Cardio · ischaemic-heart-disease
Chronic coronary syndrome: antianginal therapy, event prevention and where revascularisation fits
Fellowship-level guide to medical therapy in chronic coronary syndrome under the 2024 ESC and 2023 AHA/ACC chronic coronary guidelines, with the newer 2026 ESC cardiac rehabilitation, 2025 ESC/EAS and 2026 ACC/AHA lipid rows and the NHFA/CSANZ 2025 ACS guideline: antianginal drug choice and combinations, antithrombotic, lipid-lowering, RAAS, SGLT2 inhibitor, GLP-1 receptor agonist and colchicine rows, lifestyle and cardiac rehabilitation, vaccination, adherence, follow-up, and the ISCHEMIA trial beside the revascularisation rows.
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- EECC
- ABIM Cardiovascular Disease Certification
Red flags
- In chronic coronary disease, phosphodiesterase type 5 inhibitors should not be used concomitantly with nitrate medications because of risk for severe hypotension (AHA/ACC 2023, COR 3: Harm)
- ESC 2024: ivabradine combined with a non-dihydropyridine CCB or other strong CYP3A4 inhibitors is not recommended (Class III, Level B)
- ESC 2024: nitrates are not recommended in hypertrophic cardiomyopathy or with co-administration of phosphodiesterase inhibitors (Class III, Level B)
- AHA/ACC 2023: chronic nonsteroidal anti-inflammatory drugs should not be used in chronic coronary disease because of increased cardiovascular and bleeding complications (COR 3: Harm)
- ESC 2024: exercise is contraindicated in patients with refractory or unstable angina
What chronic coronary syndrome means, and the two aims of treatment
ESC 2024 defines CCS as a range of clinical presentations or syndromes arising from structural and/or functional alterations related to chronic diseases of the coronary arteries and/or microcirculation.[1] It says these alterations can lead to transient, reversible myocardial demand versus blood supply mismatch, usually (but not always) provoked by exertion, emotion or other stress.[1] It adds that, although stable for long periods, chronic coronary diseases are frequently progressive and may destabilise at any moment with the development of an ACS.[1]
AHA/ACC 2023 uses the term chronic coronary disease.[2] Its guideline applies in the outpatient setting to patients after an ACS or revascularisation once acute issues have stabilised, patients with LV systolic dysfunction and known or suspected CAD or ischaemic cardiomyopathy, and patients with stable angina or ischaemic equivalents managed medically.[2] It also covers angina with evidence of coronary vasospasm or microvascular angina, and CCD diagnosed solely on a screening study when the treating clinician concludes that coronary disease is present.[2]
Treatment has two jobs.[1] ESC 2024 says the main goals of treating CCS are to improve both quality of life and life expectancy.[1] It lists interventions that reduce the risk of cardiac mortality, non-fatal ischaemic events, progression of epicardial and/or microvascular disease, and symptoms and limitations caused by CCS.[1]
ESC 2024 says there is no evidence that any antianginal medication may improve long-term cardiovascular outcomes, except beta-blockers if administered within 1 year after an acute MI.[1] Event prevention, it says, is based on lowering the risk of coronary artery occlusion and consequent ACS, with antithrombotic, lipid-lowering, anti-RAAS, anti-inflammatory and metabolic-acting agents.[1] This page covers drug treatment, lifestyle, vaccination and follow-up. Diagnosis is on Stable chest pain: the CTCA-first pathway, lipid targets on Dyslipidaemia: LDL-C targets, DAPT and bleeding on DAPT complications: bleeding, switching, surgery, and the first year after ACS on Secondary prevention after ACS.
[1]Antianginal drugs: the ESC 2024 approach
Picture a patient whose angina comes on climbing two flights of stairs. ESC 2024 says antianginal therapy aims to control symptoms while ensuring acceptable tolerability and patient adherence.[1] It says there is no robust evidence from direct comparisons that some antianginal drugs are more effective than others for improving symptoms.[1] It adds that many patients need a combination of anti-ischaemic drugs, and that it remains unclear whether upfront combination therapy with two drugs is preferable to monotherapy.[1]
ESC 2024 says the current empirical paradigm has consisted of a hierarchical, stepwise approach with first-line drugs (beta-blockers, CCBs) and second-line drugs (long-acting nitrates, nicorandil, ranolazine, ivabradine, trimetazidine).[1] Its task force instead reinforces tailoring therapy to the haemodynamic profile (BP, heart rate), comorbidities (particularly heart failure), interacting medications and preferences.[1] It also weighs the pathophysiological basis of ischaemia in each patient and local drug availability.[1]
In practice ESC 2024 says that, for many patients with CCS, initial drug therapy should include a beta-blocker and/or a CCB.[1] Other antianginal drugs (long-acting nitrates, ivabradine, nicorandil, ranolazine, trimetazidine) can be added on top of a beta-blocker and/or a CCB, or used as part of initial combination therapy in appropriately selected patients.[1] Regardless of the initial strategy, response should be reassessed and treatment adapted if angina control is inadequate or the drug is poorly tolerated.[1]
ESC 2024: recommendations for antianginal drugs in CCS (Recommendation Table 16)
| Row (ESC 2024, Recommendation Table 16) | Class | Level |
|---|---|---|
| Tailor the selection of antianginal drugs to the patient’s characteristics, comorbidities, concomitant medications, treatment tolerability and underlying pathophysiology of angina, also considering local drug availability and cost | I | C |
| Short-acting nitrates for immediate relief of angina | I | B |
| Initial treatment with beta-blockers and/or CCBs to control heart rate and symptoms, for most patients with CCS (footnote c) | I | B |
| If angina is not controlled by initial treatment with a beta-blocker or a CCB alone, the combination of a beta-blocker and a dihydropyridine CCB (DHP-CCB) should be considered, unless contraindicated | IIa | B |
| Long-acting nitrates or ranolazine should be considered as add-on therapy with inadequate symptom control on beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients (footnote d) | IIa | B |
| When long-acting nitrates are prescribed, a nitrate-free or low-nitrate interval should be considered to reduce tolerance | IIa | B |
| Ivabradine should be considered as add-on therapy with LV systolic dysfunction (LVEF <40%) and inadequate symptom control, or as part of initial treatment in properly selected patients | IIa | B |
| Nicorandil or trimetazidine may be considered as add-on therapy with inadequate symptom control on beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients | IIb | B |
| Ivabradine is not recommended as add-on therapy in patients with CCS, LVEF >40% and no clinical heart failure | III | B |
| Ivabradine combined with a non-DHP-CCB or other strong CYP3A4 inhibitors is not recommended | III | B |
| Nitrates are not recommended in hypertrophic cardiomyopathy or with co-administration of phosphodiesterase inhibitors | III | B |
- Footnote c: these drugs may require caution or may be contraindicated in certain patients with low BP (beta-blockers and DHP-CCB), diabetes (beta-blockers), atrioventricular conduction disorders (beta-blockers and non-DHP-CCB) and chronic obstructive pulmonary disease (non-cardioselective beta-blockers).[1]
