Annual Progression of Coronary Calcification in Trials of Preventive Therapies: A Systematic Review

OBJECTIVES: 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.

CONCLUSIONS: 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. 

PMID: 20008688

Posted in Computed Tomography and tagged , , , , , , , .


  1. It is important to differentiate the well established role of calcium scoring in cardiovascular risk assessment, and the potential use of CAC as an endpoint in pharmacological interventional trials.

  2. An editorial comment accompanies this paper:

    A double take on serial measurement of coronary artery calcification.
    O’Malley PG.
    Arch Intern Med. 2009 Dec 14;169(22):2051-2

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