Secondary prevention after acute coronary syndrome

Overview and definitions

Abbreviations used on this page

ESC 2023 calls secondary prevention after acute coronary syndrome (ACS) central to quality of life and to lowering morbidity and mortality.^[1] It says prevention should start as early as possible after the index event.^[1] For detail it points to the 2019 ESC chronic coronary syndromes and 2021 ESC prevention guidelines, and it summarises targets in its Figure 17.^[1] That 2019 chronic coronary syndromes guideline is now dated: the 2024 ESC chronic coronary syndromes guideline updates and replaces it.^[17] Current chronic coronary syndrome care is taught in the Chronic coronary syndromes topic.

ACC/AHA 2025 aims its lipid rows at recent ACS, meaning within 12 months.^[2] It says the 2023 AHA/ACC chronic coronary disease guideline provides more detailed recommendations on long-term lipid management after prior ACS.^[2] ACC/AHA 2025 does not define when a patient moves from ACS to chronic coronary syndrome, largely because no data exist to guide any recommendations.^[2]

Strength labels differ by body. ESC rows carry a Class and Level, and ACC/AHA rows a class of recommendation (COR) and level of evidence (LOE).^[1][2] NHFA/CSANZ 2025 GRADE rows carry a strength of recommendation and a certainty of evidence, while its consensus rows are labelled consensus.^[5] Acute loading doses, reperfusion and invasive timing belong to the ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS topics.

Classification: ESC 2023 long-term treatment groups, and risk labels used for antithrombotic and lipid decisions

ESC 2023 Figure 17 sorts long-term treatment after ACS into three groups.^[1]

• Support healthy lifestyle choices: smoking cessation, healthy diet, regular exercise and healthy weight.^[1]
• Continue optimal pharmacological and cardio-protective treatment: psychosocial management, antithrombotic therapy, lipid-lowering therapy and annual influenza vaccination, plus other treatments as appropriate, while promoting drug adherence and persistence.^[1]
• Reach and sustain risk factor treatment targets (set out under Investigations below).^[1]

The same figure lists discharge on cardio-protective medications, starting lifestyle management and referral to cardiac rehabilitation (CR).^[1] It adds an outpatient review to manage comorbidities and discuss patient goals and preferences.^[1]

The first risk label is high bleeding risk (HBR).^[1] ESC 2023 says HBR should be assessed in a structured manner, for example one major or two minor ARC-HBR characteristics.^[1] ARC-HBR stands for the Academic Research Consortium high bleeding risk criteria.^[2] ACC/AHA 2025 lists them for patients after percutaneous coronary intervention (PCI).^[2] At least 1 major or 2 minor criteria helps to identify increased bleeding risk.^[2]

ARC high bleeding risk criteria after PCI (ACC/AHA 2025 Table 22, complete)

^[2]

The second label is ischaemic risk.^[1] ESC 2023 uses high and moderate ischaemic risk, each without HBR, to grade adding a second antithrombotic agent to aspirin for extended long-term secondary prevention.^[1] For lipids, the 2026 ACC/AHA dyslipidemia guideline says that ASCVD at very high risk includes the following.^[6] The majority of patients with clinical ASCVD are likely to be at very high risk, it says.^[6]

• A history of multiple major ASCVD events: ACS within the past 12 months, history of myocardial infarction (MI) other than that ACS, history of ischaemic stroke, or symptomatic peripheral artery disease;^[6]
• or 1 major ASCVD event and multiple high-risk conditions: age over 65 years, coronary artery revascularisation, current smoker, diabetes, history of heart failure (HF), hypertension, or LDL-C over 100 mg/dL despite maximally tolerated statin plus ezetimibe.^[6]

^[1]

Epidemiology: how much risk is left after discharge

^{[2] [3] [1]}

ESC/EAS 2025 says patients with ACS are at particularly elevated risk of recurrent cardiovascular events, especially within the first year after discharge.^[3] It calls the early post-ACS period the most vulnerable phase after a major coronary event.^[3] ACC/AHA 2025 says event rates are substantially higher after recent ACS than in chronic coronary disease.^[2] That higher risk, it says, supports more aggressive LDL-C targets in recent ACS than in chronic coronary disease.^[2]

Who is most exposed?^[2] ACC/AHA 2025 names women, traditionally underrepresented racial and ethnic groups, and patients who needed intensive care during their index hospitalisation as at particular risk of readmission.^[2] Moderate to severe CKD (stages III–V) affects more than 30% of ACS patients (ESC 2023).^[1] Patients with ACS and concomitant CKD receive less interventional and pharmacological treatment and have a worse prognosis than patients with normal kidney function (ESC 2023).^[1] Age is a major predictor of adverse outcomes, yet patients aged 75 or more are often under-represented in trials (ESC 2023).^[1] The NHFA/CSANZ 2025 guideline summary records marked inequities in ACS management and outcomes in Australia.^[5]

Treatment gaps are documented too.^[1] ESC 2023 reports adherence of 50% in primary prevention and 66% in secondary prevention.^[1] CR referral, participation and implementation are low (ESC 2023).^[1] ACC/AHA 2025 adds that referral is low especially for women and traditionally underrepresented groups.^[2] Many patients with ACS do not reach target LDL-C, for reasons including underprescribing, cost and intolerance (ACC/AHA 2025).^[2]

Pathophysiology: the rationale behind selected treatments

^{[2] [1]}

Thrombosis and bleeding over time

ACC/AHA 2025 describes a sustained prothrombotic state after ACS.^[2] That, it says, is why antithrombotic therapy continues beyond the index presentation.^[2] Prolonged DAPT causes excess bleeding, which may lead to DAPT interruption.^[2] Interruption in turn may increase recurrent ischaemic events.^[2] After PCI for ACS, ischaemic and bleeding events both markedly decrease over time (ESC 2023).^[1]

LDL cholesterol: lower is better

In ACC/AHA 2025, benefit from LDL-C-lowering drugs is proportional to the degree of LDL-C lowering.^[2] Each 1.0 mmol/L (about 39 mg/dL) LDL-C reduction gives about a 22% relative reduction in cardiovascular events over 4 to 5 years.^[2] The NHFA/CSANZ 2025 summary says each 1.0 mmol/L reduction is associated with a 20% lower risk of major cardiovascular events.^[5] ESC/EAS 2025 sums up the timing argument as the sooner, the lower, the better.^[3]

