Clinical Practice Guidelines

Risk estimation: Adopts SCORE2 (age <70) and SCORE2-OP (age ≥70) in place of the original SCORE algorithm for 10-year fatal + non-fatal CVD risk. Risk categories (very high / high / moderate / low) are redefined using SCORE2/SCORE2-OP thresholds. LDL-C treatment goals are unchanged from 2019: <1.4 mmol/L (<55 mg/dL) + ≥50% reduction for very high risk; <1.8 mmol/L (<70 mg/dL) for high risk; <2.6 mmol/L (<100 mg/dL) for moderate risk.

New therapies: Bempedoic acid (Class I for statin-intolerant patients; Class IIa as add-on to maximally tolerated statin ± ezetimibe). Evinacumab (Class IIa for homozygous FH age ≥5 not at goal). Inclisiran outcome trials ongoing (results expected 2026–2027).

ACS — "strike early and strong": Intensification of lipid-lowering during index ACS hospitalization (Class I). Initiate combination statin + ezetimibe during hospitalization for treatment-naïve patients unlikely to reach goal on statin alone (Class IIa).

Lp(a): Levels >50 mg/dL (105 nmol/L) should be considered a CV risk-enhancing factor (Class IIa). Measurement recommended at least once per lifetime. Specific Lp(a)-lowering therapies in trials (RNA-based agents lower Lp(a) by 80–98%).

Hypertriglyceridemia: High-dose icosapent ethyl (2 × 2 g/day) endorsed (Class IIa) for high/very-high risk with elevated triglycerides on statin. Combined EPA/DHA (STRENGTH trial) did not show benefit — recommendation now explicitly specifies purified EPA. Volanesorsen (Class IIa) for familial chylomicronemia syndrome (EMA-approved only).

Special populations: Statin therapy recommended (Class I) for HIV patients ≥40 years in primary prevention regardless of estimated risk (REPRIEVE trial). Statins considered (Class IIa) for cancer patients at high/very high chemotherapy-related CV toxicity risk (STOP-CA trial). Dietary supplements not recommended (Class III) for ASCVD risk reduction.

Treatment goals restored: The 2018 ACC/AHA guideline had moved away from specific LDL-C targets; the 2026 guideline restores them. Very high-risk ASCVD: LDL-C <55 mg/dL, non-HDL-C <85. Not-very-high-risk ASCVD: LDL-C <70, non-HDL-C <100 (optional <55/<85). Subclinical atherosclerosis and diabetes with risk factors: LDL-C <100. CAC ≥1000: treated like very high-risk ASCVD (LDL-C <55).

PREVENT-ASCVD equations replace Pooled Cohort Equations: New risk calculator derived from ~3.3 million US adults. Race-neutral (race/ethnicity deliberately excluded as a variable). Predicts 10-year and 30-year total ASCVD risk. Risk categories recalibrated: low (<3%), borderline (3–<5%), intermediate (5–<10%), high (≥10%). The old PCE overpredicted risk by 40–50%; old PCE ≥5% maps to PREVENT ≥3%.

Lp(a) measurement — universal, COR 1: At least once in all adults. Graded risk: 1.4-fold at 125 nmol/L (50 mg/dL), 2-fold at ~250 nmol/L, ~4-fold at ~430 nmol/L. ~90% genetically determined; statins do not lower it. Actionable step: intensify management of other modifiable risk factors. PCSK9 mAb recommended (COR 1) for ASCVD patients with elevated Lp(a) not at LDL-C goal. Specific Lp(a)-lowering therapies (mRNA, small-molecule inhibitors) still in trials.

ApoB measurement: Recommended for guiding therapy in patients with ASCVD, CKM syndrome, diabetes, or elevated TG. Positioned as a better predictor of ASCVD than LDL-C alone, particularly when LDL-C may be misleadingly "at goal" while atherogenic particle number remains high. Optional apoB goals introduced: <55 mg/dL for very high risk, <70 for not-very-high-risk ASCVD, <90 in diabetes pathway.

CAC scoring — most granular guidance in any guideline: Five tiers with specific LDL-C targets for each: CAC = 0 (reasonable to defer statin); 1–99 and <75th percentile (moderate-intensity statin, LDL-C <100); 100–299 or ≥75th percentile (LDL-C <70); 300–999 (LDL-C <70); ≥1000 (LDL-C <55 — same as very high-risk ASCVD). AI-detected incidental CAC on noncardiac CT: COR 2a for initiating statin. Repeat CAC every 3–7 years when deferred. ~40% of intermediate-risk adults have CAC = 0.

Treatment intensification ladder: High-intensity statin → add ezetimibe → add PCSK9 mAb or bempedoic acid. Combination therapy approach now much more explicit. Bempedoic acid: significant coverage for statin-intolerant patients (CLEAR Outcomes trial). Inclisiran: included in pathways (LDL-C reduction ~50%) but CVOTs pending — ORION 4 expected 2026, VICTORION-2 expected 2027.

Hypertriglyceridemia — tiered approach: Lifestyle management first-line (COR 1). For ASCVD + elevated TG on statin: prioritize LDL-C lowering first. IPE (icosapent ethyl) given COR 2b only — weaker than ESC's Class IIa; guideline notes REDUCE-IT mineral oil placebo controversy and that biomarker subanalysis showed no improvement in atherogenic lipids or inflammatory markers. Olezarsen (apoC-III ASO) COR 1 for FCS with TG ≥1000. Only purified EPA trials showed CV benefit; combined EPA/DHA (STRENGTH) did not.

Special populations: HIV: statin COR 1 for PLHIV aged 40–75 on stable ART (REPRIEVE trial — pitavastatin 35% MACE reduction). Cancer survivors: treat same as general population if life expectancy ≥2 years (COR 1). HFrEF without ischemic ASCVD: Class 3 No Benefit for initiating LLT. Primary prevention with LDL-C <70 and non-HDL-C <100: Class 3 No Benefit for initiating LLT. Statin-attributed muscle symptoms: 8 recommendations — most granular SAMS framework in any guideline; acknowledges the "drucebo effect"; CoQ10 supplementation Class 3 No Benefit.

Full guideline vs focused update: The US 2026 is a complete replacement of the 2018 guideline (~90 clinical pages, retitled from "Blood Cholesterol" to "Dyslipidemia"). The EU 2025 is a focused update of the 2019 ESC/EAS guideline — all 2019 recommendations not explicitly changed remain in effect. The US document is substantially more comprehensive in scope.

Risk assessment tools: US uses PREVENT-ASCVD (derived from 3.3M US adults, race-neutral, predicts total ASCVD events, 10-year and 30-year); EU uses SCORE2/SCORE2-OP (predicts fatal + non-fatal CVD). Both are newer-generation and race-neutral, but calibrated from different populations with different endpoints. PREVENT risk thresholds are lower (≥3% ≈ old PCE ≥5%), which shifts who gets treated.