- Footnote d (consideration for initial therapy): ivabradine, nicorandil, long-acting nitrates, ranolazine or trimetazidine with intolerance or contraindications to beta-blockers and/or CCBs; ranolazine and trimetazidine for microvascular angina; nicorandil or nitrates for coronary artery spasm. The drugs are listed in alphabetical order.[1]
ESC 2024 says the aim of antianginal medication is adequate relief of angina, in part independently of any effect on major adverse cardiovascular events (MACE).[1] Starting with monotherapy and escalating to a combination when relief is inadequate is, in its words, a reasonable approach.[1] It says starting with a beta-blocker can be recommended in many patients, unless there are contraindications or other drugs suit better, for example with low heart rate and/or BP.[1]
If used for angina, ESC 2024 says the aim should be to lower resting heart rate to 55–60 beats per minute.[1] It calls a beta-blocker with a dihydropyridine CCB appropriate for most patients.[1] Other antianginal drugs can be considered when a beta-blocker and/or CCB is contraindicated or poorly tolerated, or angina stays inadequately controlled; in that list ESC 2024 names ivabradine for patients with LV systolic dysfunction.[1]
ESC 2024 Figure 9 (possible combinations of antianginal drugs) marks useful combinations, combinations that are not recommended, possible combinations, and drugs with similar effects.[1] Its legend says drugs with similar effects can be combined in selected indications: HFrEF (ivabradine and beta-blocker), atrial fibrillation (diltiazem/verapamil and beta-blocker) and vasospastic angina (dihydropyridine CCB and nitrates).[1]
[1]Antianginal drugs: the AHA/ACC 2023 rows
AHA/ACC 2023 explains antianginal drugs through two general mechanisms: decreasing myocardial oxygen demand or increasing myocardial arterial blood supply.[2] Beta blockers, non-dihydropyridine CCBs and ivabradine decrease demand, whereas nitrates and dihydropyridine CCBs increase supply through vasodilatory actions.[2] It says ranolazine has a less well-defined mechanism, potentially decreasing calcium overload through inhibition of the late sodium current.[2]
AHA/ACC 2023: recommendations for medical therapy for relief of angina
| Row (AHA/ACC 2023, Medical Therapy for Relief of Angina) | COR | LOE |
|---|---|---|
| In CCD and angina, antianginal therapy with either a beta blocker, CCB or long-acting nitrate is recommended for relief of angina or equivalent symptoms | 1 | B-R |
| If symptomatic after initial treatment, adding a second antianginal agent from a different therapeutic class (beta blockers, CCB, long-acting nitrates) is recommended | 1 | B-R |
| Ranolazine is recommended in patients who remain symptomatic despite beta blockers, CCB or long-acting nitrate therapies | 1 | B-R |
| Sublingual nitroglycerin or nitroglycerin spray is recommended for immediate short-term relief of angina or equivalent symptoms | 1 | B-NR |
| In CCD with normal LV function, adding ivabradine to standard anti-anginal therapy is potentially harmful | 3: Harm | B-R |
- Why beta blockers come first: AHA/ACC 2023 says beta blockers have been considered the first antianginal to use in symptomatic CCD, although the evidence for this prioritisation is not strong.[2]
- Beta blocker versus CCB: it reports a meta-analysis of 72 studies with fewer weekly angina episodes and lower drug discontinuation with beta blockers, and no difference in death or MI between the classes.[2]
- Verapamil and diltiazem: they can further depress LV function and should not be used in CCD with significant LV dysfunction; with a beta blocker they need caution because of synergistic bradycardia and LV dysfunction.[2]
- Ranolazine trials (AHA/ACC 2023): in CARISA, 823 patients with CCD were randomised to placebo or 1 of 2 ranolazine doses, and after 12 weeks ranolazine improved exercise capacity and relieved angina more effectively than placebo.[2]
- ERICA (AHA/ACC 2023): 565 patients with CCD and persistent symptoms despite a maximally tolerated dose of amlodipine were randomised to ranolazine or placebo; after 6 weeks ranolazine gave significantly fewer anginal episodes and less nitroglycerin consumption.[2]
- Short-acting nitrate before exertion: AHA/ACC 2023 says symptoms can be decreased by taking a short-acting nitrate before activity that typically triggers them.[2]
- Possible harm with ivabradine: AHA/ACC 2023 reports a randomised trial of 19,102 patients with CCD, no evidence of heart failure and resting heart rate of at least 70 per minute, given ivabradine or placebo on top of GDMT including standard anti-anginal treatment.[2]
- Same trial: at about 28 months, cardiovascular death or MI was similar overall; in activity-limiting angina it was higher with ivabradine (7.6% versus 6.5%; P=0.02), which AHA/ACC 2023 says suggests possible harm in this setting.[2]
- Realistic expectations: AHA/ACC 2023 says control of symptoms may be achieved by most patients, but full freedom from angina is only achieved in 40% to 50%, depending on anginal frequency at the start of treatment.[2]
ESC 2024
Recommendation Table 16
- Beta-blockers and/or CCBs as initial treatment for most patients (I B)
- Long-acting nitrates or ranolazine as add-on, or initial in selected patients (IIa B)
- Nicorandil or trimetazidine as add-on with inadequate control on beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients (IIb B)
- Ivabradine: add-on with LVEF <40% (IIa B); not recommended with LVEF >40% and no clinical heart failure (III B)
AHA/ACC 2023
Relief of angina
- Beta blocker, CCB or long-acting nitrate for relief of angina or equivalent symptoms (COR 1, B-R)
- Second agent from a different class (beta blockers, CCB, long-acting nitrates) if symptomatic after initial treatment (COR 1, B-R)
- Ranolazine if symptomatic despite beta blockers, CCB or long-acting nitrates (COR 1, B-R)
- Ivabradine added to standard therapy with normal LV function: potentially harmful (COR 3: Harm)
Two contrasts are worth learning. The long-acting nitrate sits beside the beta blocker and CCB in the AHA/ACC 2023 COR 1 relief-of-angina row, whereas ESC 2024 places it as add-on therapy with inadequate control on beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients (Class IIa).[2][1] In AHA/ACC 2023, ranolazine is recommended (COR 1) in patients who remain symptomatic despite treatment with beta blockers, CCB or long-acting nitrate therapies.[2] In ESC 2024 it should be considered (Class IIa) as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or CCBs, or as part of initial treatment in properly selected patients.[1]
When angina stays despite treatment
AHA/ACC 2023 identifies refractory angina by 3 major features: angina uncontrolled despite intensive medical therapy, objective evidence of an ischaemic cause, and no further options for coronary revascularisation.[2] It says no AHA/ACC class 1 recommendations are possible, given the limited evidence.[2]
- AHA/ACC 2023: in CCD with refractory angina and no other treatment options, enhanced external counterpulsation may be considered for relief of symptoms (COR 2b, LOE B-R).[2]
- ESC 2024: with refractory angina leading to poor quality of life and documented or suspected ANOCA/INOCA, invasive coronary functional testing is recommended to define the endotype and treatment, considering patient choices and preferences (Class I, Level B).[1]
