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maximally tolerated statin dose and ezetimibe prior to the event, the addition of a PCSK9 inhibitor early after the event (during the hospitalization for the ACS event if possible) should be considered.

9.5.1.4 n-3 polyunsaturated fatty acids. Oral supplementation with highly purified n-3 PUFAs reduced mortality in survivors of MI in one study [Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico-Prevenzione (GISSI-P)] but failed to affect clinical outcomes in subsequent trials using contemporary secondary prevention therapies. A recent meta-analysis of available RCTs showed no reduction in mortality, MI, or major vascular events associated with n-3 PUFAs, including the subgroup of patients with known CAD.453 Therefore, routine treatment with n-3 PUFAs cannot be recommended.

9.5.1.5 Cholesteryl ester transfer protein inhibitors. In 2007, a large prospective study using the CETP inhibitor torcetrapib failed to show any clinical benefit in more than 15 000 high-risk patients, and was potentially harmful.336 The CETP inhibitors dalcetrapib (in >30 000 patients with recent ACS65) and evacetrapib (in >12 000 high-risk patients63) were investigated in 2012 and 2017, respectively. Neither clinical study was able to show any clinical benefit associated with CETP inhibitors.65 More recently, the REVEAL study investigated anacetrapib in >30 000 patients with atherosclerotic vascular disease and resulted in a lower incidence of MACE compared with placebo after 4 years, with no safety concerns.64 However, this compound was not filed for marketing authorization.

9.5.2 Lipid-lowering therapy in patients undergoing percutaneous coronary intervention In a meta-analysis of 13 randomized studies including 3341 patients who were planned to undergo PCI, pre-treatment with a high-dose statin (statin-naı ̈ve patients, 11 studies) or a highdose statin loading dose reduced the risk of MACE (death, MI, or target vessel revascularization) by 44% both for peri-procedural MI and MACE at 30 days.454 In all but one study, PCI was performed in the setting of stable angina or in a non-emergency setting in non-ST elevation ACS (NSTE-ACS). One of the studies that was included in the meta-analysis showed an improvement in coronary flow when primary PCI was used for the treatment of STEMI.455 A routine strategy of either short pre-treatment or loading (on the background of pre-existing therapy) with a high-dose statin before PCI should be considered in elective PCI or NSTE-ACS.454,456,457 In addition, pre-treatment with a statin has also been shown to reduce the risk of contrast-induced acute kidney injury after coronary angiography or intervention.458 Recommendations for lipid-lowering therapy in patients with ACS and patients undergoing PCI are summarized below. Recommendations for lipid-lowering therapy in very-

high-risk patients with acute coronary syndromes

Recommendations Classa Levelb

In all ACS patients without any contraindication or definite history of intolerance, it is recommended that high-dose statin therapy is initiated or continued as early as possible, regardless of initial LDL-C values.438,440,442 I A Lipid levels should be re-evaluated 46 weeks after ACS to determine whether a reduction of >_50% from baseline and goal levels of LDL- C <1.4 mmol/L (<55 mg/dL) have been achieved. Safety issues need to be assessed at this time and statin treatment doses adapted accordingly. IIa C If the LDL-C goal is not achieved after 46 weeks with the maximally tolerated statin dose, combination with ezetimibe is recommended.33 I B If the LDL-C goal is not achieved after 46 weeks despite maximal tolerated statin therapy and ezetimibe, the addition of a PCSK9 inhibitor is recommended.119,120 I B In patients with confirmed statin intolerance or in patients in whom a statin is contraindicated, ezetimibe should be considered. IIa C For patients who present with an ACS and whose LDL-C levels are not at goal, despite already taking a maximally tolerated statin dose and ezetimibe, the addition of a PCSK9 inhibitor early after the event (during hospitalization for the ACS event if possible) should be considered. IIa C

ACS = acute coronary syndrome; LDL-C = low-density lipoprotein cholesterol; PCSK9 = proprotein convertase subtilisin/kexin type 9. aClass of recommendation. bLevel of evidence.

Recommendations for lipid-lowering therapy in veryhigh-risk patients undergoing percutaneous coronary intervention

Recommendations Classa Levelb

Routine pre-treatment or loading (on a background of chronic therapy) with a high-dose statin should be considered in patients undergoing PCI for an ACS or elective PCI.443,454,456 IIa B

ACS = acute coronary syndrome; PCI = percutaneous coronary intervention. aClass of recommendation. bLevel of evidence. Downloaded from academic.oup.com/eurheartj/article/41/1/111/5556353 by guest on 07 October 2026