LDL-C targets — strong convergence: Both target LDL-C <55 mg/dL (1.4 mmol/L) for very high-risk. US adds a second tier: <70 mg/dL for ASCVD "not at very high risk" (with optional <55). EU uses <55 as a flat target for all very high-risk patients (Class I). EU treatment goals are unchanged from 2019; US goals are newly restored after the 2018 guideline had abandoned specific targets.

CAC scoring — major US innovation: The US 2026 guideline provides dramatically more granular CAC guidance than anything ESC has published — five tiers with specific LDL-C targets, AI-detected incidental CAC, repeat testing intervals, and CAC = 0 as a de-risking tool. The EU focused update does not have a comparable CAC framework.

ApoB positioning: Both recommend apoB measurement, but the US integrates it more deeply into treatment algorithms with optional apoB goals at each risk tier (<55, <70, <90 mg/dL). The EU mentions apoB but does not restructure its algorithms around it to the same degree.

Lp(a): Both recommend universal measurement at least once (US: COR 1; EU: Class IIa as risk enhancer). Both acknowledge no approved specific Lp(a)-lowering therapy. US gives COR 1 for adding PCSK9 mAb in ASCVD patients with elevated Lp(a) not at LDL-C goal. The EU position is similar but the 2025 focused update doesn't restructure Lp(a) management as a standalone section.

Icosapent ethyl — divergent confidence: US gives IPE COR 2b (weakest positive recommendation) with explicit caveats about the REDUCE-IT mineral oil placebo controversy and biomarker subanalysis findings. EU gives IPE Class IIa (stronger endorsement). Both specify purified EPA only (not combined EPA/DHA based on STRENGTH).

Bempedoic acid: Both endorse bempedoic acid for statin-intolerant patients. US gives broader coverage across multiple pathways (primary prevention, secondary prevention, SAMS management, diabetes). EU gives Class I for statin-intolerant and Class IIa as add-on.

HIV: Strong convergence — both cite REPRIEVE and recommend statin therapy for PLHIV. US specifies ages 40–75 (COR 1 / B-R); EU gives Class I regardless of estimated risk. US provides a comprehensive statin–ART drug interaction table (Table 22) not paralleled in the EU document.

Inclisiran: Both include inclisiran but flag missing CVOT data. US positions it as COR 2a in the SAMS pathway for ASCVD patients unable to access PCSK9 mAb; EU mentions it with outcome trials pending. Neither gives it a strong standalone recommendation for routine use.

DOI note: The US 2026 guideline was published simultaneously in Circulation (DOI: 10.1161/CIR.0000000000001423) and JACC (DOI: 10.1016/j.jacc.2025.11.016). The Circulation version is the primary source for this review.

EU correction notice: A correction to the EU 2025 focused update was published Feb 7, 2026 (doi: 10.1093/eurheartj/ehaf1036) — should be checked for material changes to recommendations.

Ongoing trials to watch: Two inclisiran CVOTs (ORION 4 expected ~2026; VICTORION-2 expected ~2027). EVOLVE-MI and AMUNDSEN-real testing evolocumab at ACS onset (2026–2027). Multiple Lp(a)-lowering agents in phase III trials (pelacarsen, olpasiran, lepodisiran, muvalaplin, zerlasiran). Two statin primary prevention RCTs in adults >70 are ongoing and may clarify benefit in this age group.

Key nuance — focused update vs full guideline: The EU 2025 is a focused update, not a full replacement of the 2019 ESC/EAS Guidelines; the 2019 base guideline (doi: 10.1093/eurheartj/ehz455) should be read alongside it. The US 2026 is a complete replacement of the 2018 guideline.

US evidence gaps acknowledged: The guideline identifies 9 key unanswered questions, including whether early LLT in low-risk young adults with subclinical atherosclerosis reduces long-term risk, whether pharmacological Lp(a) lowering reduces ASCVD events, how apoB should be incorporated into future trial designs alongside LDL-C, and how serial plaque imaging (CCTA, IVUS) compares with event-driven endpoints as surrogate measures.

Internal inconsistency — CAC = 0 in FH (US 2026): The guideline establishes CAC as its most informative direct measure of coronary disease and uses CAC = 0 as a basis for deferring statin therapy in primary prevention (~40% of intermediate-risk adults have CAC = 0), in older adults (benefits "unlikely to outweigh potential risks"), and in patients with statin-attributed muscle symptoms (deferral supported for up to 5 years). However, in FH patients, using CAC = 0 to defer treatment is rated Class 3: Harm — the strongest possible negative recommendation. This creates an unresolved contradiction: a 60-year-old FH patient with lifelong elevated LDL-C and CAC = 0 has had decades of exposure without producing detectable calcified disease, yet the guideline says deferring treatment in this patient is harmful. No outcome data exist for this specific subgroup (FH + CAC = 0) to support this rating — it is based on expert consensus (Level C-EO). The guideline's own NNT/NND data suggest the risk-benefit calculus in a CAC = 0 population would be unfavorable, since event rates with CAC = 0 are very low regardless of LDL-C level while statin side effects (including new-onset diabetes at NND ≈ 100) remain constant. In effect, the guideline has made the cumulative LDL-C exposure model unfalsifiable by measurement in FH — the test result cannot change the recommendation, which raises the question of why the test would be performed.

New BP classification (simplified to 3 categories): Non-elevated BP (office SBP <120 and DBP <70 mmHg), Elevated BP (120–139 / 70–89 mmHg), and Hypertension (≥140/90 mmHg). The previous grading system (Grade 1/2/3, high-normal, etc.) and 3-stage classification from 2018 are retired.

Hypertension threshold unchanged at 140/90 mmHg — but the guideline now emphasizes that CVD risk from BP is continuous, not binary. The title itself changed from "arterial hypertension" to "elevated blood pressure and hypertension" to reflect this.

Treatment targets (Class I): SBP 120–129 mmHg for most treated adults. DBP 70–79 mmHg (Class IIb). Applies the ALARA principle — "As Low As Reasonably Achievable" — with relaxed targets for age ≥85, moderate-to-severe frailty, symptomatic orthostatic hypotension, or limited life expectancy.

Risk-based treatment for elevated BP: In the elevated BP category (120–139/70–89), drug treatment is recommended for those at sufficiently high CVD risk (established CVD, moderate-to-severe CKD, HMOD, diabetes, FH) or SCORE2/SCORE2-OP ≥10%. For SCORE2 5–<10%, risk modifiers are assessed. Drug treatment is initiated if confirmed BP remains ≥130/80 mmHg after lifestyle measures.

Pharmacotherapy: Upfront low-dose dual combination therapy (Class I) for confirmed hypertension using ACE inhibitor or ARB + CCB or thiazide/thiazide-like diuretic, preferably as single-pill combination. Step up to triple combination if needed. Spironolactone recommended as fourth-line for resistant hypertension (Class IIa). Beta-blockers reserved for compelling indications (post-MI, HF, rate control).

Out-of-office BP measurement: Recommended (Class I) for diagnosis (detecting white-coat and masked hypertension) and for ongoing management/titration. HBPM and ABPM considered complementary.