Inflammation, haemodynamics and infection

ESC 2023 says inflammation plays a central role in atherosclerosis and acute coronary events.^[1] Colchicine reduces neutrophil adhesion to endothelial cells and platelets (ACC/AHA 2025).^[2] It has also been shown to reduce high-sensitivity C-reactive protein and low-attenuation plaque volume on aspirin and statin.^[2]

Beta-blockers lower myocardial oxygen demand by reducing heart rate, blood pressure and contractility (ACC/AHA 2025).^[2] SGLT2 blockade causes glycosuria and lowers glucose without hypoglycaemia, with falls in weight and blood pressure (ESC 2023).^[1] ESC 2023 says its benefits may relate more to cardio-renal haemodynamic effects than to atherosclerosis.^[1] Influenza infection may contribute to atherogenesis and plaque destabilisation, precipitating ACS (ACC/AHA 2025).^[2]

Clinical assessment before discharge and at follow-up

ACC/AHA 2025 Table 21 (Guidance for ACS Discharge: Best Practices) includes these clinical-assessment, referral and social-determinant items (selected rows; the table also covers communication and patient or caregiver assessment).^[2]

• Address comorbidities and risk factors for recurrent events.^[2]
• Assess for ongoing ischaemic symptoms, using a standardised instrument ideally embedded in the electronic health record.^[2]
• Assess risk for bleeding related to medications or the procedural site.^[2]
• Assess the need for additional testing (for example, repeat echocardiogram or staged PCI).^[2]
• Assess whether vaccinations are current (for example, influenza).^[2]
• Perform medication reconciliation, including a prescription for sublingual nitroglycerin unless contraindicated.^[2]
• Confirm referral to CR and provide CR educational materials with contact information.^[2]
• Assess and address barriers to obtaining and taking medicines and to attending CR, including the viability of home-based or hybrid CR.^[2]

Why screen the mind?^[1] Heart disease carries a two-fold risk of anxiety and mood disorders (ESC 2023).^[1] Depression, anxiety and psychological stress are associated with worse outcomes.^[1] After an ACS event, ESC 2023 says, anxiety and depression are frequently encountered and raise the risk of non-adherence to medications and lifestyle changes, subsequent MACE and death.^[1] Cognitive impairment can occur as a complication of ACS, and some patients may have difficulty with care instructions at discharge (ESC 2023).^[1]

In older patients, ESC 2023 recommends routine frailty assessment (for example, the Rockwood Frailty Score) to aid decisions.^[1] It recommends routine comorbidity assessment (for example, the Charlson index) as well.^[1]

Differential diagnosis: when the plan seems to be failing

Statin intolerance is common in practice, and its most commonly reported cause is statin-associated muscle symptoms (ACC/AHA 2025).^[2] Before escalating or switching, check for these explanations.

Explanations to check, and how the sources describe them

^{[2] [1]}

ACC/AHA 2025 Table 18 diagnoses pericarditis from pleuritic chest pain plus at least 1 criterion.^[2] It describes post-MI pericarditis as rare, at 0.1%–0.5% in the era of early reperfusion.^[2]

• A pericardial friction rub on auscultation.^[2]
• ECG evidence such as classic PR-segment depression or diffuse concave ST-segment elevation, or, in the setting of MI, persistent ST-segment elevation or dynamic T-wave changes.^[2]
• A new or growing pericardial effusion on echocardiography.^[2]

Investigations and targets

Lipids

ACC/AHA 2025 recommends a lipid profile as soon as feasible after presentation with ACS.^[2] The reason: LDL-C falls modestly from 24 hours after symptom onset.^[2]

^{[1] [2]}

Left ventricular function and sudden-death prevention

ACC/AHA 2025 assesses LVEF before discharge to guide therapy and for risk stratification, and ESC 2023 uses a pre-discharge LVEF of 40% or less to trigger reassessment for a primary prevention implantable cardioverter defibrillator (ICD).^[2][1]

• ESC 2023: in patients with a pre-discharge LVEF of 40% or less, repeat evaluation of LVEF 6–12 weeks after an ACS (and after complete revascularisation and the institution of optimal medical therapy) is recommended to assess the potential need for sudden cardiac death primary prevention ICD implantation (Class I, Level C).^[1]
• ESC 2023: cardiac magnetic resonance imaging should be considered as an adjunctive imaging modality to assess the potential need for primary prevention ICD implantation (Class IIa, Level C).^[1]
• ACC/AHA 2025: in patients post MI, ICD implantation is recommended in selected patients with an LVEF of 40% or less at least 40 days post MI and at least 90 days after revascularisation, to reduce death (COR 1, LOE A).^[2]
• ACC/AHA 2025 Table 17 selection (all patients with expected survival of 1 year or more): LVEF 30% or less with New York Heart Association (NYHA) class I, II or III; LVEF 31%–35% with NYHA class II or III; or LVEF 40% or less with inducible ventricular tachycardia.^[2]

Risk factor targets (ESC 2023 Figure 17)

Treatment goals shown in ESC 2023 Figure 17

^[1]

Management: items tied to the index admission and discharge

Initiating guideline-recommended therapies in hospital strongly predicts adherence at 6 months (NHFA/CSANZ 2025 guideline summary).^[5] ESC 2023 starts lipid lowering early for prognosis and to increase adherence after discharge.^[1] The items below are tied to the index admission or to discharge; they form a checklist rather than a sequence.^[1][2]

