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252 statin therapy influence on coronary calcification

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252 statin therapy influence on coronary calcification

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.

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