Screening for primary aldosteronism: Now recommended for all hypertensive adults (Class IIa) — a significant change reflecting growing evidence of underdiagnosis.

Renal denervation: May be considered (Class IIb) for resistant hypertension at experienced centres after shared decision-making. Contraindicated if eGFR <40 (Class III).

Hypertension definition threshold — the biggest divergence: EU defines hypertension at ≥140/90 mmHg; the US 2025 AHA/ACC guideline uses 130/80 mmHg (carried forward from 2017). This means many patients are "hypertensive" in US guidelines but only have "elevated BP" under ESC classification.

Treatment targets converge somewhat: Both now target SBP ~120 mmHg in most adults, though ESC specifies 120–129 mmHg as the target range (with ALARA principle) while US uses <130/80 as a threshold. ESC's approach is arguably more intensive once treatment starts (target lower than the old 2018 ESC target of <130).

Who gets treated: ESC uses a risk-based approach for elevated BP (120–139/70–89), requiring CVD risk assessment before drug initiation. The US approach with the lower 130/80 threshold for defining hypertension leads to more people receiving medication from the outset without requiring formal risk scoring.

Combination therapy: Both favour early combination therapy. ESC gives upfront dual combination a Class I recommendation for confirmed hypertension; US 2025 guideline similarly endorses initial combination therapy.

Pending: Full comparison to be updated after US 2025 AHA/ACC hypertension guideline is reviewed in detail.

Correction notice: A correction was published Apr 7, 2025 (doi: 10.1093/eurheartj/ehaf031) — should be checked for material changes.

Major new trials post-publication: ESPRIT (intensive SBP <120 vs <140 in China, published Lancet 2024) and an intensive BP trial in type 2 diabetes (NEJM, Nov 2024) further support intensive targets — broadly consistent with the ESC 2024 direction.

Emerging therapies mentioned in guideline (awaiting outcome data): Aldosterone synthase inhibitors (baxdrostat, lorundrostat) — significant BP lowering in phase 2 trials. Zilebesiran (RNA interference targeting angiotensinogen) — single dose lowers 24h BP for ~6 months. Aprocitentan (dual endothelin receptor antagonist) — phase 3 data in resistant hypertension. None yet recommended for routine use pending CV outcomes trials.

This is a full guideline replacement (not a focused update) — the entire 2018 ESC/ESH guideline is superseded. Note ESH is no longer a co-author society; the 2024 guideline is ESC-only, endorsed by ESE and ESO.

SGLT2 inhibitors for HFmrEF (Class I, Level A): Dapagliflozin or empagliflozin now recommended for symptomatic HFmrEF (LVEF 41–49%) to reduce HF hospitalization or CV death. Based on EMPEROR-Preserved and DELIVER trials and meta-analysis showing 20% reduction in the composite endpoint. Note: benefit was driven by reduction in HF hospitalizations, not CV death individually.

SGLT2 inhibitors for HFpEF (Class I, Level A): Same recommendation for symptomatic HFpEF (LVEF ≥50%). This is the first Class I disease-modifying therapy for HFpEF — a landmark change, as prior trials with ACE-I, ARB, MRA, and ARNI all failed their primary endpoints in this population.

Acute HF — rapid up-titration (Class I, Level B): Based on STRONG-HF trial. Intensive strategy of initiating and rapidly up-titrating evidence-based therapies (ACE-I/ARB/ARNI, beta-blockers, MRA) before discharge and during frequent follow-up in first 6 weeks post-discharge. Reduced HF rehospitalization by 44% (aRR 0.56). Important caveats: selected population (elevated NT-proBNP with >10% decline), no SGLT2 inhibitors in the protocol (though now recommended alongside).

CKD + T2DM — HF prevention: SGLT2 inhibitors (Class I, Level A) and finerenone (Class I, Level A) both recommended to reduce HF hospitalization risk in patients with T2DM and CKD. Based on DAPA-CKD, EMPA-KIDNEY, FIDELIO-DKD, FIGARO-DKD trials.

Iron deficiency: IV iron supplementation recommended (Class I, Level A) for symptom relief in HFrEF/HFmrEF with iron deficiency. IV ferric carboxymaltose or ferric derisomaltose should be considered (Class IIa, Level A) to reduce HF hospitalizations. Based on IRONMAN, AFFIRM-AHF, and meta-analyses.

Diuretics (no new recommendation): ADVOR (acetazolamide) and CLOROTIC (hydrochlorothiazide add-on) showed improved decongestion but no outcomes benefit — further data needed before guideline endorsement.

Correction notice: A correction was published Jan 1, 2024 (doi: 10.1093/eurheartj/ehad613).

Focused update, not full replacement: All 2021 ESC HF Guidelines recommendations not explicitly changed remain in effect. The base guideline (doi: 10.1093/eurheartj/ehab368) should be read alongside this update.

HFpEF terminology: The Task Force discussed changing "HFpEF" to "HFnEF" (HF with normal EF) but decided to defer this to the next full guideline update.

SGLT2i nuance: Both HFmrEF and HFpEF recommendations note that the composite endpoint benefit was driven by HF hospitalization reduction, with no statistically significant reduction in CV death alone — though a pooled analysis of dapagliflozin data (DAPA-HF + DELIVER) did show reduced CV death across the full EF spectrum.

New AF staging classification: Replaces the duration-only scheme (paroxysmal/persistent/permanent) with a 4-stage continuum — Stage 1: at risk; Stage 2: pre-AF (structural/electrical substrate); Stage 3: AF (3a paroxysmal, 3b persistent, 3c long-standing persistent, 3d successful ablation/no recurrence); Stage 4: permanent AF. Emphasizes AF as a progressive disease requiring different strategies at each stage.

Lifestyle & risk factor modification as a pillar: Elevated to a core management strategy across all stages. Prescriptive recommendations for obesity management (weight loss), physical activity, smoking cessation, alcohol moderation, BP control, and sleep apnea treatment.

Anticoagulation — risk-based approach: Patients with estimated annual stroke risk ≥2% (using CHA₂DS₂-VASc or other validated scores) should receive anticoagulation (Class 1). DOACs preferred over warfarin (Class 1). For patients at intermediate risk, additional stroke risk modifiers (AF burden, sex, BP control) can inform shared decision-making. LAA occlusion devices upgraded to Class 2a for patients with long-term contraindications to anticoagulation.

Catheter ablation — Class 1 as first-line in select patients: Ablation upgraded to Class 1 indication as first-line rhythm control therapy in appropriately selected patients (symptomatic paroxysmal AF, younger, few comorbidities). Also Class 1 for AF with HFrEF. Emphasis on early rhythm control based on EAST-AFNET 4 and other trials showing reduced CV events with early intervention.

Device-detected AF: More prescriptive recommendations considering interaction between episode duration and CHA₂DS₂-VASc score for anticoagulation decisions in subclinical AF detected by implantables/wearables.

AF during medical illness/surgery: New recommendations recognizing risk of recurrent AF after AF discovered during non-cardiac illness or surgical precipitants.