• Statin: ESC 2023 recommends high-dose statin therapy initiated or continued as early as possible, regardless of initial LDL-C values (Class I, Level A); NHFA/CSANZ 2025 says to initiate before hospital discharge, and continue indefinitely, the highest tolerated statin dose unless contraindicated or completely statin intolerant (strong recommendation, high certainty).^[1][5]
• Lipid intensification for patients already on therapy: ESC 2023 recommends intensifying lipid-lowering therapy during the index ACS hospitalisation for patients on lipid-lowering therapy before admission (Class I, Level C).^[1]
• CR referral: ACC/AHA 2025 says patients with ACS should be referred to an outpatient CR program before hospital discharge to reduce death, MI and hospital readmissions and to improve functional status and quality of life (COR 1, LOE A); NHFA/CSANZ 2025 says to refer all people with ACS to a multidisciplinary exercise-based cardiac rehabilitation program before discharge (strong recommendation, moderate certainty).^[2][5]
• Influenza vaccine: ESC 2023 says it should be given preferentially during the index hospitalisation, during influenza season, for those not protected by a seasonal vaccination.^[1]
• Smoking: ESC 2023 says smoking-cessation interventions should begin during hospitalisation, combining behavioural interventions, pharmacotherapy and counselling.^[1]
• LVEF: ACC/AHA 2025 recommends assessing LVEF before discharge to guide therapy and for risk stratification (COR 1, LOE C-LD).^[2]
• Discharge information: ESC 2023 says it should be provided in written and verbal formats before discharge, and that preparation using the teach-back technique and/or motivational interviewing, giving information in chunks and checking understanding, should be considered (Class IIa, Level B).^[1]

ACC/AHA 2025 Table 20 lists the essential components of patient education.^[2]

• Reason for hospitalisation (reason for admission, diagnostic tests, procedural results).^[2]
• Tailored discussion of lifestyle modifications (AHA Life’s Essential 8).^[2]
• Medications: written and verbal instructions including purpose, dose, frequency and potential adverse effects of each medication; refill instructions; changes to the prehospital regimen; importance of adherence.^[2]
• Symptom management: what to monitor for and actions to take should symptoms recur, including whom to call.^[2]
• Returning to daily routine: when to resume physical activity, sexual activity, work and travel.^[2]
• Psychosocial considerations: open dialogue about symptoms of depression and anxiety.^[2]
• Follow-up care: future appointments with cardiology, CR and additional testing after discharge.^[2]

^{[1] [2]}

Management: antithrombotic therapy

^{[1] [2] [5]}

The ESC 2023 default: DAPT for 12 months

After PCI, ESC 2023 says a default DAPT regimen is generally recommended for 12 months.^[1] That regimen is a potent P2Y12 receptor inhibitor (prasugrel or ticagrelor) plus aspirin, irrespective of stent type, unless contraindicated.^[1] By default, ESC 2023 recommends this DAPT for a minimum of 12 months after an ACS event.^[1] The exceptions include urgent surgery, an indication for oral anticoagulation (OAC), and bleeding risk too high for other reasons.^[1]

ACC/AHA 2025 gives its own aspirin and duration rows.^[2]

• In patients with ACS, an initial oral loading dose of aspirin, followed by daily low-dose aspirin, is recommended to reduce death and MACE (COR 1, LOE A); the dosing table gives a maintenance dose of 75–100 mg orally daily (non-enteric coated).^[2]
• In patients with ACS who are not at high bleeding risk, DAPT with aspirin and an oral P2Y12 inhibitor should be given for at least 1 year to reduce MACE (COR 1, LOE A).^[2]
• In patients with a history of stroke or transient ischaemic attack, prasugrel should not be given because of worse net clinical outcomes (COR 3: Harm, LOE B-R).^[2]

ACC/AHA 2025 oral antiplatelet maintenance doses (NSTE-ACS, non-ST-elevation ACS; loading doses are in the acute-care topics)

^[2]

Shortening or de-escalating within the first 12 months

ESC 2023 keeps 12-month DAPT, preferably with prasugrel or ticagrelor, as the default.^[1] Shortened and de-escalated strategies should only be used as alternatives, in general to reduce bleeding.^[1] ESC 2023 notes that much of the evidence on these strategies in ACS comes from trials powered primarily for bleeding outcomes.^[1] Many had a non-inferiority design and were not powered for differences in ischaemic outcomes.^[1]

Bleeding-reduction strategies in the first 12 months (ESC 2023 Rec Table 6 shortening/de-escalation group complete; ACC/AHA 2025 rows 2–5)

^{[1] [2]}

Who needs a PPI? ESC 2023 Table 7, Suggested strategies to reduce bleeding risk related to PCI, lists PPIs in patients on DAPT at higher-than-average risk of gastrointestinal bleeds.^[1]

• A history of gastrointestinal ulcer or haemorrhage, anticoagulant therapy, or chronic non-steroidal anti-inflammatory drug or corticosteroid use;^[1]
• or two or more of: age 65 years or more, dyspepsia, gastro-oesophageal reflux disease, Helicobacter pylori infection, chronic alcohol use.^[1]

PPIs that inhibit CYP2C19, particularly omeprazole and esomeprazole, may blunt the pharmacodynamic response to clopidogrel (ESC 2023).^[1] There is no strong evidence that this increases ischaemic events or stent thrombosis in trials and propensity-matched studies.^[1] No interaction between PPIs and aspirin, prasugrel or ticagrelor has been observed.^[1]

What does the trial evidence look like?^[1] In a large network meta-analysis, 3-month but not 6-month DAPT was associated with more MI or stent thrombosis in ACS (ESC 2023).^[1] ACC/AHA 2025 says several randomised trials have consistently shown that aspirin withdrawal followed by ticagrelor monotherapy after 1 to 3 months of ticagrelor-based DAPT results in less bleeding without clear excess in MACE, compared with continued DAPT, in patients with ACS undergoing PCI.^[2] Although those studies had relatively low rates of ischaemic events, study-level and individual patient data pooled analyses gave similar results (ACC/AHA 2025).^[2] Data with clopidogrel have been mixed, and ACC/AHA 2025 notes concern that clopidogrel monotherapy started 1 to 2 months after PCI may increase the risk of MACE in patients with ACS compared with longer DAPT.^[2]

• STOPDAPT-2-ACS (ESC 2023 description): ACS patients were randomised at 1–2 months to clopidogrel monotherapy or continued DAPT for 12 months; non-inferiority for the composite of cardiovascular or bleeding events was not proven, suggesting that systematic very short DAPT (under 3 months) followed by clopidogrel monotherapy is not a useful strategy in ACS.^[1]
• MASTER DAPT (ESC 2023 description): 4579 HBR patients (49% ACS, 12% STEMI) undergoing PCI with a bioabsorbable polymer-coated stent received abbreviated DAPT (1 month) followed by aspirin or P2Y12 inhibitor monotherapy, or DAPT for 3 months or more; net adverse clinical events and major adverse cardiac or cerebral events were comparable, and major or clinically relevant non-major bleeding was significantly reduced with the abbreviated strategy.^[1]

