Physicians' Academy for Cardiovascular Education

PCSK9i reduces coronary plaque burden in asymptomatic patients with FH

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study

Literature - Pérez de Isla L, Díaz-Díaz JL, Romero MJ, et al. - Circulation. 2023 Apr 3. doi: 10.1161/CIRCULATIONAHA.122.062557.

Introduction and methods

Background

Patients with FH are at high risk of premature ASCVD, even if they use statins and other lipid-lowering therapies [1]. PCSK9 inhibitors have been shown to reduce the atherosclerotic plaque burden and ASCVD events in patients with previous coronary artery disease [2]. It remains unknown how PCSK9i affect coronary plaque burden in patients with FH.

Aim of the study

The authors investigated the effects of the PCSK9 inhibitor alirocumab on coronary plaque burden and plaque characteristics in asymptomatic patients with FH receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe.

Methods

The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) was a phase IV, open-label, multicenter, single-arm clinical trial. 104 patients (median age 53.3 years, 52% woman) with FH who received optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe were included. Patients were eligible if LDL-c levels <100 mg/dL were not achieved, baseline global coronary plaque burden >30%, and their treating physician prescribed alirocumab. Participants underwent a coronary CTA at baseline, and during follow-up at 78 weeks. During this non-invasive procedure, the entire coronary tree was assessed. Patients received 150 mg of alirocumab subcutaneously every 14 days.

Outcomes

The main end point was the global coronary plaque burden. Secondary end point was the change in coronary plaque characteristics.

Main results

Conclusion

The authors demonstrated that treatment with the PCSK9 inhibitor alirocumab in addition to statin therapy reduced coronary plaque burden and promoted plaque stabilization over a 78 week-study period in asymptomatic patients with FH. The authors highlight that these effects of an PCSK9 inhibitor on atherosclerotic plaques may explain the results obtained with alirocumab in the ODYSSEY OUTCOMES-trial.

References

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Find this article online at Circulation.

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