AF classification: US introduces a 4-stage model (disease continuum); EU 2024 introduces AF-CARE pathway (Comorbidity/risk factor management, Avoid stroke, Reduce symptoms, Evaluation). Both move beyond simple duration-based classification but take different organizational approaches.

Stroke risk assessment: US allows flexibility beyond CHA₂DS₂-VASc, endorsing other validated scores and stroke risk modifiers for shared decision-making. EU 2024 also introduced CHA₂DS₂-VA (dropping the sex modifier from scoring, using it as a risk modifier instead). Threshold for anticoagulation is similar (~≥2% annual risk) but scoring mechanics differ.

Catheter ablation: Both give Class 1 for ablation as first-line in selected patients and for AF with HFrEF — a major convergence. Both emphasize early rhythm control.

LAA occlusion: US upgraded to Class 2a; EU 2024 also gives Class 2a for patients with contraindications to long-term anticoagulation — aligned.

DOACs vs VKA: Both strongly prefer DOACs (Class 1). Neither recommends DOACs in moderate-to-severe mitral stenosis or mechanical valves.

Corrections (US): Two corrections published — Dec 28, 2023 (doi: 10.1161/CIR.0000000000001207) and Feb 26, 2024 (Circulation 149(9):e936).

Timing gap: The US guideline (Nov 2023) and EU guideline (Aug 2024) are only 9 months apart — unusual alignment in timing. The EU guideline had access to some additional data.

Pulsed field ablation (PFA): Emerging technology not fully addressed in either guideline. Early data suggest comparable efficacy to radiofrequency/cryoablation with potentially improved safety profile — likely to feature in future updates.

Full guideline replacement: The US 2023 guideline replaces both the 2014 AHA/ACC/HRS guideline and the 2019 focused update entirely.

First unified ACS guideline: Combines STEMI, NSTEMI, and unstable angina into one document for the first time (previously separate 2017 STEMI and 2020 NSTE-ACS guidelines). Reflects view that these are different presentations within the ACS spectrum.

Initial assessment — "Think A.C.S.": A = Abnormal ECG?, C = Clinical context?, S = Stable patient? Working diagnosis → final diagnosis approach emphasizing hs-cTn algorithms (0h/1h or 0h/2h) for rapid rule-in/rule-out of NSTEMI (Class I).

Invasive strategy timing: Immediate invasive approach for STEMI and very high-risk NSTE-ACS. Early invasive strategy (within 24h) should be considered (Class IIa — revised from previous Class I) for NSTE-ACS with high-risk criteria. Intravascular imaging to guide PCI now Class IIa.

Antithrombotic therapy: 12-month DAPT remains the default strategy (Class I). Key new/revised de-escalation options: after 3–6 months event-free DAPT in non-high-ischaemic-risk patients, single antiplatelet therapy (preferably P2Y12 inhibitor) should be considered (Class IIa). P2Y12 inhibitor monotherapy may be considered as an alternative to aspirin for long-term treatment (Class IIb). De-escalation in the first 30 days is not recommended (Class III).

Patients requiring OAC: Withdrawing antiplatelet therapy at 6 months while continuing OAC may be considered (Class IIb).

MINOCA: Dedicated section on MI with non-obstructive coronary arteries, with systematic diagnostic workup recommended including CMR.

Secondary prevention: Early and intensive lipid-lowering emphasized (aligning with ESC dyslipidemia guidance). Cardiac rehabilitation and lifestyle management recommended for all ACS patients.

Patient-centred care: New emphasis throughout — recommending inclusion of patients in decision-making, assessment of individual preferences, use of decision aids, and attention to sex-specific differences in ACS presentation and management.

Guideline timing: EU ACS guideline published Aug 2023; US ACS guideline published Feb 2025 — an 18-month gap. The US guideline had access to substantially more recent evidence.

Unified vs separate: Both the EU 2023 and the US 2025 guidelines now unify STEMI and NSTEMI into a single ACS document — convergence in approach (the US previously had separate 2013 STEMI and 2014 NSTEMI guidelines).

Invasive timing for NSTE-ACS: EU gives early invasive (within 24h) a Class IIa for high-risk NSTE-ACS (downgraded from previous Class I). The US 2025 guideline's approach to invasive timing should be compared once reviewed.

DAPT de-escalation: EU provides more granular Class IIa/IIb options for stepping down DAPT after 3–6 months. The US guideline's de-escalation framework will need direct comparison.

Pending: Full US vs EU comparison to be completed after US 2025 ACC/AHA ACS guideline is reviewed in detail.

Correction notice: A correction was published Apr 1, 2024 (doi: 10.1093/eurheartj/ehad870).

Full guideline replacement: Supersedes both the 2017 ESC STEMI guideline and the 2020 ESC NSTE-ACS guideline entirely.

Total recommendations: 193 recommendations (106 Class I, 70 Class II, 17 Class III). 56 with Level of Evidence A, 64 Level B, 73 Level C.

Link to other ESC guidelines: Lipid-lowering and secondary prevention recommendations in this ACS guideline are complemented by the 2025 ESC/EAS dyslipidemia focused update (which specifically addresses early intensive LDL-C lowering during index ACS hospitalization) and the 2024 ESC chronic coronary syndromes guideline for long-term management post-ACS.

New diagnostic model — Risk Factor-weighted Clinical Likelihood (RF-CL): Replaces the 2019 basic pre-test probability model. Incorporates age, sex, symptoms, and CV risk factors to better estimate likelihood of obstructive CAD. Patients with very low (≤5%) RF-CL can defer further testing (Class IIa). For low likelihood (5–15%), coronary artery calcium scoring (CACS) recommended to reclassify (Class IIa).

CCTA as first-line non-invasive test (Class I, Level A): For patients with low-to-moderate (>5–50%) pre-test likelihood. Stress imaging (echo, SPECT/PET, CMR) recommended for moderate-to-high (>15–85%) likelihood (Class I). Contrast-enhanced stress echo with microbubbles now Class I for improving diagnostic accuracy.

ANOCA/INOCA framework expanded: Angina with No Obstructive Coronary Arteries / Ischemia with No Obstructive Coronary Arteries now has its own dedicated diagnostic and treatment pathway. Coronary functional testing (acetylcholine, adenosine) recommended to identify vasospasm/microvascular dysfunction. Medical therapy guided by functional test results (Class IIa). ACE-I for endothelial dysfunction (Class IIa).

Antithrombotic therapy: Clopidogrel 75 mg now recommended as a safe and effective alternative to aspirin monotherapy after MI or PCI (Class I, Level A) — a notable shift. Aspirin remains Class I after CABG. For patients without prior MI/revascularization but with significant obstructive CAD, aspirin 75–100 mg recommended lifelong (Class I).

Lipid-lowering: LDL-C goal <1.4 mmol/L (55 mg/dL) for CCS patients (Class I). Ezetimibe + bempedoic acid combination now Class I when statins insufficient.