Beyond 12 months

NHFA/CSANZ 2025 adds these long-term antiplatelet rows.^[5] Its Figure 6 legend notes that current Pharmaceutical Benefits Scheme criteria preclude the prescription of ticagrelor as single therapy.^[5]

• After a completed course of DAPT (1–12 months), prescribe a long-term P2Y12 inhibitor over aspirin (strong recommendation, moderate certainty).^[5]
• In people who remain at high ischaemic and low bleeding risk, consider long-term DAPT beyond 12 months (weak recommendation, moderate certainty).^[5]

ACS with an indication for oral anticoagulation

Long-term OAC is indicated in 6–8% of patients undergoing PCI (ESC 2023).^[1] After ACS the indication should be re-assessed, and OAC continued only if a compelling indication exists.^[1] In atrial fibrillation (AF) without mechanical valves or moderate to severe mitral stenosis, ESC 2023 favours non-vitamin K antagonist oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) because they reduce bleeding.^[1]

• ESC 2023 examples of a compelling indication: paroxysmal, persistent or permanent AF with a CHA2DS2-VASc score of 1 or more in men and 2 or more in women; a mechanical heart valve; or recent or a history of recurrent or unprovoked deep vein thrombosis or pulmonary embolism.^[1]

ACC/AHA 2025 and NHFA/CSANZ 2025 give parallel rows.^[2][5] ACC/AHA 2025 prefers a direct oral anticoagulant (DOAC) over a VKA for most patients.^[2] It generally favours clopidogrel because prasugrel and ticagrelor trials excluded patients needing long-term anticoagulation.^[2] The Australian Figure 7 legend says people receiving triple therapy should be given a proton pump inhibitor.^[5]

• ACC/AHA 2025: in patients with ACS who require oral anticoagulant therapy, aspirin should be discontinued after 1 to 4 weeks of triple antithrombotic therapy, with continued use of a P2Y12 inhibitor (preferably clopidogrel) and an oral anticoagulant to reduce bleeding risk (COR 1, LOE B-R).^[2]
• NHFA/CSANZ 2025: in people discharged after an ACS with an indication for long-term OAC therapy, continue OAC and DAPT (preferentially aspirin and clopidogrel) for 1–4 weeks, then cease aspirin (strong recommendation, high certainty).^[5]
• NHFA/CSANZ 2025: in the same people, cease antiplatelet therapy at 6–12 months and continue anticoagulation alone (strong recommendation, moderate certainty).^[5]

Management: lipid lowering

ESC 2023 sets the secondary-prevention goal at LDL-C below 1.4 mmol/L (below 55 mg/dL) with a 50% or greater reduction from baseline.^[1] It recommends that a high-intensity statin (for example, atorvastatin or rosuvastatin) is initiated as early as possible after hospital admission, preferably before planned PCI, and prescribed up to the highest tolerated dose to reach the LDL-C goals.^[1]

^{[1] [2]}

The 2025 ESC/EAS dyslipidaemia focused update, published later, added rows for lipid-lowering during the index ACS admission.^[3] Its table says it complements the 2019 ESC/EAS table and does not replace it.^[3]

• ESC/EAS 2025: intensification of lipid-lowering therapy during the index ACS hospitalisation is recommended for patients who were on any lipid-lowering therapy before admission, in order to further lower LDL-C levels (Class I, Level C).^[3]
• ESC/EAS 2025: initiating combination therapy with high-intensity statin plus ezetimibe during index hospitalisation for ACS should be considered in patients who were treatment-naïve and are not expected to achieve the LDL-C goal with statin therapy alone (Class IIa, Level B).^[3]

Why push combination therapy early?^[3] With the 2019 stepwise approach, optimal LDL-C-lowering therapy can take up to 12 weeks even in an ideal case (ESC/EAS 2025).^[3] SWEDEHEART registry data reported the lowest risk with early and sustained LDL-C lowering to goal after MI.^[3] A stepwise approach after MI might therefore delay goal attainment compared with early intensification.^[3] The Task Force proposes early, intensive LDL-C lowering to be considered in all patients with ACS.^[3] That means immediate initiation of statin therapy, with combination treatment with one or more classes of non-statin therapy with proven cardiovascular benefit as needed, depending on each patient’s lipid-lowering therapy before the ACS event.^[3]

Two more ESC 2023 points sit in its text.^[1] PCSK9 inhibitor treatment should be initiated in hospital if LDL-C was above goal despite statin and ezetimibe before admission.^[1] Icosapent ethyl 2 g twice daily can be used with a statin in ACS with triglycerides of 1.5–5.6 mmol/L (135–499 mg/dL) despite statin.^[1]

ACC/AHA 2025: LDL-C thresholds for adding non-statin therapy

Rows 1, 2 and 4 carry markers showing they were modified or adapted from the 2023 chronic coronary disease guideline.^[2] ACC/AHA 2025 adds that tolerated high-intensity statin therapy should not be de-escalated during follow-up.^[2]

ACC/AHA 2025 Table 11: non-statin options when not at LDL-C goal on maximally tolerated statin (CVD, cardiovascular disease)

^[2]

Ezetimibe lowers LDL-C more with a statin (about 25%) than alone (15%–20%) (Table 11 footnote).^[2] Bempedoic acid with simvastatin above 20 mg or pravastatin above 40 mg is not recommended, because statin muscle adverse effects rise.^[2] Table 12 classes atorvastatin 40–80 mg and rosuvastatin 20–40 mg as high intensity, expected to lower LDL-C by 50% or more.^[2]

