Annual progression of coronary calcification in trials of preventive therapies: a systematic review

Arch Intern Med. 2009 Dec 14;169(22):2064-70. doi: 10.1001/archinternmed.2009.382.


Background: Coronary artery calcification (CAC) measured by computed tomography is radiographic confirmation of atherosclerosis, predicts cardiovascular events, and has been evaluated as a surrogate measure in randomized trials.

Methods: We performed a literature search for prospective randomized trials in which CAC was measured at baseline and at 1 year or more of follow-up. We computed the weighted mean annualized rate of CAC progression for a variety of therapies tested in these trials.

Results: Ten trials (n = 2612) met our criteria and were included. Electron-beam, double-helix, and multislice computed tomography were used in 6, 2, and 2 trials, respectively. Agatston (8 trials) and volumetric (2 trials) methods were used for CAC evaluation. In 5 trials in subjects with cardiovascular disease (CVD) (n = 2135; age, ~64 years; ~39% women; follow-up, ~26 months), therapies included statins (n = 1370), placebo (n = 564), and antihypertensives (n = 201). In 5 trials in subjects with chronic kidney disease (n = 477; age, ~55 years; ~34% women; follow-up, ~14 months), interventions included low-phosphorus diet (n = 29), sevelamer hydrochloride (n = 229), and calcium-based phosphate binders (n = 219). The mean (SD) weighted annualized CAC increase overall and in patients with CVD and chronic kidney disease was 17.2% (6.7%), 16.9% (5.2%), and 18.4 (11.1%), respectively (P < .001). The rate among those assigned blinded placebo was 14.6% (1.0%) (2 trials). There was no consistent or reproducible treatment effect of any therapy on this outcome measured at 1 year.

Conclusion: The 1-year change in CAC does not appear to be a suitable surrogate end point for treatment trials in patients with CVD or chronic kidney disease.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Calcinosis / diagnostic imaging*
  • Calcinosis / drug therapy
  • Cardiovascular Diseases / prevention & control
  • Coronary Angiography
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / drug therapy
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Tomography, X-Ray Computed