SGLT2 inhibitors & GLP-1 receptor agonists (Class I, Level A): In CCS patients with T2DM for CV risk reduction, independent of HbA1c. Semaglutide also considered (Class IIa) for CCS patients without diabetes but with overweight/obesity (BMI ≥27) to reduce CV mortality, MI, or stroke — a major new recommendation reflecting SELECT trial data.

Low-dose colchicine (Class IIa): 0.5 mg daily in CCS patients with atherosclerotic CAD to reduce MI, stroke, and need for revascularization — based on LoDoCo2 and COLCOT trials.

Revascularization: Heart Team discussion recommended for complex cases (Class I). CABG and PCI indications refined with individual patient-level data analyses. Emphasis on shared decision-making.

Diagnostic approach: EU 2024 introduces the RF-CL model as the primary tool; US 2023 AHA/ACC CCD guideline uses a different pre-test probability estimation. EU gives stronger emphasis to CCTA as first-line for low-to-moderate risk; US also endorses CCTA but with more flexibility across testing modalities.

Clopidogrel as aspirin alternative: EU now gives clopidogrel monotherapy a Class I recommendation as an alternative to aspirin post-MI/PCI — the US guideline has not made this same upgrade, still generally favouring aspirin as default monotherapy.

Colchicine: EU gives Class IIa; US 2023 CCD guideline gives a weaker endorsement. Both acknowledge LoDoCo2/COLCOT data but differ on confidence level.

SGLT2i/GLP-1 RA for non-diabetic patients: EU's Class IIa for semaglutide in overweight/obese CCS patients without diabetes (based on SELECT trial) is a novel recommendation not yet mirrored in the US CCD guideline, which predates SELECT's full publication.

ANOCA/INOCA: EU 2024 provides a much more comprehensive framework for diagnosing and treating non-obstructive coronary disease than the US guideline, which addresses it more briefly.

Correction notice: A correction was published Apr 22, 2025 (doi: 10.1093/eurheartj/ehaf079).

Full guideline replacement: This replaces the 2019 ESC CCS guideline entirely. The change in terminology from "stable ischemic heart disease" to "chronic coronary syndromes" (started in 2019) is continued, reflecting the dynamic nature of the condition.

Professor Collet memorial: Prof. Jean-Philippe Collet passed away during development of this guideline; his contribution is acknowledged by the Task Force.

Key trials informing update: REVIVED-BCIS2 (PCI vs OMT in ischemic LV dysfunction — neutral), ORBITA-2 (PCI vs placebo for angina relief — positive), SELECT (semaglutide for CV events in obesity — positive), LoDoCo2 and COLCOT (colchicine — positive).

Annual "living" guideline: Updated every January by the ADA Professional Practice Committee (PPC). Unlike ESC/ACC guidelines that follow irregular multi-year cycles, the ADA Standards of Care is revised annually with systematic literature review (PubMed/Medline/EMBASE, Jun 2024 – Jul 2025 for the 2026 edition). Most recent full review and revision completed December 2025. Interim "living standards" updates are published online when urgent new evidence or regulatory changes warrant immediate inclusion.

Comprehensive scope: Covers T1DM, T2DM, gestational diabetes, and other hyperglycemic conditions across the entire lifespan (children, adolescents, adults, older adults). Sections span from prevention and screening through glycemic management, CV risk management, CKD, obesity/weight management, technology, pregnancy, and complications.

Multi-society endorsements (2026): ACC endorses section 10 (Cardiovascular Disease and Risk Management). NKF endorses section 11 (CKD — new for 2026). ISPAD endorses section 14 (Children and Adolescents — new for 2026). Also endorsed: AGS (Older Adults), TOS (Obesity), ASBMR (Bone Health).

Key pharmacotherapy pillars for T2DM with CV/renal risk: GLP-1 receptor agonists with proven CV benefit (e.g., semaglutide, liraglutide, dulaglutide) and SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) are recommended independent of HbA1c for patients with established ASCVD, HF, or CKD. This aligns with ESC guidance but the ADA provides more granular drug-selection algorithms specific to diabetes phenotypes.

Glycemic targets: HbA1c <7% (53 mmol/mol) for most non-pregnant adults. More stringent (<6.5%) may be appropriate if achievable without significant hypoglycemia. Less stringent (<8%) for those with limited life expectancy, advanced complications, extensive comorbidity, or long-standing diabetes where the target is hard to achieve.

Obesity/weight management (Section 8): Increasingly prominent section reflecting the growing role of GLP-1 RA and dual GIP/GLP-1 RA (tirzepatide) for weight management in people with T2DM. The 2026 edition likely reflects expanded indications and data from SURMOUNT and SURPASS trial programs.

EU counterpart — ESC 2023 CVD in Diabetes: The 2023 ESC Guidelines for CVD in Diabetes is the European gold standard for managing cardiometabolic patients. While it does not match the ADA's comprehensive scope (it focuses specifically on CV risk and CVD manifestations in diabetes, not glycemic management, technology, or diabetes subtypes beyond T2DM), it is the primary reference for European cardiologists and internists. The EASD collaborates with ADA on consensus reports but does not publish its own annual Standards of Care.

CV risk stratification — SCORE2-Diabetes: New 10-year CVD risk prediction model for T2DM patients aged ≥40 without established CVD or severe target organ damage. Classifies into moderate, high, and very high risk categories. Patients with established ASCVD, HF, AF, or severe CKD are automatically very high risk without needing SCORE2-Diabetes.

Screening — "treat CV risk, not just glucose": Screen all CVD patients for diabetes (fasting glucose + HbA1c). Screen all diabetes patients for CVD symptoms, HF signs, and CKD. Systematic HF screening at every clinical encounter (Class I).

Glucose-lowering agents with proven CV benefit (Class I): GLP-1 RA (liraglutide, semaglutide SC, dulaglutide, efpeglenatide) and SGLT2i (empagliflozin, canagliflozin, dapagliflozin, sotagliflozin) recommended for T2DM patients with ASCVD to reduce CV events — independent of HbA1c or baseline glucose control. SGLT2i recommended in T2DM with HF (any EF) and in T2DM with CKD (eGFR ≥20). Finerenone recommended for T2DM with CKD and albuminuria despite maximised RASi.

Multifactorial risk management: Intensive lipid-lowering (LDL-C targets per ESC dyslipidaemia guidelines). BP control. Antiplatelet therapy per clinical context. Emphasis on personalised, interdisciplinary approach across cardiology, endocrinology, nephrology, and primary care.

Scope narrowing vs 2019: Deliberately drops pre-diabetes (insufficient treatment evidence). Focuses exclusively on CVD and diabetes — refers to EASD/ADA for glycemic management, lifestyle, and diabetes subtypes.

Scope — the fundamental divergence: The ADA Standards of Care is a comprehensive, annually updated, all-of-diabetes document (T1DM, T2DM, gestational, glycemic targets, technology, prevention, screening, complications). The ESC 2023 guideline is a CV-specialist document focused specifically on preventing and managing CVD manifestations in patients who happen to have diabetes. They are complementary rather than competing — but clinicians reading only one will have significant blind spots.