- ESC 2024: with debilitating angina and obstructive CAD refractory to optimal medical and revascularisation strategies, a reducer device for coronary sinus constriction may be considered to improve symptoms, in experienced centres (Class IIb, Level B).[1]
- ESC 2024, follow-up: in all patients with recurrent or worsening angina, lifestyle modification, risk-factor management and guideline-directed medical therapy (GDMT) should be intensified before considering further interventions.[1]
Event prevention: antithrombotic therapy
ESC 2024 says the standard antithrombotic treatment for epicardial atherosclerotic CAD is single antiplatelet therapy (SAPT), typically with aspirin.[1] After ACS or PCI, standard treatment is DAPT for 12 months after ACS (with or without PCI) or 6 months after PCI for CCS.[1] It calls low-dose aspirin (75–100 mg once daily) the traditional drug of choice in CCS, with or without prior MI.[1]
ESC 2024 reports an individual-patient data meta-analysis of secondary prevention trials (43 000 patient-years): aspirin reduced non-fatal MI, non-fatal ischaemic stroke or vascular death from 8.2% to 6.7% per year.[1] That equals 15 fewer serious vascular events per 1000 patients treated for 1 year, and ESC 2024 concludes that in secondary prevention the reduction of ischaemic events with aspirin outweighs serious bleeding.[1]
ESC 2024: long-term antithrombotic rows in CCS (Recommendation Table 17, selected rows)
| Row (ESC 2024, Recommendation Table 17, long-term therapy) | Class | Level |
|---|---|---|
| No clear indication for OAC; prior MI or remote PCI: aspirin 75–100 mg daily lifelong after an initial period of DAPT | I | A |
| No clear indication for OAC; prior MI or remote PCI: clopidogrel 75 mg daily as a safe and effective alternative to aspirin monotherapy | I | A |
| No clear indication for OAC; after CABG: aspirin 75–100 mg daily lifelong | I | A |
| No clear indication for OAC; no prior MI or revascularisation but evidence of significant obstructive CAD: aspirin 75–100 mg daily lifelong | I | B |
| No clear indication for OAC: adding a second antithrombotic agent to aspirin for extended long-term secondary prevention should be considered with enhanced ischaemic risk (footnote c) and without high bleeding risk (footnote d); options in Table 8 | IIa | A |
| No clear indication for OAC; CCS or stabilised post-ACS patients after PCI initially on ticagrelor-based DAPT, still at high ischaemic risk and not at high bleeding risk: ticagrelor monotherapy 90 mg b.i.d. may be considered as an alternative to dual or other single antiplatelet therapy | IIb | C |
| Long-term indication for oral anticoagulation (OAC): an AF therapeutic dose of VKA alone or, preferably, DOAC alone (unless contraindicated) lifelong | I | B |
| Proton pump inhibitor with increased gastrointestinal bleeding risk for the duration of combined antithrombotic therapy | I | A |
| Proton pump inhibitor should be considered with a single antithrombotic drug, considering the individual gastrointestinal bleeding risk | IIa | A |
- Footnote c (enhanced ischaemic risk) includes: stenting of left main stem, proximal LAD or last remaining patent artery; suboptimal stent deployment; stent length >60 mm; diabetes; chronic kidney disease (CKD); bifurcation with two stents; chronic total occlusion treatment; previous stent thrombosis on adequate therapy.[1]
- Footnote d: bleeding risk is judged by PRECISE-DAPT or ARC-HBR criteria.[1]
- ESC 2024 Table 8 (options for extended intensified antithrombotic therapy) includes rivaroxaban 2.5 mg b.i.d. (COMPASS) for CAD or symptomatic PAD at high ischaemic risk, and ticagrelor 60/90 mg b.i.d. (PEGASUS-TIMI 54) after MI in patients who tolerated DAPT for 1 year, each in addition to aspirin.[1]
AHA/ACC 2023: long-term antithrombotic rows in CCD (selected)
| Row (AHA/ACC 2023, antiplatelet therapy and oral anticoagulants) | COR | LOE |
|---|---|---|
| CCD with no indication for oral anticoagulation: low-dose aspirin 81 mg (75–100 mg) to reduce atherosclerotic events | 1 | A |
| Previous MI and low bleeding risk: extended DAPT beyond 12 months for up to 3 years may be reasonable to reduce MACE | 2b | A |
| Without recent ACS or a PCI-related indication for DAPT: adding clopidogrel to aspirin is not useful to reduce MACE | 3: No benefit | A |
| Chronic nonsteroidal anti-inflammatory drugs should not be used (increased cardiovascular and bleeding complications) | 3: Harm | B-R |
| No indication for therapeutic DOAC or DAPT, high risk of recurrent ischaemic events, low-to-moderate bleeding risk: adding rivaroxaban 2.5 mg twice daily to aspirin 81 mg daily is reasonable for long-term MACE reduction | 2a | B-R |
| Requiring oral anticoagulation: DOAC monotherapy may be considered if there is no acute indication for concomitant antiplatelet therapy | 2b | C-LD |
| On DAPT: a PPI can be effective in reducing gastrointestinal bleeding risk | 2a | B-R |
In AF with CCD beyond 1 year after revascularisation (or CAD not requiring it) and no history of stent thrombosis, the 2023 ACC/AHA/ACCP/HRS AF guideline recommends OAC monotherapy over OAC plus single antiplatelet therapy to decrease the risk of major bleeding (COR 1, LOE B-R).[8] After an ACS, the NHFA/CSANZ 2025 guideline (Med J Aust 2026 summary, Table 4) says to prescribe a long-term P2Y12 inhibitor over aspirin once a course of DAPT (1–12 months) is complete (strong recommendation, moderate certainty).[6] DAPT duration after stenting, switching and bleeding are covered on DAPT complications: bleeding, switching, surgery.
Event prevention: lipid lowering
ESC 2024: recommendations for lipid-lowering drugs in CCS (Recommendation Table 18)
| Row (ESC 2024, Recommendation Table 18) | Class | Level |
|---|---|---|
| Lipid-lowering treatment with an LDL-C goal of <1.4 mmol/L (55 mg/dL) and a ≥50% reduction in LDL-C versus baseline | I | A |
| A high-intensity statin up to the highest tolerated dose to reach the LDL-C goals, for all patients with CCS | I | A |
| Goal not achieved with the maximum tolerated statin dose: add ezetimibe | I | B |
| Statin intolerant and goal not achieved on ezetimibe: add bempedoic acid | I | B |
| Goal not achieved on a maximum tolerated statin and ezetimibe: add a PCSK9 inhibitor | I | A |
| Goal not achieved on a maximum tolerated statin and ezetimibe: bempedoic acid should be considered | IIa | C |
| Recurrent atherothrombotic event (not necessarily of the same type) on maximally tolerated statin: an LDL-C goal of <1.0 mmol/L (<40 mg/dL) may be considered | IIb | B |
Two newer lipid guidelines among the guidelines checked for this topic carry related rows. The 2025 ESC/EAS focused update on dyslipidaemias recommends non-statin therapies with proven cardiovascular benefit, alone or in combination, for patients unable to take statin therapy (Class I, Level A).[5] It recommends bempedoic acid in patients unable to take statin therapy to achieve the LDL-C goal (Class I, Level B).[5] It says adding bempedoic acid to the maximally tolerated statin, with or without ezetimibe, should be considered at high or very high risk to achieve the goal (Class IIa, Level C).[5] That table complements the 2019 ESC/EAS table and does not replace it.[5] Targets, statin intolerance and the trial basis are on Dyslipidaemia: LDL-C targets.