For complete or partial statin intolerance, ACC/AHA 2025 says currently available options include ezetimibe, PCSK9 monoclonal antibodies, inclisiran and bempedoic acid.^[2] It notes that ezetimibe and PCSK9 inhibitors are safe and well tolerated and improve lipid parameters in statin-intolerant patients, but outcome studies using these two as monotherapy or in combination in statin-intolerant patients are not available.^[2] Bempedoic acid was compared with placebo in statin-intolerant patients with or at high risk for ASCVD in the CLEAR Outcomes trial, which excluded ACS within 90 days before randomisation; MACE was reduced by 13% (ACC/AHA 2025).^[2] In people with ACS and initial or partial statin intolerance, NHFA/CSANZ 2025 says to consider a different statin, dose or dosing frequency to achieve person-specific therapeutic objectives (weak recommendation, low certainty).^[5]

United States lipid guideline 2026

Two of the secondary ASCVD prevention entries in the What Is New table of the 2026 ACC/AHA dyslipidemia guideline are shown here (selected entries).^[6] The table, it says, is not a comprehensive list of all updates, and some of its recommendations have corresponding footnotes not captured in the table; the class labels below are as listed in that table.^[6]

• Revised (listed as COR 1): in adults with clinical ASCVD who are not at very high risk, high-intensity statin therapy should be initiated to achieve a 50% or greater reduction in LDL-C and a goal of LDL-C below 70 mg/dL (1.8 mmol/L) and non-HDL-C below 100 mg/dL, to reduce the risk of recurrent ASCVD events.^[6]
• New (listed as COR 2a): in adults with clinical ASCVD at very high risk on maximally tolerated statin therapy, ezetimibe and/or a PCSK9 monoclonal antibody should be added, selected by the degree of LDL-C lowering needed and patient preference, to achieve a goal of LDL-C below 55 mg/dL (1.4 mmol/L) and non-HDL-C below 85 mg/dL (2.2 mmol/L) and to reduce the risk of ASCVD events.^[6]

Management: blood pressure, beta-blockers and renin–angiotensin–aldosterone system (RAAS) inhibitors

Blood pressure, nitrates and calcium channel blockers

ESC 2023 Figure 17 targets systolic BP below 130 mmHg and diastolic BP below 80 mmHg, if tolerated.^[1] For patients aged 70 years or more, the systolic target is below 140 mmHg and down to 130 mmHg if tolerated.^[1] Oral nitrates gave no survival benefit after MI in ISIS-4, so ESC 2023 restricts them to residual angina.^[1] Calcium channel blockers showed no prognostic benefit in a systematic review of 28 trials (ESC 2023).^[1] They can be considered for residual angina and for BP control.^[1]

Beta-blockers: the live controversy

• ESC 2023: beta-blockers are recommended in ACS patients with LVEF 40% or less regardless of HF symptoms (Class I, Level A).^[1]
• ESC 2023: routine beta-blockers for all ACS patients regardless of LVEF should be considered (Class IIa, Level B).^[1]
• ACC/AHA 2025: in patients with ACS without contraindications, early (within 24 hours) initiation of oral beta-blocker therapy is recommended to reduce risk of reinfarction and ventricular arrhythmias (COR 1, LOE A).^[2]
• NHFA/CSANZ 2025: in people with ACS and left ventricular (LV) impairment, beta-blockers are recommended (consensus).^[5]
• NHFA/CSANZ 2025: in people with ACS and preserved LV systolic function who have undergone coronary revascularisation and are receiving optimal medical therapy, consider withholding beta-blockers (weak recommendation, moderate certainty).^[5]

ESC 2023 explains its weaker second row.^[1] Evidence after uncomplicated ACS with LVEF above 40% is less well established.^[1] Except CAPRICORN, which recruited only LVEF 40% or less, the large maintenance trials were from the pre-reperfusion era.^[1] Pooled data showed that post-MI beta-blocker therapy reduced the risk of death by more than 20%, but those trials mostly enrolled patients with STEMI, so the evidence for benefit in NSTEMI is less robust.^[1]

ACC/AHA 2025 calls benefit well established with LVEF below 40% and stabilised HF, including after MI.^[2] It says the optimal duration remains unclear with preserved LVEF.^[2] A randomised trial did not confirm long-term benefit after discharge in lower-risk, revascularised patients with preserved LV function.^[2]

In 2023, ESC listed four large European trials of beta-blocker versus control in ACS without reduced LVEF as ongoing.^[1] They were REBOOT-CNIC, REDUCE-SWEDEHEART, BETAMI and DANBLOCK.^[1][4][9] It also listed two ongoing trials of beta-blocker withdrawal after 6–12 months following uncomplicated ACS in patients with preserved LVEF: AβYSS and SMART-DECISION.^[1][8] Several have since reported.^{[7][9][10][8]} REDUCE-AMI carries NCT03278509, the registration ESC 2023 gives for REDUCE-SWEDEHEART.^[1][7] AβYSS carries NCT03498066 in both sources.^[1][8]

^{[7] [1] [9] [1] [4] [10] [8] [1]}

A 2025 individual patient data meta-analysis of four randomised trials assessed long-term oral beta-blocker therapy after a recent MI (randomisation within 14 days) in patients with mildly reduced LVEF (40%–49%) and no history or signs of HF.^[11] It pooled 1885 patients from REBOOT (979), BETAMI (422), DANBLOCK (430) and CAPITAL-RCT (54).^[11][4][9] Of these, 991 were assigned beta-blockers and 894 control.^[11] The primary composite of all-cause death, new MI or HF occurred at 32.6 vs 43.0 per 1000 patient-years.^[11] That was 106 vs 129 patients (hazard ratio 0.75; 95% CI 0.58 to 0.97; p = 0.031).^[11] The authors interpret beta-blockers as associated with a reduction in that composite in this subgroup.^[11]

The NHFA/CSANZ 2025 summary says that with preserved LV function after revascularisation on optimal therapy, beta-blockers may be withheld.^[5] Its reason: evidence shows no reduction in death, MI or other cardiovascular events beyond 12 months.^[5] The 2026 ESC cardiac rehabilitation guideline cites a recent meta-analysis with a similar message.^[4] That meta-analysis suggests no reduction in mortality, recurrent MI or HF with beta-blockers after recent MI with preserved LVEF and no other indication.^[4]

RAAS inhibitors

ACC/AHA 2025 frames ACE inhibitors and angiotensin receptor blockers by risk.^[2]