Risk stratification: ADA uses the PREVENT calculator (2023 AHA, incorporates CKM factors) for ASCVD + HF risk. ESC uses SCORE2-Diabetes for 10-year CVD risk in T2DM patients without established CVD. Both identify the same high-risk patients but via different scoring systems.

Pharmacotherapy convergence: Both recommend GLP-1 RA and SGLT2i for T2DM patients with established CVD, HF, or CKD — independent of glycemic control. This is the area of strongest agreement. The ESC guideline names specific agents with proven CV benefit; the ADA provides more granular drug-selection algorithms by diabetes phenotype and comorbidity profile.

Glycemic targets: ADA provides detailed HbA1c target recommendations (<7% general, with individualised ranges). The ESC guideline deliberately defers to EASD/ADA for glycemic management, offering only broad principles (individualised targets, avoid hypoglycemia).

Update cycle: ADA is updated annually (January). ESC follows an irregular multi-year cycle (2019 → 2023, next update TBD). This means the ADA incorporates newer trial data more quickly, while the ESC guideline provides a more stable, longer-lived reference for European practice.

Supersedes all prior ADA documents: The Standards of Care explicitly supersedes all previously published ADA scientific documents on clinical topics within its scope.

Evidence grading: Uses A/B/C/E system (A = well-conducted RCTs/meta-analyses; B = RCTs with limitations or good cohort studies; C = poorly controlled studies; E = expert consensus). This differs from the ESC Class I–III / Level A–C system, making direct recommendation-strength comparisons non-trivial.

Cross-references: The ADA CV section (10) and the ESC 2023 CVD in Diabetes guideline overlap substantially with ESC guidelines on heart failure, dyslipidemia, hypertension, and CKD listed on this page. The SCORE2-Diabetes algorithm is the ESC's primary CV risk tool for T2DM patients; the AHA's PREVENT calculator (adopted in the 2026 Dyslipidemia Guideline and CKM advisory) is the US counterpart.

Technology section: Uniquely comprehensive coverage of continuous glucose monitoring (CGM), insulin pump therapy, automated insulin delivery (AID) systems, and digital health tools — areas not addressed in ESC guidelines.

ACC Concise Clinical Guidance (CCG) — pharmacotherapy-first approach: Recommends considering anti-obesity medications as a first-line treatment option for eligible patients alongside lifestyle interventions. Patients should not be required to "try and fail" lifestyle changes before initiating pharmacotherapy. GLP-1 receptor agonist semaglutide and dual GIP/GLP-1 receptor agonist tirzepatide identified as the most effective agents.

Eligibility: Pharmacotherapy appropriate for BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one obesity-related comorbidity. Weight loss thresholds associated with specific comorbidity improvements are provided.

CV risk reduction: Clinical evidence supports GLP-1 RA and GIP/GLP-1 RA medications leading to reduction in major adverse cardiovascular events (MACE), particularly in individuals with T2DM and elevated CV risk (SELECT trial data).

ACC Scientific Statement on Obesity in HF: Companion document focused on HFpEF. Semaglutide (STEP-HFpEF) and tirzepatide (SUMMIT) associated with reduction in HF symptoms. Benefit currently established for HFpEF only; safety and efficacy in HFrEF not yet established.

EASO 2024 Diagnostic Framework: Redefines obesity as an adiposity-based chronic disease. Diagnosis should be based on both anthropometric (BMI + waist-to-height ratio >0.5) and clinical components (medical, functional, psychological complications). Moves beyond BMI-only thresholds. Introduces staging by complication severity.

EASO 2025 Pharmacological Framework: First GRADE-based treatment algorithm for obesity pharmacotherapy in Europe. Treatment selection guided by presence or absence of specific obesity-related complications. Tirzepatide and semaglutide recommended as first-line agents across most indications. Tirzepatide preferred for OSA and MASH; semaglutide preferred for established CVD (MACE reduction) and knee osteoarthritis. Liraglutide and naltrexone–bupropion positioned as second-line options.

Annual updates planned: EASO intends to update the pharmacological framework annually as new evidence becomes available (2026 edition already in preparation with extended data cutoff).

Document type divergence: The US documents are an ACC expert consensus statement (CCG) and a scientific statement — not formal AHA/ACC clinical practice guidelines with Class/Level recommendations. The EU documents are EASO frameworks — also not ESC guidelines. Neither side has published a formal Class I/Level A clinical practice guideline specifically for obesity management as a primary CV prevention strategy. The closest formal guideline touching obesity is the US 2013 AHA/ACC/TOS Obesity Guideline, which is substantially outdated.

Convergence on pharmacotherapy-first: Both US and EU now recommend that pharmacotherapy should be considered early, without requiring failure of lifestyle interventions first. Both identify semaglutide and tirzepatide as the leading agents.

Complication-based selection (EU): The EASO 2025 framework provides a more granular, complication-specific treatment algorithm than the ACC CCG, mapping individual medications to specific conditions (T2DM, CVD, HF, MASH, OSA, OA). The ACC CCG is broader in scope but less prescriptive on drug selection per complication.

Diagnostic criteria: EASO's 2024 framework explicitly moves beyond BMI with waist-to-height ratio and clinical staging. The ACC CCG acknowledges BMI limitations but does not formally propose an alternative diagnostic framework.

No formal AHA/ACC or ESC clinical practice guideline: It is notable that neither the AHA/ACC nor the ESC has yet published a dedicated, full clinical practice guideline for obesity as a primary CV risk driver. The US 2013 AHA/ACC/TOS Obesity Guideline is over a decade old and predates all GLP-1 RA/GIP evidence. A formal guideline update is anticipated but not yet announced.

Key trials: SELECT (semaglutide 2.4 mg — 20% MACE reduction in overweight/obese adults with CVD but without diabetes), STEP-HFpEF (semaglutide — symptom benefit in HFpEF), SUMMIT (tirzepatide — HF events reduction in HFpEF), SURMOUNT (tirzepatide — weight loss in obesity ± T2DM), ESSENCE (semaglutide — MASH improvement).

Cross-references: Obesity management recommendations are also embedded in: ADA Standards of Care 2026 (Section 8), ESC 2024 CCS guideline (semaglutide for overweight CCS patients — Class IIa), KDIGO 2024 CKD guideline, and the AHA 2023 CKM Syndrome advisory. This card focuses on obesity-specific guidance documents; the cross-cutting clinical recommendations are noted in those respective condition cards.

First formal definition of CKM syndrome: A systemic disorder characterized by the pathophysiological interactions among metabolic risk factors (obesity, T2DM, metabolic syndrome), chronic kidney disease, and cardiovascular disease. The primary driver is excess or dysfunctional adiposity, which triggers a cascade of insulin resistance, inflammation, and organ damage across cardiac, renal, and metabolic systems.

Four-stage classification: Stage 0 — no CKM risk factors. Stage 1 — excess adiposity (overweight/obesity). Stage 2 — metabolic risk factors (T2DM, hypertension, dyslipidemia, metabolic syndrome) and/or moderate-to-high-risk CKD. Stage 3 — subclinical CVD in the setting of CKM risk factors or high predicted CVD risk (using PREVENT equations). Stage 4 — clinical CVD (subdivided into 4a: CVD without kidney failure and 4b: CVD with kidney failure).

