Patients who have experienced acute coronary syndrome (ACS) are at very high risk for recurrent cardiovascular events, with a 20% chance of recurrence within two years and a five-year mortality rate ranging from 19% to 22%. The risk is particularly high within the first months after the first event.1,2

Effective management of cardiovascular risk factors is crucial for preventing recurrence of cardiovascular events. A strong correlation between low-density lipoprotein cholesterol (LDL-C) levels and the risk of atherosclerotic cardiovascular disease (ASCVD) has been established, with a 22% risk reduction across all major vascular events per 1 mmol/L reduction in LDL-C with statins.3 Consequently, LDL-C reduction is particularly relevant in secondary prevention in patients with a history of ASCVD.1,4,5

Current European Society of Cardiology (ESC) guidelines (2019 ESC/EAS Guidelines for the management of dyslipidemias and 2023 ESC Guidelines for the management of acute coronary syndromes) advocate for a stepwise, LDL-C-guided lipid-lowering therapy (LLT), by prioritizing the achievement of specific LDL-C targets to minimize cardiovascular risk.6,7 For patients at very-high risk, the goal is a therapeutic regimen that achieves ≥50% LDL-C reduction from baseline and an LDL-C goal of <55 mg/dL. These guidelines support a “the lower the better” strategy, emphasizing that lower LDL-C levels are associated with better outcomes, with no evidence of a lower limit for benefit. This strategy encourages early and ongoing treatment adjustments to rapidly achieve and maintain target LDL-C goals.8

High intensity statins (HI-statins) remain the cornerstone of treatment, as the first-line therapy, and increasing statin doses and addition of other lipid-lowering agents, such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, should be prescribed in a stepwise manner if follow-up LDL-C remains above target.7 However, the recommended stepwise approach often falls short, leaving patients with a residual risk.1

In Europe, the percentage of post-ACS patients who reach the recommended LDL-C targets is low, with studies indicating fewer than 20% of patients.9 Despite this, after multiple revisions, ESC/EAS recommendations continue to endorse a stepwise, gradual intensification of lipid-lowering therapy to achieve the LDL-C target.

The latest clinical consensus statement from the Acute Cardiovascular Care (ACVC) program focuses on the importance of early and aggressive LDL-C reduction in patients following an ACS. An alternative “strike early, strike strong” approach, advocated by Krychtiuk et al., involving upfront combination therapy with HI-statins and ezetimibe has been proposed to enhance lipid control and potentially improve outcomes. This strategy is a proactive approach to lipid management that aims to rapidly and substantially lower LDL-C levels after an acute event, before plaque progression and clinical events occur.1 Therefore, evidence supports that a more aggressive approach to lipid management, characterized by the “strike early, strike strong” in addition to “the lower the better”, results in improved LDL-C control and cardiovascular outcomes.8

This study aims to provide a comprehensive analysis of the lipid profiles and discharge LLT of post-MI patients treated at a cardiology department from a district general hospital.

The main finding of the present analysis was that, after ACS, patients with LDL-C on target during follow-up were more frequently receiving combination therapy with HI-statins plus ezetimibe and also demonstrated greater adherence to therapy.

It is important to highlight that the majority of patients (64%) failed to achieve the target LDL-C level by the time of the first follow-up visit, with a median time to reassessment of 6 months. These results fall significantly short of current guideline recommendations, which advise an earlier follow-up within 4–6 weeks to allow timely therapeutic adjustment. In practice, however, such timelines are often unrealistic in most healthcare centers, thereby limiting the rapid escalation of LLT and negatively affecting patient adherence.

Overall, the two groups were comparable in terms of medical history and ASCVD, except for a higher prevalence of hypertension in the LDL-C target group. However, significant differences were observed in terms of metabolic profiles: patients who failed to reach the LDL-C target had a more unfavorable metabolic profile at baseline, which should have justified a more intensive therapeutic approach, with combination therapy at the beginning.

HI-statins were widely prescribed in both groups, in line with current recommendations. However, 37% of patients were prescribed upfront combination therapy with HI-statins and ezetimibe, and this therapeutic approach was more frequently observed in those who achieved the LDL-C target during follow-up. Multivariate analysis demonstrated that this combination was the only independent predictor of success in reaching the LDL-C goal, at least doubling the likelihood of achieving the target.

The significant reduction in LDL-C observed in the <55 mg/dL group, coupled with the higher prescription of combination therapy, suggests that early initiation of HI-statins and ezetimibe may be a key driver of improved lipid control. This finding supports the hypothesis that a more aggressive approach to LLT can lead to better outcomes in post-ACS patients. This proactive strategy emphasizes early and aggressive lipid lowering to rapidly achieve target LDL-C levels and minimize the duration of exposure to elevated LDL-C. It is also noteworthy that some cardiovascular risk factors, namely BMI and active smoking, were reduced between admission and follow-up, suggesting that lifestyle modifications may have contributed to the overall risk reduction in both groups.

Additionally, better adherence in the LDL-C <55 mg/dL group suggests that an intensive regimen may improve long-term medication adherence. Although there were no differences in therapeutic adherence according to LLT strategy, in the LDL-C on target group the higher adherence rate observed further underscores the potential benefits of this approach. Improved adherence may stem from factors such as simplified treatment regimens, favorable safety profile, increased patient education, or a greater perceived benefit of combination therapy.

Nonetheless, 44 (33%) patients treated with the HI-statins–ezetimibe combination still failed to meet the LDL-C goal, including in patients who reported good adherence to this strategy (n=34–79%), thereby remaining at increased risk for recurrent cardiovascular events. These patients would likely benefit from tighter follow-up, more rapid escalation of therapy and combination options to achieve target lipid levels as early as possible.

While current ESC guidelines recommend a stepwise approach to LLT, this study supports the use of a “strike early, strike strong” strategy involving upfront combination therapy with HI-statins and ezetimibe.1

This approach appears to be more effective in achieving LDL-C targets, likely due to the potent LDL-C-lowering effects of this combination when coupled with a favorable safety profile.8

In this cohort, LDL-C attainment was suboptimal with only 36% of post-ACS patients achieving LDL-C levels <55 mg/dL at median 6 months follow-up. Patients with LDL on target were more likely to have started combination therapy with HI-statins plus ezetimibe upon discharge with better adherence and greater LDL-C reductions. These findings support the “strike early, strike strong” approach to LLT as a more effective strategy for achieving LDL-C targets in very high-risk patients.

Some limitations must be acknowledged. This was an observational study; therefore, collected data were limited to medical records. The retrospective, single-center design introduces potential bias, and the relatively small sample size may limit the generalizability of our findings.

Furthermore, the study did not assess long-term clinical outcomes, such as recurrent cardiovascular events or mortality. Data were collected in 2020, before the “strike early, strike strong” recommendation and also before the simplified access to other intensive therapeutic options, like PCSK9i, which may explain the lower prescription of more intensive lipid-lowering strategies. Future prospective studies with larger, more diverse populations are needed to confirm these findings and evaluate the impact of the “strike early, strike strong” approach on clinical outcomes. Such studies should also explore the potential benefits of even lower LDL-C targets, as suggested by recent research.

Ethics Commission for the Health of the Local Health Unit of the Algarve, Registration number: P33/2025.

During the preparation of this work the authors used ChatGPT to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

The authors have no conflicts of interest to declare.