- ACC/AHA 2026 dyslipidemia (US rows newer than the 2023 CCD lipid rows), not at very high risk: in adults with clinical ASCVD who are not at very high risk, high-intensity statin therapy should be initiated to achieve ≥50% LDL-C reduction and a goal LDL-C <70 mg/dL (1.8 mmol/L) and non-HDL-C <100 mg/dL to reduce the risk of recurrent ASCVD events (COR 1).[4]
- ACC/AHA 2026, adults with clinical ASCVD not at very high risk and on maximally tolerated statin therapy: it is reasonable to add ezetimibe, a PCSK9 mAb or bempedoic acid (selected on the degree of LDL-C lowering needed and patient preference) to achieve a goal LDL-C <55 mg/dL (1.4 mmol/L) and non-HDL-C <85 mg/dL (2.2 mmol/L) and to reduce the risk of ASCVD events (COR 2a).[4]
- ACC/AHA 2026, adults with clinical ASCVD at very high risk: on maximally tolerated statin therapy, ezetimibe and/or a PCSK9 mAb (selected on the degree of LDL-C lowering needed and patient preference) should be added to achieve a goal LDL-C <55 mg/dL (1.4 mmol/L) and non-HDL-C <85 mg/dL (2.2 mmol/L) and to reduce the risk of ASCVD events (listed as COR 2a); adding bempedoic acid to a statin, with or without ezetimibe and/or a PCSK9 mAb, is reasonable to reach the same goal and to reduce the risk of ASCVD events (COR 2a).[4]
- AHA/ACC/ADA/ASN 2026 CKM, stage 4 (narrative; no class or level given): in CKM syndrome with existing ASCVD it says the presence of CKM components such as diabetes and CKD is associated with increased risk of recurrent ASCVD events, and that these patients frequently fall into the very-high-risk ASCVD subgroup and should receive intensive LDL-C lowering to <55 mg/dL using high-intensity statins, ezetimibe and, if needed, adjunctive therapies such as PCSK9 monoclonal antibodies, inclisiran or bempedoic acid.[9]
- For specific LDL-C recommendations the CKM guideline refers to the ACC/AHA 2026 dyslipidemia guideline.[9]
- Who is very high risk (ACC/AHA 2026): multiple major ASCVD events, or 1 major event plus multiple high-risk conditions; it says most patients with clinical ASCVD are likely to be at very high risk.[4]
- NHFA/CSANZ 2025 (people with ACS): an initial LDL-C target <1.4 mmol/L with at least 50% reduction from baseline (consensus); highest tolerated statin started before discharge and continued indefinitely unless contraindicated or completely statin intolerant (strong, high certainty); consider adding ezetimibe if LDL-C stays suboptimal despite statin therapy or with statin intolerance (weak, moderate); give PCSK9 inhibitors if LDL-C stays suboptimal despite maximally tolerated statin and ezetimibe (strong, high).[6]
Event prevention: RAAS blockade, SGLT2 inhibitors, GLP-1 receptor agonists and colchicine
ESC 2024 says ACE inhibitors can reduce mortality, MI, stroke and heart failure in LV dysfunction, previous vascular disease and high-risk diabetes.[1] It reports a meta-analysis of 24 trials and 61 961 patients: in CCS without heart failure, RAAS inhibitors reduced events and death only when compared with placebo and showed no such reduction against active control.[1] For that reason it says ACE inhibitor therapy in CCS without heart failure or high cardiovascular risk is not generally recommended, unless required to meet BP targets.[1]
Event-prevention drugs beyond antithrombotics and statins: ESC 2024 versus US rows
| Drug class | ESC 2024 row | US row (AHA/ACC 2023 CCD unless another guideline is named) |
|---|---|---|
| ACE inhibitor (or ARB) | Recommended with specific comorbidities such as hypertension, diabetes or heart failure (I A); ACE inhibitors should be considered at very high risk of cardiovascular events (IIa A) | Recommended with hypertension, diabetes, LVEF ≤40% or CKD, ARB if ACE inhibitor–intolerant (COR 1, A); may be considered without hypertension, diabetes or CKD and LVEF >40% (COR 2b, B-R) |
| SGLT2 inhibitor | Recommended with proven cardiovascular benefit (footnote c: canagliflozin, dapagliflozin, empagliflozin, sotagliflozin) in type 2 diabetes and CCS to reduce events, independent of HbA1c and other glucose-lowering drugs (I A) | SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit in CCD with type 2 diabetes to reduce MACE (COR 1, A). AHA/ACC/ADA/ASN 2026 CKM guideline, adults with CKM stage 4 with type 2 diabetes and ASCVD: either an SGLT2 inhibitor or a GLP-1–based therapy with proven cardiovascular benefit is recommended to reduce the risk of cardiovascular events and cardiovascular mortality (COR 1, A) |
| GLP-1 receptor agonist | Recommended with proven cardiovascular benefit (footnote d: dulaglutide, efpeglenatide, liraglutide, semaglutide) in type 2 diabetes and CCS (I A); semaglutide should be considered in overweight (BMI ≥27 kg/m²) or obese CCS without diabetes to reduce cardiovascular mortality, MI or stroke (IIa B) | As above for type 2 diabetes (AHA/ACC 2023 and AHA/ACC/ADA/ASN 2026 CKM, each COR 1, A). AHA/ACC/ADA/ASN 2026 CKM guideline, adults with CKM stage 4 with overweight or obesity (BMI ≥27 kg/m²) and ASCVD: a GLP-1–based therapy with proven cardiovascular benefit, in addition to counselling on healthy dietary intake and regular physical activity, is recommended to reduce the risk of cardiovascular events (COR 1, B-R) |
| Colchicine | Low-dose colchicine (0.5 mg daily) should be considered in CCS with atherosclerotic CAD to reduce MI, stroke and need for revascularisation (IIa A) | Colchicine for secondary prevention may be considered to reduce recurrent ASCVD events (COR 2b, B-R) |
Among the guidelines checked for this topic, the 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic (CKM) guideline is newer than AHA/ACC 2023 CCD. It says CKM stage 4 includes individuals with clinical cardiovascular disease (coronary heart disease, heart failure, stroke, peripheral artery disease or atrial fibrillation) overlapping with CKM risk factors.[9] It retires and replaces the 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults.[9] It gives no recommendations on the general prevention and management of blood pressure, chronic coronary disease, dyslipidaemia, heart failure or peripheral artery disease, which are the focus of other AHA/ACC guidelines.[9] For chronic coronary disease, peripheral artery disease and cerebrovascular disease it points to their AHA/ACC guidelines.[9] It says these emphasise antiplatelet agents and high-intensity or maximally tolerated statin therapy as first-line drugs, with additional lipid-lowering therapies considered as indicated for more intensive LDL-C lowering or management of triglycerides (no class or level given).[9] Its stage 4 rows with a COR and LOE for ASCVD with overweight or obesity, or with type 2 diabetes, are below (its economic value statements are not given); MBS is metabolic and bariatric surgery.[9]
AHA/ACC/ADA/ASN 2026 CKM guideline: stage 4 rows for ASCVD with overweight or obesity or with type 2 diabetes
| Row (AHA/ACC/ADA/ASN 2026 CKM guideline, CKM stage 4) | COR | LOE |
|---|---|---|
| Adults with overweight or obesity and ASCVD: an intensive, multicomponent, behavioural lifestyle intervention is recommended to promote weight loss and improvement in CKM risk factors | 1 | A |
| Adults with overweight or obesity (BMI ≥27 kg/m²) and ASCVD: a GLP-1–based therapy with proven cardiovascular benefit, in addition to counselling to promote healthy dietary intake and regular physical activity, is recommended to reduce the risk of cardiovascular events | 1 | B-R |
| Adults with obesity (BMI ≥30 kg/m²) and ASCVD, weight loss goals not reached with lifestyle interventions, with or without maximally tolerated pharmacotherapy: MBS can be beneficial to facilitate a minimum weight loss of 5% to 10% to improve CKM health and to reduce the risk of cardiovascular events | 2a | B-NR |