PREVENT risk calculator: Replaced the older pooled cohort equations (PCE). Starts at age 30 (PCE started at 40). Incorporates eGFR, urine albumin-to-creatinine ratio, HbA1c, and social deprivation index alongside traditional risk factors. Predicts 10-year and 30-year risk of total CVD including heart failure (not just ASCVD). Now adopted in the 2026 ACC/AHA Dyslipidemia Guideline.

Stage-based screening and management: Age-based screening from childhood onward. SGLT2 inhibitors and GLP-1 receptor agonists positioned as key cross-cutting therapies for Stages 2–4, with finerenone for diabetic kidney disease. Multidisciplinary care teams (cardiology, nephrology, endocrinology, primary care) recommended for patients with ≥2 CKM criteria.

Social determinants of health: Prominent integration of SDOH into both risk assessment and management — a distinguishing feature of this advisory. Disproportionate burden among racial/ethnic minorities and socioeconomically disadvantaged populations.

Advisory, not a guideline: This is an AHA Presidential Advisory accompanied by a Scientific Statement — not a formal AHA/ACC Joint Clinical Practice Guideline with Class/Level of Evidence recommendations. However, it is being widely adopted as a clinical framework for integrating SGLT2i and GLP-1 RA across renal and cardiac specialties, and the PREVENT calculator has been incorporated into formal guidelines (2026 Dyslipidemia Guideline).

No EU equivalent: There is no ESC or EASO counterpart document that defines CKM syndrome as a unified construct. However, the concept is implicitly reflected across multiple ESC guidelines: the 2024 ESC Hypertension Guideline, 2024 ESC CCS Guideline (SGLT2i/GLP-1 RA in CCS with T2DM), 2023 ESC HF Focused Update (SGLT2i + finerenone for T2DM + CKD), and KDIGO 2024 CKD Guideline. The EU approach remains disease-specific rather than syndrome-level.

CKM Health Initiative (2024–2028): The AHA launched a four-year CKMH Initiative in 2024 to implement the advisory's framework, including care coordinator certification, clinical site guidance, and community-based organization partnerships. ~89 million US adults estimated to have ≥3 CKM risk factors.

Cross-references on this page: CKM syndrome bridges the Diabetes, CKD, Obesity, Heart Failure, and Dyslipidemia cards on this page. The PREVENT calculator is referenced in the 2026 Dyslipidemia Guideline. SGLT2i and GLP-1 RA recommendations appear in CKD (KDIGO 2024), HF (ESC 2023 update), CCS (ESC 2024), and ADA Standards of Care 2026.

SGLT2 inhibitors — expanded to non-diabetic CKD (1A): Recommended for T2D + CKD + eGFR ≥20 (1A). Also now recommended for adults with CKD without diabetes if eGFR ≥20 with ACR ≥200 mg/g, or with heart failure irrespective of albuminuria (1A). Suggested (2B) for eGFR 20–45 even without significant albuminuria. Once initiated, reasonable to continue even if eGFR drops below 20.

Nonsteroidal MRA — finerenone (2A): Suggested for adults with T2D, eGFR >25, normal serum K+, and albuminuria (>30 mg/g) despite maximally tolerated RASi. Most appropriate for those at high risk of CKD progression and CV events. Requires potassium monitoring (at 1 month, then every 4 months). Specific dosing guidance: 10 mg if eGFR 25–59, 20 mg if eGFR ≥60.

RAS inhibitors: Recommended for CKD with severely increased albuminuria (A3) without diabetes (1B) and with diabetes (1B). Suggested for moderately increased albuminuria (A2) without diabetes (2C). Combination of ACEi + ARB + DRI is not recommended (Class III).

Blood pressure target: SBP <120 mmHg suggested when tolerated using standardized office measurement (2B). Aligns with ESC 2024 hypertension guideline's intensive target direction.

GLP-1 receptor agonists: Recommended for adults with T2D and CKD not at individualized glycemic targets despite metformin + SGLT2i (or unable to use them) — to reduce CKD progression and CV events.

GFR estimation: Creatinine-based eGFR (eGFRcr) recommended as initial approach (1A). If cystatin C available, combination (eGFRcr-cys) recommended for more accurate categorization (1B).

Protein intake: 0.8 g/kg/day suggested for CKD G3–G5 (2C). High protein intake (>1.3 g/kg/day) should be avoided in adults at risk of progression.

CV risk management: Lipid-modifying therapy recommended to reduce CV risk. Low-dose aspirin for secondary prevention (1C). Antiplatelet alternatives (P2Y12) when aspirin-intolerant.

Models of care: Comprehensive chapter on multidisciplinary teams, self-management, telehealth, and care coordination — reflecting KDIGO's emphasis on implementation.

Global standard — no separate US/EU versions: KDIGO guidelines are used worldwide and explicitly referenced by both ESC and ADA guidelines. The 2024 CKD guideline is the primary global reference, replacing the 2012 KDIGO CKD guideline after a 12-year gap.

Cross-references to other KDIGO guidelines: This CKD guideline references and builds on KDIGO 2021 BP in CKD, KDIGO 2022 Diabetes in CKD, KDIGO 2024 CKD-MBD update, and KDIGO 2012 Anemia in CKD. The SGLT2i and finerenone recommendations are harmonized with the 2022 diabetes-CKD guideline but extended here to non-diabetic CKD.

Key trials informing this update: DAPA-CKD (dapagliflozin in CKD ± diabetes), EMPA-KIDNEY (empagliflozin in CKD), FIDELIO-DKD and FIGARO-DKD (finerenone in diabetic kidney disease), CREDENCE (canagliflozin in diabetic nephropathy).

Alignment with ESC/ADA: SGLT2i and finerenone recommendations are broadly consistent with the 2023 ESC HF focused update (which recommends SGLT2i + finerenone for T2D + CKD for HF prevention) and the ADA 2026 Standards of Care (NKF now endorses ADA's CKD section). The BP target of <120 mmHg SBP aligns with the ESC 2024 hypertension guideline's intensive direction.

Open access: Published under CC BY-NC-ND license — free to access, which is unusual for major guidelines and important for global implementation.

Aortic stenosis — TAVI as primary treatment for ≥70 (Class I, Level B): TAVI recommended as the primary treatment modality in elderly patients ≥70 years with a tricuspid aortic valve, if anatomy is suitable and transfemoral access is feasible. SAVR preferred for patients <70 years at low surgical risk. For all other bioprosthesis candidates, the Heart Team selects the optimal approach considering procedural risk, anatomy, comorbidities, expected outcomes, durability, and patient preference.

Asymptomatic severe AS — intervention considered (Class IIa, Level A): In asymptomatic patients with severe high-gradient AS and LVEF ≥50%, intervention should be considered as an alternative to close surveillance if procedural risk is low — a notable upgrade reflecting EARLY TAVR and EVoLVeD trial data.

