CAC helps to identify people who will benefit from NOAC for primary prevention of ASCVD

Usefulness of Coronary Artery Calcium to Identify Adults of Sufficiently High Risk for Atherothrombotic Cardiovascular Events to Consider Low-Dose Rivaroxaban Thromboprophylaxis (From MESA)

Literature - Arps K, Rifai MA, Blaha MJ, et al., - Am J Cardiol 2019, doi: 10.1016/j.amjcard.2019.07.016

Introduction and methods

The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulant Strategies) demonstrated a role for low-dose rivaroxaban in patients with stable ischemic heart disease [1]. Most myocardial infarctions, up to 70%, occurs in people without established atherosclerotic CVD (ASCVD) [2]. The COMPASS strategy can potentially be beneficial in those in the primary prevention setting with comparable atherosclerotic risk as in the COMPASS trial [3-5]. Because anticoagulation therapy is associated with harm (increased risk of bleeding), appropriate risk stratification is important in primary prevention setting.

This study examined whether individualized risk assessment, using coronary calcium score (CAC) and traditional risk estimation, identified a high-risk population, who benefit from low-dose rivaroxaban for primary ASCVD prevention.

The effect of low dose rivaroxaban was modeled in the Multi-Ethnic Study of Atherosclerosis (MESA). The MESA is a prospective, multicenter study consisting of a multi-ethnic population free of clinical ASCVD at baseline, not using antiplatelet or anticoagulant therapy. The MESA cohort included 6814 participants between July 2000 and September 2002. 10-year ASCVD risk was calculated using the Pooled Cohort Equations (PCE) [6] and CAC was calculated by the Agatston method. ASCVD was a composite of CV death, non-fatal MI or non-fatal stroke. Relative risk ratios from COMPASS were applied to absolute event rates in the MESA cohort to calculate NNT and NNH, stratified by ASCVD risk and baseline CAC.

Main results

  • Composite outcome was higher in those with CAC ≥300 compared to those with CAC 0 (20.1 events/1000 person-years vs. 2.7 events/1000 PY; HR:2.9, 95%CI: 2.03-4.25, P<0.001). CAC provided further risk information within 10-year ASCVD risk subgroups.
  • Estimated 5-year NNT with rivaroxaban was 75 in those with CAC 100- <300 and NNT was 45 in subjects with CA ≥300.
  • There was no association between CAC and bleeding outcome.
  • Estimated 5-year NNH was 252 with CAC 100- <300 and NNT was 98 with CAC ≥300.
  • Risk stratification by CAC resulted in greater separation of risk curves than risk stratification by 10-year ASCVD risk.
  • 2-year and 5-year net benefit, using the relative risk reduction of 20% for net-clinical benefit by low dose rivaroxaban in the COMPASS trial, was highest in those with CAC ≥100. Estimated 5-year net benefit was 85 with CAC 100- <300 and 49 with CAC ≥300.


Assessing atherosclerotic burden by CAC in people without established ASCVD, in addition to 10-year ASCVD risk calculation, helps to identify a high-risk population who will benefit from low dose rivaroxaban.


1. Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med 2017;377:1319–1330.

2. Miedema MD, Cohn JN, Garberich RF, et al. Underuse of cardiovascular preventive pharmacotherapy in patients presenting with ST-elevation myocardial infarction. Am Heart J 2012;164:259–67.

3. Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018;6736:1–11.

4. The ASCEND Study Collaborative, Bowman L, Mafham M, et al. The ASCEND Study Collaborative Group. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med 2018;379:1529–1539.

5. McNeil JJ, Woods RL, Nelson MR, et al. Effect of Aspirin on Disability-free Survival in the Healthy Elderly. N Engl J Med 2018;379:1499–1508.

6. Goff DC, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935–59.

Find this article online at Am J Cardiol

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