| Adults with overweight or obesity (BMI ≥27 kg/m²) and ASCVD: naltrexone/bupropion or phentermine-containing agents are potentially harmful as they can increase BP and heart rate | 3: Harm | B-R |
| Adults with type 2 diabetes and ASCVD: a tailored lifestyle modification plan focusing on a heart-healthy dietary pattern and physical activity is recommended to improve glycaemic control, achieve and maintain a healthy weight, and improve other ASCVD risk factors | 1 | A |
| Adults with type 2 diabetes and ASCVD: either an SGLT2 inhibitor or a GLP-1–based therapy with proven cardiovascular benefit is recommended to reduce the risk of cardiovascular events and cardiovascular mortality | 1 | A |
| Adults with type 2 diabetes and ASCVD: a combination of an SGLT2 inhibitor and a GLP-1–based therapy can be beneficial to improve cardiovascular outcomes | 2a | C-LD |
The CKM monitoring rows that cover stage 4 include the following.[9]
- Lipids, glycaemia and BP: in adults in CKM stages 2 and above, it is recommended to assess lipids, glycaemia and BP at least annually to inform the optimal prevention and management of CVD (COR 1, LOE B-NR).[9]
- After starting GLP-1–based therapy for weight loss: hyporesponsiveness for weight loss should be reassessed periodically (within 3 to 6 months), and insufficient weight loss (<5%) should be addressed with dose escalations, switching to another agent with similar CKM syndrome benefits, and/or referral to a weight management specialist to consider additional therapeutic approaches to optimise weight loss (COR 1, LOE B-NR).[9]
- Stage 2 to 4 CKM syndrome and T2D after starting a cardioprotective glucose-lowering agent (SGLT2 inhibitor or GLP-1–based therapy): glycaemic status should be assessed by HbA1c, blood glucose monitoring and/or continuous glucose monitoring metrics every 3 to 6 months, and more frequently in those not meeting glycaemic goals, to guide further glycaemic management (COR 1, LOE A).[9]
- CKM stage 2 to 4 starting a drug that acts on the RAAS (a renin-angiotensin system inhibitor or a mineralocorticoid receptor antagonist): it is reasonable to recalculate eGFR and measure potassium after 2 to 4 weeks to assess tolerance and safety of the medication regimen (COR 2a, LOE B-R).[9]
ESC 2024 reports the semaglutide outcome trial SELECT: in pre-existing cardiovascular disease with overweight or obesity but no diabetes, weekly subcutaneous semaglutide reduced cardiovascular death, MI or stroke (HR 0.80; 95% CI 0.72–0.90).[1] The ESC 2026 cardiac rehabilitation guideline, newer than ESC 2024 CCS, says a GLP-1 receptor agonist in addition to lifestyle measures should be considered (Class IIa, Level A).[3] Its row covers BMI ≥27 kg/m² plus high cardiovascular risk or established ASCVD, or obesity, and aims to reduce body weight, MACE and all-cause mortality.[3] For colchicine, ESC 2024 reports COLCOT: 4745 patients with recent MI (under 30 days) received colchicine 0.5 mg daily or placebo, regardless of C-reactive protein values.[1] Over a median of 2.3 years the composite outcome occurred in 5.5% on colchicine versus 7.1% on placebo (HR 0.77; 95% CI 0.61–0.96).[1]
[2] [1]Beta-blockers for prognosis
ESC 2024 says beta-blockers can relieve angina or improve prognosis in some patients with CCS.[1] It calls the evidence in post-ACS patients with reduced LVEF solid, but notes no large RCTs supporting beta-blockers after uncomplicated ACS with LVEF >40%.[1] Beyond symptom relief, it says their benefit in CAD without prior MI and with normal LVEF is largely unknown without RCT evidence, and long-term duration after MI with preserved LVEF is debated.[1]
- AHA/ACC 2023: in CCD with LVEF ≤40%, with or without previous MI, beta-blocker therapy is recommended to reduce future MACE, including cardiovascular death (COR 1, LOE A).[2]
- AHA/ACC 2023: if a beta blocker was started for previous MI without a history of or current LVEF ≤50%, angina, arrhythmias or uncontrolled hypertension, it may be reasonable to reassess the indication for long-term (>1 year) use (COR 2b, LOE B-NR).[2]
- AHA/ACC 2023: without previous MI or LVEF ≤50%, beta-blocker therapy is not beneficial in reducing MACE in the absence of another primary indication (COR 3: No Benefit, LOE B-NR).[2]
- NHFA/CSANZ 2025 (people with ACS): beta-blockers are recommended with LV impairment (consensus); with preserved LV systolic function after revascularisation and on optimal medical therapy, consider withholding them (weak, moderate certainty).[6]
Lifestyle, cardiac rehabilitation and exercise
ESC 2024 says education on risk factors and symptom management in CCS is associated with better knowledge, self-care and patient empowerment, and may improve health-related quality of life.[1] It warns that awareness of risk factors through education alone might be insufficient to change behaviour.[1]
ESC 2024: cardiovascular risk reduction, lifestyle and exercise in established CCS (Recommendation Table 15)
| Row (ESC 2024, Recommendation Table 15) | Class | Level |
|---|---|---|
| An informed discussion on CVD risk and treatment benefits tailored to individual patient needs | I | C |
| Multidisciplinary behavioural approaches to help patients achieve healthy lifestyles, in addition to appropriate pharmacological management | I | A |
| A multidisciplinary exercise-based programme to improve cardiovascular risk profile and reduce cardiovascular mortality | I | A |
| Aerobic physical activity of at least 150–300 min per week of moderate intensity or 75–150 min per week of vigorous intensity, and reduction in sedentary time | I | B |
| Home-based cardiac rehabilitation and mobile health interventions should be considered to increase long-term adherence to healthy behaviours and to reduce hospitalisations or cardiac events | IIa | B |
ESC 2024 Table 7: practical advice on lifestyle counselling and interventions (selected rows)
| Topic | ESC 2024 Table 7 advice for established CCS (no class or level given) |
|---|---|
| Immunisation | Vaccination against influenza, pneumococcal disease and other widespread infections, e.g. COVID-19 |
| Smoking and substance abuse | Pharmacological and behavioural strategies to assist smoking cessation; avoid e-cigarettes; abstain from substance abuse |
| Obesity and overweight | Obtain and maintain a healthy weight (BMI 18.5–25 kg/m²); reduce weight through recommended energy intake and increased physical activity, and pharmacological/surgical interventions in selected patients |
| Hyperlipidaemia | Ultimate LDL-C goal of <1.4 mmol/L (55 mg/dL) and a ≥50% reduction versus baseline |
| Diabetes | HbA1c <7.0% (53 mmol/mol) |
| Arterial hypertension | Systolic BP 120–129 mmHg, provided the antihypertensive treatment is well tolerated |
| Diet and alcohol | Limit alcohol to <100 g/week; diet high in vegetables, fruit and wholegrains (Mediterranean diet); saturated fat <10% of total calorie intake |
| Physical activity and exercise | 30–60 min moderate activity, >5 days/week; reduce sedentary time and engage in at least light activity throughout the day |
| Sexual activity | Low risk for stable patients not symptomatic at low-to-moderate activity; in males, PDE-5 inhibitors are generally safe but not to be taken with nitrates because of risk of severe hypotension |
| Psychosocial aspects | Avoid psychosocial stress; treat depression and anxiety by psychological or pharmacological interventions |
ESC 2024 reports a 36% risk reduction of premature death in CCS patients who stop smoking compared with those who continue.[1] It says drug support should be considered in all smokers ready to quit; nicotine replacement, bupropion and varenicline are effective and not linked to an increase in MACE.[1] It says e-cigarettes should be discouraged as an alternative to cigarettes, and considered only to aid cessation alongside a formal tobacco cessation programme.[1] ESC 2026 recommends pharmacotherapy, including nicotine replacement, varenicline, bupropion or cytisine, for patients who smoke and are in cardiac rehabilitation (Class I, Level A).[3]