• ACC/AHA 2025: in high-risk patients with ACS (LVEF 40% or less, hypertension, diabetes mellitus, or STEMI with anterior location), an oral ACE inhibitor or an angiotensin receptor blocker is indicated to reduce all-cause death and MACE (COR 1, LOE A).^[2]
• ACC/AHA 2025: in patients with ACS and LVEF 40% or less, and with HF symptoms and/or diabetes mellitus, a mineralocorticoid receptor antagonist is indicated to reduce all-cause death and MACE (COR 1, LOE B-R).^[2]
• ACC/AHA 2025: in patients with ACS who are not considered high risk, an oral ACE inhibitor or an angiotensin receptor blocker is reasonable to reduce MACE (COR 2a, LOE A).^[2]
• NHFA/CSANZ 2025: in people with ACS and heart failure symptoms, LVEF 40% or less, diabetes, hypertension and/or chronic kidney disease, initiate and continue ACE inhibitors, or angiotensin receptor blockers if ACE inhibitors are not tolerated (strong recommendation, high certainty).^[5]
• NHFA/CSANZ 2025: in people with ACS and LVEF 40% or less and heart failure with or without diabetes, initiate and continue mineralocorticoid receptor antagonists (strong recommendation, high certainty).^[5]

ACC/AHA 2025 says the mineralocorticoid receptor antagonist should be given without advanced CKD, hyperkalaemia or other contraindication.^[2] EPHESUS excluded serum creatinine above 2.5 mg/dL or potassium above 5.0 mmol/L.^[2] ACC/AHA 2025 says starting an ACE inhibitor and an angiotensin receptor blocker together in acute MI should be avoided, because it increases adverse events without added benefit compared with either drug alone.^[2]

Sacubitril-valsartan divides the bodies.^[1][2][5] PARADISE-MI enrolled recent ACS (1–7 days) with HF and/or LVEF 40% or less (ESC 2023).^[1] It found no significantly lower cardiovascular death or incident HF than with ramipril.^[1] ACC/AHA 2025 notes that hypotensive events were more common with sacubitril-valsartan, with no other safety concerns observed.^[2] It says that if sacubitril-valsartan is planned for HF with reduced ejection fraction, starting it instead of an ACE inhibitor or angiotensin receptor blocker early after MI appears safe.^[2] NHFA/CSANZ 2025 says that in people with ACS an angiotensin receptor–neprilysin inhibitor is not recommended (strong recommendation, high certainty).^[5]

Management: diabetes drugs, colchicine and vaccination

SGLT2 inhibitors and GLP-1 receptor agonists

ESC 2023 recommends basing long-term glucose-lowering choice on comorbidities including HF, CKD and obesity (Class I, Level A).^[1] The reduction in new ACS, HF and renal events with SGLT2 inhibitors or GLP-1 receptor agonists is independent of baseline HbA1c, it says.^[1]

• ESC 2023: in type 2 diabetes with established ASCVD, three SGLT2 inhibitor trials showed significant cardiovascular benefit; in a meta-analysis MACE fell by 11%, with no clear effect on stroke or MI, and benefit was seen only with established ASCVD.^[1]
• ESC 2023: in a meta-analysis of seven GLP-1 receptor agonist trials (56 004 patients with type 2 diabetes), use was associated with lower MACE, cardiovascular death, all-cause mortality, MI and stroke.^[1]
• ACC/AHA 2025: in patients without diabetes or HF who had acute MI with impaired LV systolic function, dapagliflozin was not shown to reduce cardiovascular death or HF hospitalisation; in patients without prior HF hospitalised with acute MI and impaired LV systolic function, empagliflozin did not significantly reduce all-cause death or first HF hospitalisation, although it did reduce HF hospitalisations.^[2]
• ACC/AHA 2025: an SGLT2 inhibitor does not need to be deferred in patients with an indication for its use at discharge; semaglutide has been shown to reduce the risk of MACE in overweight or obese patients with stable ASCVD but has not been studied early after ACS.^[2]
• ESC 2026 cardiac rehabilitation guideline: a GLP-1 receptor agonist in addition to lifestyle measures should be considered with a BMI of 27 kg/m² or more (plus high cardiovascular risk or established ASCVD) or obesity, to reduce body weight, MACE and all-cause mortality (Class IIa, Level A).^[4]
• ACC/AHA 2025 safety notes: SGLT2 inhibitors may increase urinary tract infection, genital mycotic infection, hypovolaemia and acute kidney injury; because of perioperative ketoacidosis risk, canagliflozin, dapagliflozin and empagliflozin should be stopped 3 days or more, and ertugliflozin 4 days or more, before scheduled surgery, including CABG.^[2]

^{[14] [15]}

Colchicine

^{[1] [2] [5] [13] [12]}

Other colchicine data come from the guideline texts.^[1][2]

• LoDoCo2 (ESC 2023 description): 5522 patients with chronic coronary syndromes (84% with prior ACS) randomised to colchicine 0.5 mg daily or placebo; the primary composite was significantly lower with colchicine, but non-cardiovascular death was higher.^[1]
• COPS (ACC/AHA 2025 description): colchicine vs placebo started during the index ACS admission; the primary end point was numerically but not significantly lower (P = 0.09), and more deaths occurred with colchicine (8 vs 1; P = 0.017), due to more non-cardiovascular deaths.^[2]
• Meta-analysis (ACC/AHA 2025 description): in coronary artery disease, no difference in all-cause death with colchicine versus placebo, but a non-significant trend towards more non-cardiovascular death that requires further study.^[2]

Vaccination

• ESC 2023: influenza vaccination is recommended for all ACS patients (Class I, Level A); given early after MI or in high-risk coronary artery disease, it has resulted in lower all-cause and cardiovascular death at 12 months.^[1]
• ACC/AHA 2025: in patients with ACS without a contraindication, annual influenza vaccination is recommended to reduce the risk of death and MACE (COR 1, LOE A).^[2]
• ACC/AHA 2025: randomised trial data are lacking to support routinely giving other vaccines at the time of ACS hospitalisation, so regular immunisation schedules per US Centers for Disease Control and Prevention recommendations are supported for all patients in the absence of contraindication.^[2]
• NHFA/CSANZ 2025: vaccinations for influenza and other respiratory pathogens are recommended (consensus); the summary says people with ACS should receive recommended vaccinations, including influenza, pneumococcal, respiratory syncytial virus (for those aged 60 years or more) and COVID-19.^[5]

