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. 2025 Mar 13;11(2):143-154.
doi: 10.1093/ehjcvp/pvaf004.

Impact of a personalized, strike early and strong lipid-lowering approach on low-density lipoprotein-cholesterol levels and cardiovascular outcome in patients with acute myocardial infarction

Giuseppe Patti  1   2 , Luca Cumitini  1 , Manuel Bosco  1 , Alessandra Marengo  1 , Domenico D'Amario  1   2 , Marco Mennuni  1   2 , Martina Solli  2 , Leonardo Grisafi  2
Affiliations

Impact of a personalized, strike early and strong lipid-lowering approach on low-density lipoprotein-cholesterol levels and cardiovascular outcome in patients with acute myocardial infarction

Giuseppe Patti et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

Aims: Considering the lack of evidence, we evaluated the impact on cardiovascular outcome of the systematic introduction in our institution of a personalized strike early and strong (SES) approach for lipid-lowering therapy (LLT) in patients admitted for acute myocardial infarction (MI).

Methods and results: We retrospectively analysed data from 500 consecutive patients hospitalized across three periods: Period A (N = 198, January-June 2019), when the low-density lipoprotein cholesterol (LDL-C) goal was <70 mg/dL and a stepwise LLT approach was recommended; Period B (N = 180, January-June 2021), when the LDL-C goal was <55 mg/dL and a stepwise approach was recommended; Period C (N = 122, January-June 2023), when the LDL-C goal was <55 mg/dL and our SES protocol was implemented. Primary endpoints were achievement of the LDL-C goal during follow-up and 1-year incidence of major adverse cardiovascular events (MACE). Compared to the other periods, in Period C, there was a higher use of potent statins, alone or in combination with ezetimibe, and of proprotein convertase subtilisin/kexin type 9 inhibitor inhibitors at discharge. This translated into higher achievement of the LDL-C goal (83% vs. 55% in Period A and 43% in Period B; P < 0.001) and reduced incidence of MACE (3% vs. 12% and 11%; P = 0.026). MACE rates were lowest in patients with early and sustained LDL-C <55 mg/dL and in those achieving both LDL-C <55 mg/dL and ≥50% LDL-C reduction.

Conclusion: The systematic introduction of a personalized, SES strategy for LLT in patients with acute MI led to greater achievement of LDL-C goal and lower risk of MACE at 1 year vs. the stepwise approach.

Keywords: Dyslipidemia; LDL-C; Lipid-lowering therapies; Major adverse cardiovascular events; Myocardial infarction; Strike early and strike strong.

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Figures

Graphical Abstract
Graphical Abstract
The systematic introduction in patients with acute myocardial infarction of a personalized, SES lipid-lowering approach led to greater achievement of the LDL-C goal during follow-up and to lower risk of MACE at 1 year vs. the stepwise approach. LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular events; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SES, strike early and strong.
Figure 1
Figure 1
Personalized flowchart of SES for LLT given during hospitalization/at discharge in patients admitted for acute MI in Period C. Patients on chronic statin treatment and LDL-C <100 mg/dL: The required relative LDL-C reduction to achieve the goal is here < 45%; considering that each statin doubling dose gets approximately 7% of LDL-C decrease and ezetimibe is associated with 20% LDL-C reduction, these patients are treated by increasing statin dose or changing to more potent statin and/or adding ezetimibe. Patients on chronic statin treatment and LDL-C ≥100 mg/dL: In this case, the distance to the goal is ≥ 45% LDL-C decrease, and no modification of oral LLT (increase of statin dose, change of statin type, addition of ezetimibe alone) would be able to get the goal; thus, a fast-track with addition of ezetimibe + PCSK9 inhibitor is performed. Notably, the use of PCSK9 inhibitors in Italy is reimbursed by the National Health System if LDL-C is >70 mg/dL and age is ≤ 80 years. Patients without chronic statin treatment and LDL-C <150 mg/dL: The required relative LDL-C reduction is here < 65%; therefore, these patients are given oral LLT with potent statin at high dose plus ezetimibe if the distance to the goal is > 50% or with potent statin at high dose alone, if the distance to the goal is ≤ 50%. Patients without chronic statin treatment and LDL-C ≥150 mg/dL: In this case, the expected 65% LDL-C reduction achievable with high-intensity statin plus ezetimibe is inadequate to reach the recommended <55 mg/dL LDL-C goal; thus, a fast-track with potent statin plus ezetimibe and PCSK9 inhibitor (triple LLT), resulting in up to 85% LDL-C reduction, is performed. This treatment algorithm applies to all patients with very high cardiovascular risk, but for the purpose of our study, it has been considered in the setting of patients with acute MI. LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; MI, myocardial infarction; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SES, strike early and strong.
Figure 2
Figure 2
LLTs at discharge in the three periods. LDL-C, low-density lipoprotein cholesterol; LLTs, lipid-lowering therapies; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SES, strike early and strong.
Figure 3
Figure 3
Panel A: Comparison of LDL-C levels between the three study periods at discharge, visit 1 and visit 2. Data are expressed as median [interquartile range]. Panel B: individual lowest LDL-C values at follow-up visits in the three periods. Levels of LDL-C at target are marked in evidence. LDL-C, low-density lipoprotein cholesterol; SES, strike early and strong.
Figure 4
Figure 4
Panel A: Prevalence of patients achieving the LDL-C goal in at least one visit during follow-up. LDL-C goal was <70 mg/dL for Period A and <55 mg/dL for Period B and Period C. Panel B: Multivariate analysis for achieving the LDL-C goal in at least one visit during follow-up. LDL-C, low-density lipoprotein cholesterol; PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; SES, strike early and strong.
Figure 5
Figure 5
Panel A: Kaplan–Meier curves for the incidence of MACE at 1 year in the three periods. Panel B: Multivariate analysis for the risk of MACE at 1 year. This analysis highlights that the SES strategy was independently associated with significant reduction in the risk of MACE after adjusting for potential confounders and for variables with different prevalence among patients enrolled in different periods. Older age and left ventricular dysfunction were associated with increased risk. Left ventricular dysfunction was defined as left ventricular ejection fraction < 40%. Chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. ACE, angiotensin-converting enzyme; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular events; SES, strike early and strong.
Figure 6
Figure 6
Panel A: Kaplan–Meier curves for the incidence of MACE at 1 year in patients achieving the LDL-C goal at both follow-up visits (early and sustained LDL-C at target), in those reaching the goal at visit 1, but not at visit 2 (early, but non-sustained LDL-C at target), and in those reaching the goal only at visit 2 or never reaching the goal (late or never LDL-C at target). Panel B: Multivariate analysis for the risk of MACE at 1 year in patients with early and sustained LDL-C at target, in those with early, but non-sustained LDL-C at target and in those with late or never LDL-C at target. LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular events.
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