ESC 2024 says exercise is a therapy that should be offered to every CCS patient in secondary prevention.[1] For aerobic training it recommends at least 3 days per week, preferably 6–7, at moderate or moderate-to-high intensity.[1] It suggests resistance training of one to three sets of 8–12 repetitions at least 2 days per week.[1] It says exercise is contraindicated with refractory or unstable angina and other high-risk conditions such as high-grade arrhythmias, decompensated heart failure, severe aortic dilatation or active thrombo-embolic disease.[1]
The 2026 ESC cardiac rehabilitation guideline is newer than ESC 2024 CCS among the guidelines checked for this topic. It recommends cardiac rehabilitation after ACS or with CCS, with or without PCI or CABG, to reduce cardiovascular mortality and MI (Class I, Level A) and all-cause hospitalisation (Class I, Level B1).[3] It says cardiac telerehabilitation or hybrid telerehabilitation should be considered as an alternative to centre-based programmes in acute and chronic coronary syndromes (Class IIa, Level B1).[3] Home-based rehabilitation without digital support may be considered as an alternative to centre-based rehabilitation in non-high-risk patients (Class IIb, Level B1); these rows are newer than the ESC 2024 home-based rehabilitation row.[3][1]
AHA/ACC 2023: lifestyle and rehabilitation rows in CCD (selected)
| Row (AHA/ACC 2023) | COR | LOE |
|---|---|---|
| Diet emphasising vegetables, fruits, legumes, nuts, whole grains and lean protein to reduce CVD events | 1 | B-R |
| Trans fat should be avoided (associated with increased morbidity and mortality) | 3: Harm | B-NR |
| Nonprescription or dietary supplements, including omega-3 fatty acid, vitamins C, D, E, beta-carotene and calcium, are not beneficial to reduce acute CVD events | 3: No Benefit | B-NR |
| Assess tobacco use at every health care visit | 1 | A |
| Advise patients who regularly smoke to quit at every visit | 1 | A |
| In patients who regularly smoke: behavioural interventions combined with pharmacotherapy (bupropion, varenicline, or combination long- and short-acting nicotine replacement therapy) to maximise cessation | 1 | A |
| In patients who regularly smoke: short-term nicotine-containing e-cigarettes may be considered to aid cessation, although risk of sustained use and unknown long-term safety may outweigh the benefits | 2b | B-R |
| If alcohol is consumed, limiting intake (≤1 drink/d for women, ≤2 drinks/d for men) is reasonable | 2a | B-NR |
| Do not advise alcohol for cardiovascular protection | 3: No Benefit | B-NR |
| Exercise regimen without contraindications: ≥150 minutes/week moderate-intensity or ≥75 minutes/week higher-intensity aerobic activity | 1 | A |
| Resistance (strength) training on ≥2 days/week without contraindications | 1 | B-R |
| All patients with CCD and appropriate indications should be referred to cardiac rehabilitation (LOE A after recent MI, PCI or CABG; B-R with stable angina or after heart transplant; C-LD after recent spontaneous coronary artery dissection) | 1 | A / B-R / C-LD |
| Targeted discussions and screening for mental health, with referral | 2a | B-R |
| Phosphodiesterase type 5 inhibitors should not be used with nitrates (risk of severe hypotension) | 3: Harm | B-NR |
After an ACS, NHFA/CSANZ 2025 recommends referral to a multidisciplinary exercise-based cardiac rehabilitation program before discharge (strong, moderate certainty).[6] For smokers it advises stopping, with referral for behavioural intervention combined with pharmacotherapy where appropriate (strong, moderate certainty).[6]
[2] [3] [1]Vaccination
AHA/ACC 2023 says infections such as influenza, pneumococcal pneumonia and COVID-19 contribute to MACE and all-cause death, especially in CCD.[2] It reports meta-analyses and systematic reviews linking influenza vaccination with lower risk of acute MI, cardiovascular death, MACE and all-cause death in CAD or heart failure.[2]
Vaccination rows
| Source | Row | Strength |
|---|---|---|
| AHA/ACC 2023 | Annual influenza vaccination to reduce cardiovascular morbidity, cardiovascular death and all-cause death | COR 1, LOE A |
| AHA/ACC 2023 | COVID-19 vaccination per public health guidelines to reduce COVID-19 complications | COR 1, LOE C-EO |
| AHA/ACC 2023 | Pneumococcal vaccine is reasonable to reduce cardiovascular morbidity and mortality and all-cause death | COR 2a, LOE B-NR |
| ESC 2024 (Table 7) | Vaccination against influenza, pneumococcal disease and other widespread infections, e.g. COVID-19 | No class or level given |
| NHFA/CSANZ 2025 (people with ACS) | Vaccinations for influenza and other respiratory pathogens | Consensus |
The NHFA/CSANZ summary lists influenza, pneumococcal, respiratory syncytial virus (for those aged 60 years or older) and COVID-19 vaccines for people with ACS, who are at increased risk of severe illness from respiratory infections.[6]
Adherence
ESC 2024 reports that about 28% of CCS patients in the ISCHEMIA trial were non-adherent to prescribed medications at baseline.[1]
ESC 2024: recommendations for adherence to medical therapy and lifestyle changes (Recommendation Table 28)
| Row (ESC 2024, Recommendation Table 28) | Class | Level |
|---|---|---|
| Mobile health interventions (e.g. text messages, apps, wearable devices) to improve adherence to healthy lifestyles and medical therapy | I | A |
| Behavioural interventions to improve adherence | I | B |
| Simplifying medication regimens (e.g. fixed-dose drug combinations) to increase adherence to medications | I | B |
| Multiprofessional and family involvement to promote adherence, in addition to patient education and involvement | I | C |
NHFA/CSANZ 2025 advises strategies to optimise adherence to preventive medicines for all people with ACS (consensus).[6]
Where revascularisation fits: ISCHEMIA and the guideline rows
Medical therapy has improved enough to change the question.[1] ESC 2024 says modern medical therapy has significantly improved survival after conservative treatment, making the benefits of early invasive therapy harder to demonstrate.[1] It also says PCI and CABG prevent ischaemia during exercise or emotional stress but do not heal coronary atherosclerosis.[1]
ISCHEMIA (NEJM 2020) randomised 5179 patients with stable coronary disease and moderate or severe ischaemia to an initial invasive strategy plus medical therapy, or to medical therapy alone with angiography if medical therapy failed.[7] Its primary outcome was cardiovascular death, MI, or hospitalisation for unstable angina, heart failure or resuscitated cardiac arrest.[7]
The trial authors concluded that, over a median of 3.2 years, there was no evidence that an initial invasive strategy reduced ischaemic cardiovascular events or death from any cause, and that findings were sensitive to the MI definition used.[7] ESC 2024 reports that patients assigned to the invasive strategy had significantly lower rates of spontaneous MI and greater improvement in angina-related health status.[1] It also reports ISCHEMIA-EXTEND, follow-up to 7 years, with a significant 2.2% absolute decrease in cardiovascular mortality favouring the initial invasive strategy (adjusted HR 0.78; 95% CI 0.63–0.96).[1] ESC 2024 adds that this was offset by a significant 1.2% absolute increase in non-cardiac mortality, without a significant difference in all-cause mortality.[1] Anatomy, functional testing and the choice between PCI and CABG belong with Stable chest pain: the CTCA-first pathway.