Management: cardiac rehabilitation, lifestyle, adherence and mental health

Cardiac rehabilitation

ESC 2023 says secondary prevention is most effectively provided through CR.^[1] CR should start as early as possible after the ACS event.^[1] It may be inpatient or outpatient, depending on age, frailty, risk stratification and comorbidities.^[1] Its core components include those listed below.^[1]

• ESC 2023 says the core components of CR include patient assessment; management and control of cardiovascular risk factors; physical activity counselling; prescription of exercise training; dietary advice; tobacco counselling; patient education; psychosocial management; vocational support.^[1]

ESC 2026 strongly recommends exercise training as a key component of CR programmes.^[4]

• ESC 2026: exercise training, as part of CR, is recommended after ACS or with chronic coronary syndromes to reduce cardiovascular mortality, MI and all-cause hospitalisation (Class I, Level A).^[4]
• ESC 2026: resistance training in addition to endurance training during CR is recommended after ACS or with chronic coronary syndromes to achieve greater improvements in physical functioning (VO2 peak) (Class I, Level B1).^[4]
• ESC 2026: early exercise training should be considered in patients recovering from an acute MI to improve LV remodelling (Class IIa, Level B2).^[4]
• ESC 2026: as part of CR, high-intensity interval training may be considered a more effective or time-efficient alternative to moderate-intensity continuous endurance training after ACS or with chronic coronary syndromes, to improve physical functioning (VO2 peak) (Class IIb, Level B1).^[4]

ESC 2026 describes the growing use of telemedicine and digital technologies to enhance or enable CR delivery.^[4] ESC 2023 says telerehabilitation can support or even partially replace centre-based CR.^[1] Few data are available on its effect on recurrent events.^[1] ESC 2026 reports comparable safety for supervised home-based and centre-based CR, given appropriate selection, education and remote monitoring.^[4] The NHFA/CSANZ 2025 summary calls telehealth an acceptable alternative in regional and remote areas.^[5]

Lifestyle and smoking

ESC 2023 recommends a healthy lifestyle after ACS (Class I, Level B).^[1] Its row includes stopping all tobacco smoking, a healthy Mediterranean-style diet, alcohol restriction, regular aerobic and resistance exercise, and less sedentary time.^[1] Alcohol should be restricted to a maximum of 100 g per week, the same limit for men and women.^[1] Daily physical activity does not replace exercise-based CR.^[1]

Tobacco abstinence is associated with 30%–40% less re-infarction and 35%–45% less death after ACS (ESC 2023).^[1] ESC 2023 calls varenicline the most effective medical treatment for cessation and safe in ACS.^[1]

• ESC 2023: in smokers, offering follow-up support, nicotine replacement therapy, varenicline or bupropion, individually or in combination, should be considered (Class IIa, Level A).^[1]
• ESC 2026: pharmacotherapy, including nicotine-replacement therapy, varenicline, bupropion or cytisine, is recommended for patients who smoke and are participating in CR to enhance smoking cessation rates (Class I, Level A).^[4]
• NHFA/CSANZ 2025: for all people with ACS who smoke, advise to stop and refer for behavioural intervention (such as cognitive behaviour therapy or a cessation counselling program), combined with pharmacotherapy where appropriate (nicotine replacement therapies, varenicline and bupropion, individually or in combination) (strong recommendation, moderate certainty).^[5]

E-cigarettes divide the ESC documents.^[1][4] ESC 2023 finds evidence on cessation insufficient and urges caution.^[1] It says current evidence suggests e-cigarettes are harmful to cardiovascular health by increasing arterial stiffness, heart rate and blood pressure, and by causing endothelial dysfunction.^[1] ESC 2026 says e-cigarettes may be considered as an aid to quit tobacco smoking (Class IIb, Level C).^[4] It advises limiting their use and avoiding dual use with cigarettes, because long-term effects are unknown.^[4]

Adherence and the polypill

ESC 2023 says a polypill should be considered as an option to improve adherence and outcomes in secondary prevention after ACS (Class IIa, Level B).^[1] NHFA/CSANZ 2025 says to implement strategies to optimise adherence to preventive medicines for all people with ACS (consensus).^[5] Its examples include discharge prescribing, person-centred medicines education, daily reminders and fixed combination medicines.^[5] Non-adherence generally increases over time (ESC 2023).^[1]

^[16]

Mental health

ESC 2023 says psychological and pharmacological interventions should be considered for depression, anxiety and stress after ACS.^[1] The NHFA/CSANZ 2025 guideline summary recommends screening for depression and other mental health conditions with validated tools and referral for mental health support, because mental health conditions are common after ACS.^[5]

• ESC 2026: cognitive behaviour therapy is recommended for patients with coronary artery disease, HF and ICD recipients to improve mental functioning (depression, anxiety, quality of life) and reduce cardiovascular risk (Class I, Level B1).^[4]
• ESC 2026: antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) should be considered in coronary heart disease with moderate-to-severe major depression to improve depression symptoms (Class IIa, Level B2).^[4]

Specific scenarios and special populations

Older and frail adults

Older age is associated with frailty, multimorbidity and a greater risk of both ischaemic and bleeding events in ACS (ESC 2023).^[1]

• ESC 2023 recommends applying the same diagnostic and treatment strategies in older patients as in younger patients (Class I, Level B).^[1]
• ESC 2023 recommends adapting the choice and dosage of antithrombotic agents and of secondary prevention medications to renal function, co-medications, comorbidities, frailty, cognitive function and specific contraindications (Class I, Level B).^[1]
• ESC 2023: for frail older patients with comorbidities, a holistic approach is recommended to individualise interventional and pharmacological treatments after careful evaluation of risks and benefits (Class I, Level B).^[1]

Chronic kidney disease

ESC 2023 recommends the same diagnostic and therapeutic strategies in CKD as with normal kidney function, noting that dose adjustment may be necessary (Class I, Level C).^[1] For long-term treatment, it refers to the 2021 ESC prevention guideline.^[1]

