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.......................................................................................................................................................................... 9.5 Patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention Patients who present with ACS are at increased risk of experiencing recurrent CV events. For these patients, lipid management should be undertaken in the context of a comprehensive global risk reduction strategy including lifestyle adaptations, risk factor management, and the implementation of cardioprotective drug strategies. Ideally, patients should be signed up to cardiac rehabilitation programmes to enhance the control of lipid levels434 and improve overall survival following ACS.435 Despite the acknowledged clinical benefits of lowering LDL-C in patients with ACS,436 attainment of LDL-C target values remains suboptimal in this very high-risk setting.437

9.5.1 Lipid-lowering therapy in patients with acute coronary syndromes LDL-C levels tend to decrease during the first days of ACS and therefore a lipid profile should be obtained as soon as possible after admission for ACS. Patients do not have to be fasting as this has little impact on LDL-C levels.100 Lipid-lowering treatment should be initiated as early as possible to increase patient adherence after discharge. Lipid levels should be re-evaluated 46 weeks after ACS to determine whether treatment goals have been achieved and to check for any safety issues; the therapeutic regimen can then be adapted accordingly.

9.5.1.1 Statins. Data from RCTs and meta-analyses indicate that routine early use of high-intensity statin therapy is associated with rapid and sustained clinical benefits.438442 We recommend the initiation of high-intensity statin therapy in all statin-naı ̈ve ACS patients with no contraindication, regardless of initial LDL-C values; the treatment goal is to reach a 50% LDL-C reduction from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL). In those with recurrent events within 2 years while taking maximally tolerated statin therapy, a goal of <1.0 mmol/L (<40 mg/dL) for LDL-C should be considered. The intensity of statin therapy should be increased in those patients receiving low- or moderate-intensity statin treatment at presentation, unless there is a definite history of intolerance to high-intensity statin therapy. The use of lower-intensity statin therapy should be considered in patients at increased risk of adverse effects with highintensity statin therapy, such as in the elderly, patients diagnosed with hepatic or renal impairment, or in the case of a potential risk of drugdrug interactions with other essential concomitant therapies. Regarding the timing of statin treatment initiation, the Statins Evaluation in Coronary Procedures and Revascularization (SECURE- PCI) randomized, placebo-controlled trial recently assessed the impact of peri-procedural loading with atorvastatin [two loading doses of 80 mg, before and 24 h after the planned percutaneous coronary intervention (PCI)] on MACE at 30 days in 4191 patients with ACS and planned invasive management.443 All patients received atorvastatin 40 mg per day starting 24 h after the second loading dose. The authors found no significant treatment benefit in the overall study population. In a pre-specified analysis, a significant 28% relative risk reduction in MACE was observed among patients who underwent PCI (65% of all patients). The benefit was even more pronounced (46% relative risk reduction) in a post hoc analysis including 865 ST-elevation MI (STEMI) patients undergoing reperfusion by primary PCI.443 Based on current evidence, we recommend the initiation of high-intensity statin therapy during the first 14 days of hospitalization for the index ACS.438442 Moreover, pre-treatment (or loading dose for patients already on a statin) with a high-intensity statin should be considered in ACS patients with planned invasive management.443

9.5.1.2 Ezetimibe. In the IMPROVE-IT trial, the addition of ezetimibe to simvastatin therapy provided an additional benefit (6.4% relative risk reduction in the composite clinical endpoint) to post-ACS patients.33 The clinical benefit of adding ezetimibe was consistent across patient subgroups299,444 and also led to a reduction of total CV events,445 stroke,446 and rehospitalizations.447 Patients at higher atherothrombotic risk [as assessed by the TIMI (Thrombolysis In Myocardial Infarction) risk score for secondary prevention] benefitted the most from the addition of ezetimibe.448 In another randomized, open-label trial including 1734 patients with ACS, the addition of ezetimibe to moderate-intensity statin (pitavastatin 2 mg) therapy failed to improve outcomes overall, but did reduce the composite primary endpoint (death, MI, stroke, unstable angina, and ischaemiadriven revascularization) during 3.9-year follow-up in patients with increased intestinal absorption of cholesterol (as assessed by elevated levels of sitosterol)449; however, this finding requires further confirmation.

9.5.1.3 Proprotein convertase subtilisin/kexin type 9 inhibitors. In the FOURIER trial, which included 27 564 patients with atherosclerotic CV disease, the addition of evolocumab to statin therapy (69% highintensity therapy) resulted in a 15% relative risk reduction of the composite primary endpoint throughout a 2.2 year follow-up. Results were consistent in the subgroup of patients with a history of MI (81% of all patients).119,450 A subanalysis of the FOURIER trial showed that patients who achieved the lowest LDL-C values under PCSK9 treatment also had the lowest risk of future MACE.451 In the ODYSSEY Outcomes trial, which included 18 924 patients with recent ACS (112 months prior to enrolment, median 2.6 months), alirocumab added to statin therapy (89% high-intensity therapy) also resulted in a 15% relative risk reduction in the primary composite endpoint and was associated with a 15% relative reduction in allcause mortality throughout a 2.8 year follow-up.120 No serious side effects or safety concerns were reported in these two large trials. The optimal timing of initiating PCSK9 inhibition after ACS and its impact on clinical outcomes remain to be determined. Regarding the timing of PCSK9 inhibitor treatment initiation, post hoc analyses from the FOURIER trial have shown that the closer to the event this is done, the better. Treatment initiation with PCSK9 inhibitors during the acute phase of ACS is under investigation in the EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS) trial.452 Based on current evidence, we recommend the initiation of treatment with PCSK9 inhibitors in patients with ACS who do not reach their respective LDL-C goals (as outlined in Table 7) after 46 weeks of maximum tolerated statin and ezetimibe therapy. In patients who present with an ACS and whose LDL-C levels are not at goal, despite already taking a Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026