Revascularisation rows beside medical therapy (selected)
| Source | Row | Strength |
|---|---|---|
| ESC 2024 (Recommendation Table 22) | Persistent angina or anginal equivalent despite guideline-directed medical treatment: revascularisation of functionally significant obstructive CAD to improve symptoms | Class I, Level A |
| ESC 2024 | LVEF >35%: revascularisation in addition to GDMT for functionally significant left main stem stenosis, to improve survival | Class I, Level A |
| ESC 2024 | LVEF >35%: revascularisation in addition to GDMT for functionally significant three-vessel disease, to improve long-term survival and to reduce long-term cardiovascular mortality and the risk of spontaneous MI | Class I, Level A |
| ESC 2024 | LVEF >35%: revascularisation in addition to GDMT for functionally significant single- or two-vessel disease involving the proximal LAD, to reduce long-term cardiovascular mortality and the risk of spontaneous MI | Class I, Level B |
| ESC 2024 | LVEF ≤35%: choose between revascularisation or medical therapy alone after careful evaluation, preferably by the Heart Team | Class I, Level C |
| AHA/ACC 2023 | Lifestyle-limiting angina despite GDMT with significant stenoses amenable to revascularisation: revascularisation to improve symptoms | COR 1, LOE A |
| AHA/ACC 2023 | Significant left main disease, or multivessel disease with LVEF ≤35%: CABG in addition to medical therapy over medical therapy alone to improve survival | COR 1, LOE B-R |
| AHA/ACC 2023 | Multivessel CAD appropriate for CABG or PCI: revascularisation in addition to GDMT is reasonable to lower spontaneous MI, unplanned urgent revascularisation or cardiac death | COR 2a, LOE B-R |
Follow-up
ESC 2024 says the main goal of follow-up is to judge the risk of new cardiac events and to identify symptoms suggesting CAD progression.[1] It notes that angina resolves in 40% of CCS patients at 1 year, most often without revascularisation or a change in antianginal therapy.[1] Persistent or recurrent angina carries higher risk of cardiovascular death or MI, though that worse prognosis was only seen in patients with a previous MI.[1] Because no clinical studies have tested predefined pathways, it calls long-term follow-up primarily empirical.[1]
ESC 2024 stepwise follow-up of established CCS (Section 6.3.2)
- 1
Step 1
Annual clinical evaluation by a general practitioner or cardiologist: symptoms, medication review, examination, resting 12-lead ECG, and blood tests for lipids, renal function, glycaemic status and full blood count
- 2
Step 2
New or worsening angina or heart failure symptoms, arrhythmias or ECG changes: further cardiac evaluation, especially if symptoms persist despite optimised GDMT
- 3
Step 3
Persistent symptoms at low exercise levels despite optimised GDMT, or unexpectedly reduced LV function: further testing to detect CAD progression and assess event risk
- 4
Step 4
Recurrent or worsening angina: intensify lifestyle, risk-factor management and GDMT before considering further interventions
ESC 2024 says current medical therapy and lifestyle measures can be maintained or optimised for asymptomatic patients.[1] It says routine functional testing is not recommended for asymptomatic patients after PCI, as it has not improved outcomes compared with standard care after 2 years.[1]
Follow-up rows
| Source | Row | Strength |
|---|---|---|
| ESC 2024 (Recommendation Table 29) | Regardless of symptoms, periodic visits (e.g. annual) to a general practitioner or cardiovascular healthcare professional to review risk-factor control and changes in risk status, disease status and comorbidities | Class I, Level C |
| ESC 2024 | Deteriorating LV systolic function not attributable to a reversible cause: reassess CAD status | Class I, Level C |
| ESC 2024 | New or worsening symptoms: risk stratification, preferably with stress imaging | Class I, Level C |
| ESC 2024 | Symptoms refractory to medical treatment or high risk of adverse events: invasive coronary angiography (with FFR/iFR when necessary) for risk stratification and possible revascularisation | Class I, Level C |
| AHA/ACC 2023 | No change in clinical or functional status on optimised GDMT: routine periodic CT coronary angiography or stress testing is not recommended to guide therapy | COR 3: No benefit, LOE B-R |
| AHA/ACC 2023 | No change in status: routine periodic reassessment of LV function is not recommended | COR 3: No benefit, LOE B-R |
| AHA/ACC 2023 | No change in status: routine periodic invasive coronary angiography should not be performed | COR 3: Harm, LOE B-NR |
| AHA/ACC 2023 | Stable CCD after ACS or revascularisation: referral to telehealth and/or community-based lifestyle programmes may be reasonable as an adjunct to usual care | COR 2b, LOE B-R |
AHA/ACC 2023 says patients with CCD should be observed periodically in the outpatient setting, and that follow-up testing should be reserved for a significant change in symptom and/or clinical status.[2]
[2] [1]Special populations
- Older adults (ESC 2024): at 75 years or older, particular attention to drug side effects, intolerance, drug–drug interactions, overdosing and procedural complications is recommended (Class I, Level C).[1]
- Women (ESC 2024): similar guideline-directed cardiovascular preventive therapy is recommended in women and men (Class I, Level C); systemic post-menopausal hormone therapy is not recommended in women with CCS (Class III, Level A).[1]
- HIV (ESC 2024): attention to interactions between antiretroviral treatment and statins is recommended (Class I, Level B).[1]
- Heart failure and LV dysfunction: in ESC 2024 ivabradine should be considered as add-on antianginal therapy with LVEF <40% and inadequate control of symptoms (Class IIa, Level B); AHA/ACC 2023 says verapamil and diltiazem should not be used with significant LV dysfunction, and recommends beta-blockers with LVEF ≤40% (COR 1).[1][2]
- Hypertrophic cardiomyopathy or phosphodiesterase inhibitor use: nitrates are not recommended (ESC 2024, Class III, Level B).[1]
- Chronic kidney disease: The ESC 2026 cardiovascular disease and CKD guideline (PMID 42661426) is not held (version of record unreachable); none of its rows are used.
