Real-world data show early and intensive PCSK9i therapy reduces residual CVD risk in ACS

In an analysis of the retrospective AT-TARGET-IT registry, early and intensive lipid-lowering treatment using PCSK9 inhibitors reduced LDL-c levels and MACE risk at 11 months in hospitalized ACS patients.

This summary is based on the publication of Gargiulo P, Basile C, Galasso G, et al. - Strike early–strike strong lipid-lowering strategy with proprotein convertase subtilisin/kexin type 9 inhibitors in acute coronary syndrome patients: real-world evidence from the AT-TARGET-IT registry. Eur J Prev Cardiol. 2024 May 24:zwae170 [Online ahead of print]. doi: 10.1093/eurjpc/zwae170

Introduction and methods

Background

In patients with ACS, LDL-c lowering reduces CV morbidity and mortality, with a clinical benefit that is proportional to the degree of LDL-c reduction [1]. Current European and American clinical guidelines recommend early initiation of intensive lipid-lowering therapy in this population [2,3]. However, no data are available on implementation of this recommendation in the real-world setting.

Aim of the study

The study aim was to investigate the effects of PCSK9 inhibition started around the time of hospitalization on lipid control and the incidence of MACE in a real-world population of ACS patients.

Methods

The AT-TARGET-IT registry was a multicenter, retrospective, observational, phase 4 study on the use of PCSK9 inhibitors in real-world practice in Italy (n=1836) [4]. The current analysis included 771 hospitalized patients with ACS who were received a prescription for a PCSK9 inhibitor during hospitalization, at discharge, or ≤4 weeks from discharge. Of these 771 patients, 506 (65.6%) were on evolocumab and 265 (34.4%) on alirocumab.

Outcomes

The lipid control endpoint was the percentage of patients reaching the LDL-c target of <55 mg/dL at the first lipid control time point. The clinical endpoint was the incidence of a composite outcome of 4-point MACE (all-cause mortality, nonfatal MI, nonfatal stroke, or ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-c levels at the first lipid control time point.

Main results

Lipid control endpoint

• At hospital admission, the median LDL-c level was 137.0 mg/dL (IQR: 115.0–165.0), which decreased to 43.0 mg/dL (IQR: 23.0–61.0) at the first lipid control time point (median time from baseline: 37 days; IQR: 25–77) and remained virtually unchanged at 49.0 mg/dL (IQR: 28.0–60.5) at the last lipid control time point (median follow-up time: 11 months; IQR: 6–26).
• At the first lipid control time point, 527 of the 771 ACS patients receiving PCSK9 inhibitor treatment (68.3%) achieved the LDL-c target of <55 mg/dL.
• Of these 527 patients, 73 (13.8%) were on statin background therapy alone, 35 (6.6%) received ezetimibe alone, 404 (76.8%) were treated with a combination of a statin and ezetimibe, and 15 (2.8%) were not on other lipid-lowering therapy.
• Of the 771 patients, 608 (78.8%) achieved LDL-c reduction ≥50% at the first lipid control time point and 503 (65.2%) achieved LDL-c <55 mg/dL and LDL-c reduction ≥50%.

MACE endpoint

• During follow-up, the 4-point MACE endpoint (i.e., all-cause mortality, nonfatal MI, nonfatal stroke, or ischemia-driven revascularization) occurred in 116 patients (15.2%), of whom 43 (5.6%) died from any cause, 30 (3.9%) had a recurrent MI, 2 (0.2%) had a stroke, and 41 (5.3%) underwent ischemia-driven revascularization.
• Event curves across LDL-c quartiles showed a stepwise decreased risk of 4-point MACE in patients with lower LDL-c levels at the first lipid control time point (P<0.001) or last lipid control time point (P<0.001).
• During follow-up, patients in the lowest LDL-c quartile (<23 mg/dL) and patients reaching LDL-c <55 mg/dL had lower risks of 4-point MACE, 3-point MACE (i.e., all-cause mortality, nonfatal MI, or nonfatal stroke), and all-cause mortality, compared with those in the higher LDL-c quartiles and those not achieving the LDL-c target, respectively (all P<0.05).

Conclusion

In this analysis of the retrospective, observational, real-world AT-TARGET-IT registry, early and intensive lipid-lowering treatment using PCSK9 inhibitors (strike early–strike strong strategy) reduced LDL-c levels in hospitalized ACS patients, with 68% achieving the guideline-recommended LDL-c target of <55 mg/dL after ~1 month. During a median follow-up time of 11 months, a stepwise decreased risk of MACE with lower LDL-c levels was observed.

Find this article online at Eur J Prev Cardiol.

References

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2. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44:3720–3826.
3. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082–e1143.
4. Gargiulo P, Basile C, Cesaro A, Marzano F, Buonocore D, Asile G, et al. Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: a single country, multicenter, observational study (AT-TARGET-IT). Atherosclerosis 2023;366:32–39.