MJ, Lane KL, Bakhsheshi H, et al. Rates of progression of coronary calcification by electron beam computed tomography.
Am J Cardiol 2000; 86:8-11.
5. Achenbach S, Ropers D, Mohlenkamp S, et al. Variability of Repeated Coronary Artery Calcium Measurements by Electron Beam
Tomography. Am J Cardiol 2001;87:210-213.
6. Mao SS, Bakhsheshi H, Lu B, Liu SCK, Oudiz RJ, Budoff MJ. Effect of ECG triggering on reproducibility of coronary artery calcium
scoring. Radiology 2001;220(3):707-11.
7. Budoff MJ and Raggi P: Coronary artery disease progression assessed by electron-beam computed tomography. Am J Cardiol
2001;88(suppl):46E-50E.
8. Shah AS, Sorochinsky B, Mao SS, Naik TK, Budoff MJ. Cardiac events and progression of coronary calcium score using electron
beam tomography. Circulation 2000;102;II-604.
9. Achenbach S, Ropers D, Pohle K, et al. Influence of lipid-lowering therapy on the progression of coronary artery calcification: a
prospective evaluation. Circulation. 2002;106(9):1077-82.
10. Qanadli SD, Mesurolle B, Aegerter P, et al. Volumetric quantification of coronary artery calcifications using dual-slice spiral CT
scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm. J Comput Assist Tomogr
2001;25(2):278-286.