ANZ practice
No NHFA/CSANZ guideline dedicated to chronic coronary syndromes was found in the PubMed census for this topic. The NHFA/CSANZ 2025 ACS guideline gives recovery and secondary prevention rows for people with ACS.[6] Its summary describes three classifications of guidance: GRADE recommendations (graded strong or weak in Table 4), consensus recommendations and practice points.[6]
NHFA/CSANZ 2025: secondary prevention rows for people with ACS (selected)
| NHFA/CSANZ 2025 row (Med J Aust 2026 summary, Table 4) | Strength | Certainty |
|---|---|---|
| Refer all people with ACS to a multidisciplinary exercise-based cardiac rehabilitation program before discharge | Strong | Moderate |
| Strategies to optimise adherence to preventive medicines | Consensus | — |
| Vaccinations for influenza and other respiratory pathogens | Consensus | — |
| After a completed course of DAPT (1–12 months): long-term P2Y12 inhibitor over aspirin | Strong | Moderate |
| Initial LDL-C target <1.4 mmol/L and at least 50% reduction from baseline | Consensus | — |
| ACE inhibitors (ARB if not tolerated) with heart failure symptoms, LVEF ≤40%, diabetes, hypertension and/or CKD | Strong | High |
| Consider colchicine 0.5 mg daily after discharge, continued long-term unless contraindicated or not tolerated | Weak | Moderate |
| Preserved LV systolic function after revascularisation on optimal medical therapy: consider withholding beta-blockers | Weak | Moderate |
Evidence, guidelines and regional differences
- Guidelines checked for this topic: rows are given from ESC 2024 CCS, AHA/ACC 2023 CCD, the 2026 ESC cardiac rehabilitation guideline, the 2025 ESC/EAS dyslipidaemia focused update, the 2026 ACC/AHA dyslipidemia guideline, the 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic guideline, the 2023 ACC/AHA/ACCP/HRS AF guideline and the NHFA/CSANZ 2025 ACS guideline (Med J Aust summary); no newer ESC or AHA/ACC chronic coronary guideline was found in the PubMed census.
- Also swept for same-month or newer rows: other held guidelines, including the 2024 ESC hypertension, 2025 AHA/ACC high blood pressure and 2026 ESC heart failure guidelines, whose rows are not quoted; the 2023 ESC diabetes guideline is not held as text for this topic.
- The ESC 2026 cardiovascular disease and CKD guideline (PMID 42661426) is not held (version of record unreachable); none of its rows are used.
- Ivabradine: ESC 2024 says it should be considered as add-on antianginal therapy with LVEF <40% and inadequate symptom control, or as part of initial treatment in properly selected patients (IIa B), and does not recommend it as add-on with LVEF >40% and no clinical heart failure (III B); AHA/ACC 2023 calls adding it to standard anti-anginal therapy with normal LV function potentially harmful (3: Harm).[1][2]
- Colchicine: ESC 2024, low-dose 0.5 mg daily in CCS with atherosclerotic CAD, Class IIa, Level A; AHA/ACC 2023 COR 2b; NHFA/CSANZ 2025 weak recommendation after ACS.[1][2][6]
- Aspirin dose: ESC 2024 75–100 mg daily, lifelong after an initial period of DAPT with a prior MI or remote PCI and no clear indication for oral anticoagulation; AHA/ACC 2023 81 mg (75–100 mg) without an indication for oral anticoagulation.[1][2]
- LDL-C goal: ESC 2024 <1.4 mmol/L with ≥50% reduction (I A). ACC/AHA 2026, clinical ASCVD not at very high risk: <70 mg/dL (1.8 mmol/L) with ≥50% LDL-C reduction on high-intensity statin (COR 1), and on maximally tolerated statin therapy adding ezetimibe, a PCSK9 mAb or bempedoic acid to reach <55 mg/dL (1.4 mmol/L) is reasonable (COR 2a); at very high risk: <55 mg/dL (1.4 mmol/L) (COR 2a rows on adding ezetimibe, a PCSK9 mAb or bempedoic acid on maximally tolerated statin therapy).[1][4]
- GLP-1 therapy with overweight or obesity: ESC 2024 semaglutide in overweight (BMI ≥27 kg/m²) or obese CCS without diabetes to reduce cardiovascular mortality, MI or stroke (IIa B); ESC 2026 cardiac rehabilitation GLP-1 receptor agonist in addition to lifestyle measures with BMI ≥27 kg/m² plus high cardiovascular risk or established ASCVD, or obesity, to reduce body weight, MACE and all-cause mortality (IIa A); AHA/ACC/ADA/ASN 2026 CKM: in adults with CKM stage 4 with overweight or obesity (BMI ≥27 kg/m²) and ASCVD, a GLP-1–based therapy with proven cardiovascular benefit, in addition to counselling on healthy dietary intake and regular physical activity, to reduce the risk of cardiovascular events (COR 1, B-R).[1][3][9]
- Cardiac rehabilitation: the 2026 ESC cardiac rehabilitation rows (Class I, Level A for cardiovascular mortality and MI) are newer than the ESC 2024 CCS exercise-programme row.[3][1]
Exam pearls
- ESC 2024 resting heart-rate aim with a beta-blocker used for angina: 55–60 beats per minute.[1]
- ESC 2024 three Class III antianginal rows: ivabradine with LVEF >40% and no clinical heart failure; ivabradine with a non-DHP-CCB or strong CYP3A4 inhibitor; nitrates in hypertrophic cardiomyopathy or with phosphodiesterase inhibitors.[1]
- ESC 2024 footnote d: ranolazine and trimetazidine for microvascular angina; nicorandil or nitrates for coronary artery spasm, as initial-therapy considerations.[1]
- ESC 2024: when long-acting nitrates are prescribed, a nitrate-free or low-nitrate interval should be considered to reduce tolerance (Class IIa, Level B).[1]
- AHA/ACC 2023: adding clopidogrel to aspirin without recent ACS or a PCI-related indication is not useful (3: No benefit), and chronic NSAIDs should not be used (3: Harm).[2]
- AHA/ACC 2023: nonprescription or dietary supplements, including omega-3 fatty acid, vitamins C, D and E, beta-carotene and calcium, are not beneficial to reduce the risk of acute CVD events (3: No Benefit).[2]
- ISCHEMIA: 5179 patients with stable coronary disease and moderate or severe ischaemia; over a median of 3.2 years, no evidence that an initial invasive strategy, compared with an initial conservative strategy, reduced ischaemic cardiovascular events or death from any cause.[7]
References9ShowHide
- [1]Vrints C, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J, 2024.PMID 39210710
- [2]Virani SS, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2023.PMID 37480922
- [3]Bäck M, et al. 2026 ESC Guidelines on cardiac rehabilitation. Eur Heart J, 2026.PMID 42661418
- [4]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
- [5]Mach F, et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J, 2025.PMID 40878289
- [6]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
- [7]Maron DJ, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. N Engl J Med, 2020.PMID 32227755
- [8]Joglar JA, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2024.PMID 38033089
- [9]Ndumele CE, et al. 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2026.PMID 42265997