Diabetes

In diabetes, acute treatment and post-ACS risk factor management are both poorer (ESC 2023).^[1] Coronary disease also tends to be more advanced at diagnosis.^[1] These factors likely contribute to worse long-term prognosis, particularly with insulin treatment.^[1] Diabetes diagnosed during the ACS admission should be confirmed later, because ACS itself may cause catecholamine-induced hyperglycaemia.^[1]

Active cancer

Active cancer diagnosed in the past 12 months counts as HBR under ARC-HBR (ESC 2023).^[1] Because these patients are considered HBR, ESC 2023 names clopidogrel as the preferred P2Y12 inhibitor for ACS patients with active cancer.^[1] It says potential drug–drug interactions with cancer therapies should be checked when using ticagrelor or clopidogrel, since some pharmacokinetic interactions may occur.^[1]

Women

Women often receive less guideline-recommended cardiovascular therapy and face more barriers to optimal care than men (ESC 2026).^[4] CR referral rates are low especially for women (ACC/AHA 2025).^[2]

Complications and pitfalls

• Statin de-escalation: ACC/AHA 2025 says high-intensity statin therapy should not be de-escalated during follow-up in patients who are tolerating it.^[2]
• Bempedoic acid interaction: co-administration with simvastatin above 20 mg or pravastatin above 40 mg is not recommended (ACC/AHA 2025).^[2]
• Dual RAAS blockade: concomitant initiation of an ACE inhibitor and an angiotensin receptor blocker in acute MI should be avoided (ACC/AHA 2025).^[2]
• Relapse after CR: many patients adopt healthier lifestyles during CR but relapse to pre-morbid habits when they return to everyday life (ESC 2023).^[1]
• Smoking relapse: many patients continue or resume smoking after ACS, particularly those with depression and environmental exposures (ESC 2023).^[1]
• Weight gain after quitting: an average gain of 5 kg can be expected, but the cardiovascular risk of continued smoking outweighs the risk of gaining weight (ESC 2023).^[1]
• Colchicine safety: pneumonia was more frequent with colchicine in COLCOT, and non-cardiovascular death was higher with colchicine in LoDoCo2 (ESC 2023).^[1][13]

Prognosis and follow-up

ASCVD event rates are substantially higher after recent ACS than in chronic coronary disease: 1-year rates of cardiovascular death, MI and ischaemic stroke are estimated at 10% to 15% after an ACS hospitalisation (ACC/AHA 2025).^[2] About 1 in 5 patients with ACS are readmitted within 30 days of discharge (ACC/AHA 2025).^[2] Cardiorespiratory fitness strongly predicts prognosis, in the general population and after ACS (ESC 2023).^[1] ESC 2026 recommends using CR as a framework to optimise guideline-directed pharmacotherapies in all patients with a CR indication, to improve health outcomes (Class I, Level C).^[4]

In the sources, follow-up includes these tasks.^[1]

• Recheck lipids after each treatment change: ESC 2023 says lipid levels should be re-evaluated 4–6 weeks after each treatment or dose adjustment; ACC/AHA 2025 recommends a fasting lipid panel 4 to 8 weeks after initiation or dose adjustment of lipid-lowering therapy to assess response or adherence (COR 1, LOE C-LD).^[1][2]
• Reassess LVEF: ESC 2023 recommends repeat LVEF evaluation 6–12 weeks after ACS (after complete revascularisation and optimal medical therapy) when the pre-discharge LVEF was 40% or less, to assess the potential need for a primary prevention ICD (Class I, Level C).^[1]
• Arrange an outpatient review to manage comorbidities and discuss patient goals and preferences (ESC 2023 Figure 17).^[1]

Evidence, guidelines and regional differences

The core sources are the ESC 2023, ACC/AHA 2025 and NHFA/CSANZ 2025 ACS guidelines.^[1][2][5] Newer specialist documents cover lipids (ESC/EAS 2025 focused update; ACC/AHA 2026 dyslipidemia) and rehabilitation (ESC 2026).^[3][6][4] ESC/EAS 2025 says its new rows add to the 2019 guideline and its changed rows substitute for the 2019 ones.^[3]

Selected rows compared across three guidelines (each cell restates that body’s own row and population)

^{[1] [2] [5] [3]}

Exam pearls

References17ShowHide

1. [1]Byrne RA, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J, 2023.PMID 37622654
2. [2]Rao SV, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2025.PMID 40013746
3. [3]Mach F, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J, 2025.PMID 40878289
4. [4]Bäck M, et al. 2026 ESC Guidelines on cardiac rehabilitation. Eur Heart J, 2026.PMID 42661418
5. [5]Brieger DB, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian Clinical Guideline for Diagnosing and Managing Acute Coronary Syndromes 2025. Med J Aust, 2026.PMID 41693087
6. [6]Blumenthal RS, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2026.PMID 41824552
7. [7]Yndigegn T, et al. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med, 2024.PMID 38587241
8. [8]Silvain J, et al. Beta-Blocker Interruption or Continuation after Myocardial Infarction. N Engl J Med, 2024.PMID 39213187
9. [9]Ibanez B, et al. Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. N Engl J Med, 2025.PMID 40888702
10. [10]Munkhaugen J, et al. Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. N Engl J Med, 2025.PMID 40888716
11. [11]Rossello X, et al. β blockers after myocardial infarction with mildly reduced ejection fraction: an individual patient data meta-analysis of randomised controlled trials. Lancet, 2025.PMID 40897190
12. [12]Jolly SS, et al. Colchicine in Acute Myocardial Infarction. N Engl J Med, 2025.PMID 39555823
13. [13]Tardif JC, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med, 2019.PMID 31733140
14. [14]Butler J, et al. Empagliflozin after Acute Myocardial Infarction. N Engl J Med, 2024.PMID 38587237
15. [15]James S, et al. Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure. NEJM Evid, 2024.PMID 38320489
16. [16]Castellano JM, et al. Polypill Strategy in Secondary Cardiovascular Prevention. N Engl J Med, 2022.PMID 36018037
17. [17]Vrints C, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J, 2024.PMID 39210710