CAC score can identify REDUCE-IT-eligible patients who benefit most from icosapent ethyl

Association between REDUCE-IT criteria, coronary artery disease severity, and cardiovascular events: the Western Denmark Heart Registry

Literature - Mortensen MB, Dzaye O, Razavi AC, et al. - Eur J Prev Cardiol. 2022 Jun 3:zwac104. doi: 10.1093/eurjpc/zwac104.

Introduction and methods

Background

Recently, the REDUCE-IT trial showed that treatment with 2 g icosapent ethyl twice daily reduces the risk of ASCVD in patients treated with a statin who have high triglyceride concentration but low to moderate LDL-c concentration [1]. The REDUCE-IT trial included a heterogeneous sample of patients treated as part of primary or secondary prevention. It remains unknown which patients with elevated triglycerides may benefit most from treatment with icosapent ethyl. Because coronary artery calcium (CAC) is strongly associated with the risk of ASCVD [2], the CAC score could potentially help identify patients who would benefit most from treatment with icosapent ethyl.

Aim of the study

The aim of this study was to determine whether ASCVD risk stratification based on CAC score among REDUCE-IT-eligible patients is useful in identifying patients who would benefit most from treatment with icosapent ethyl.

Methods

The researchers used data from the Western Denmark Heart Registry of 2146 adults in whom CT angiography had been performed during the period January 1, 2008-December 31, 2017, and who would have been eligible to participate in the REDUCE-IT trial based on biochemical criteria – triglyceride concentration of 1.52-6.63 mmol/L and LDL-c concentration ≥1.06 mmol/L and ≤2.59 mmol/L. CT angiography was used to determine whether patients had no CAD (luminal stenosis of 0% and Agatston score of 0), non-obstructive CAD (luminal stenosis <50%) or obstructive CAD (luminal stenosis >50%). The following CAC scores were used as a measure of calcified atherosclerotic plaque burden: 0, 1-299, and ≥300.

Outcomes

The researchers were interested in the risk of ASCVD events, defined as myocardial infarction, stroke, revascularization, or all-cause mortality more than 90 days after CT angiography. Hard ASCVD events were defined as myocardial infarction, stroke, or all-cause mortality. Median follow-up was 4.3 years.

Main results

  • The incidence of ASCVD events increased stepwise as the CAC score increased: 10.5 per 1000 person-years for patients with a CAC score of 0, 18.7 per 1000 person-years for patients with a CAC score of 1-299, and 49.8 per 1000 person-years for patients with a CAC score ≥300.
  • Patients with a CAC score ≥300 had an increased risk of ASCVD events, compared with patients with a CAC score of 0 (HR: 3.1; 95%CI: 1.9-4.9); for patients with a CAC score of 1-299, the risk was not significantly higher (HR: 1.4; 95%CI: 0.9-2.0).
  • Patients with obstructive CAD had an increased risk of ASCVD events, compared with patients without CAD (HR: 2.9; 95%CI: 2.0-4.2); for patients with non-obstructive CAD, the risk was not significantly higher (HR: 1.3; 95%CI: 0.8-2.3).
  • In patients with and without obstructive CAD, CAC score identified patients at lower or higher risk of ASCVD similarly.
  • Overall, the estimated 5-year NNT was 45, but ranged from 17 (for patients with a CAC score ≥300) to 87 (for patients with a CAC score of 0).
  • In patients with non-obstructive CAD and high CAC scores the NNT to prevent hard ASCVD event was lower than for patients with obstructive CAD and lower CAC scores.

Conclusion

This study of a cohort of patients undergoing CT angiography and who met REDUCE-IT criteria showed that the CAC score, a measure of atherosclerotic plaque burden, can be used to determine which patients will benefit most from treatment with icosapent ethyl, regardless of whether they have obstructive or non-obstructive CAD.

References

1. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

2. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008;358:1336-1345.

Find this article online at Eur J Prev Cardiol.

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