Non-transfemoral TAVI (Class IIa): Should be considered for patients unsuitable for surgery and transfemoral access. TAVI for bicuspid AS may be considered (Class IIb) at increased surgical risk if anatomy suitable.

Primary mitral regurgitation: MV repair remains preferred over replacement when durable results expected. Transcatheter edge-to-edge repair (M-TEER) options expanded for selected patients at high surgical risk.

Secondary mitral regurgitation: GDMT optimization (including CRT if indicated) remains first-line. M-TEER recommended based on COAPT criteria (reduced HF hospitalization and mortality at 2 and 5 years). MITRA-FR showed no benefit — differences likely due to patient selection.

Tricuspid regurgitation: Dedicated expanded section with stepwise evaluation and management pathway. Transcatheter tricuspid interventions increasingly recognized for selected patients with severe TR.

Heart Valve Centres: Strong emphasis on referral to high-volume, multidisciplinary centres for complex procedures. Specific requirements defined (Table 5). Heart Team decision-making for all complex cases (Class I).

Antithrombotic therapy: Mechanical valves require lifelong VKA (DOACs contraindicated). For bioprosthetic valves and AF, DOACs should be avoided in patients with MVA ≤2.0 cm². Surgical LAA closure recommended as adjunct to OAC during valve surgery in patients with AF (Class I).

Diagnostic imaging: CCTA recommended before valve intervention for patients with moderate/reduced pretest likelihood of obstructive CAD. Invasive coronary angiography for high/very high pretest likelihood. CT calcium scoring for aortic stenosis severity assessment in discordant low-gradient cases.

Critical timing gap: The US guideline is from 2020; the EU guideline is 2025 — a 5-year gap during which major TAVI trials (DEDICATE, EARLY TAVR, EVoLVeD, UK TAVI) and transcatheter mitral/tricuspid intervention data have been published. The EU 2025 guideline reflects substantially more current evidence.

TAVI age thresholds: The US 2020 guideline gives TAVI a Class 1 indication for patients at high/prohibitive surgical risk and Class 2a for intermediate risk, without a specific age-based primary recommendation. The EU 2025 guideline explicitly recommends TAVI as primary treatment for ≥70 years (tricuspid AV, suitable anatomy, transfemoral access) — a much more prescriptive age-based approach.

Asymptomatic severe AS: EU 2025 upgrades intervention for asymptomatic severe AS to Class IIa based on EARLY TAVR/EVoLVeD. The US 2020 guideline is more conservative (Class IIa only with very specific criteria like exercise test abnormality or very severe stenosis).

Tricuspid interventions: EU 2025 provides a comprehensive transcatheter tricuspid intervention framework that did not exist in the US 2020 guideline (TRILUMINATE Pivotal and other data were not yet available).

A US update is overdue: Given the 5-year evidence gap, the US 2020 VHD guideline is the most outdated guideline on this page relative to its EU counterpart. An ACC/AHA update is anticipated but not yet published.

Full guideline replacement: Replaces the 2021 ESC/EACTS VHD guideline entirely (which itself replaced the 2017 version).

Key trials informing update: DEDICATE (TAVI vs SAVR in intermediate-risk), EARLY TAVR (intervention vs surveillance in asymptomatic severe AS), EVoLVeD (LGE-guided intervention in asymptomatic AS), UK TAVI (TAVI vs SAVR in over-65s), COAPT (M-TEER for secondary MR — 5-year data), TRILUMINATE Pivotal (transcatheter tricuspid repair).

Durability concerns acknowledged: Long-term durability of transcatheter valves remains a key consideration, particularly for younger patients where anticipated life expectancy may exceed valve durability. SAVR with mechanical valves remains the standard for younger patients who accept lifelong anticoagulation.

Undertreatment as a major theme: The guideline explicitly aims to reduce underdiagnosis and undertreatment of VHD, particularly in the elderly — noting that this contributes to unnecessary healthcare resource use and shortened lifespan.

Four clinical subsets: The guideline defines a new clinical framework with four PAD presentation subsets: asymptomatic PAD (may have functional impairment), chronic symptomatic PAD (including claudication), chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI). Management pathways are defined for each subset.

Screening: Ankle-brachial index (ABI) recommended as the first-line screening tool. ABI ≤0.90 diagnostic for PAD. Toe-brachial index, segmental pressures, and exercise ABI for inconclusive resting ABI.

Medical therapy — expanded: High-intensity statin to lower LDL-C by ≥50% (Class I). Antiplatelet therapy: single antiplatelet (aspirin or clopidogrel) for all symptomatic PAD. Low-dose rivaroxaban (2.5 mg BID) + aspirin recommended for patients at high ischaemic risk and low bleeding risk — based on COMPASS trial data. GLP-1 RA and SGLT2i recommended for PAD patients with T2DM to reduce MACE.

Structured exercise therapy: Supervised exercise therapy (SET) recommended as first-line for claudication (Class I). Home-based exercise programs as alternative when SET is unavailable.

CLTI management: WIfI classification (Wound, Ischemia, foot Infection) recommended for risk stratification. Multidisciplinary limb preservation teams recommended. Revascularization decisions guided by anatomic, clinical, and patient factors.

Health disparities: Strong emphasis on addressing racial, ethnic, and socioeconomic disparities in PAD diagnosis, treatment, and amputation rates — a new focus compared to 2016.

Merged guideline: First ESC guideline to combine peripheral arterial diseases and aortic diseases into a single document, replacing both the 2017 ESC PAD guideline and the 2014 ESC aortic diseases guideline. Emphasises comprehensive evaluation of the entire arterial circulation in all PAAD patients (Class I, Level B).

Lower extremity PAD — pharmacotherapy: Single antiplatelet therapy (aspirin or clopidogrel) recommended for symptomatic PAD (Class I, Level A). Dual antithrombotic therapy with low-dose rivaroxaban + aspirin should be considered in patients at high ischaemic risk and low bleeding risk (Class IIa, Level A) — aligning with the US recommendation on COMPASS-based data.

Aortic diseases: Surgery for ascending aortic aneurysm recommended at ≥55 mm (Class I, Level B — now incorporating parameters beyond diameter alone). New TEM classification for acute aortic syndromes (Type, Entry tear location, Malperfusion). Expanded endovascular treatment recommendations.

Multidisciplinary approach: Complex cases should be managed at specialised, high-volume PAAD centres. Shared decision-making between patients and physicians emphasised throughout.

Scope: The US 2024 guideline covers lower extremity PAD only. The EU 2024 guideline covers both peripheral arterial diseases (including lower extremity, carotid, renal, mesenteric) and aortic diseases in a single document — substantially broader scope.

Publication timing: Both published in 2024 (US May, EU August) and reflect similar evidence bases — an unusually well-matched guideline cycle.

Antithrombotic therapy convergence: Both recommend single antiplatelet therapy for symptomatic PAD (Class I) and low-dose rivaroxaban + aspirin for high ischaemic/low bleeding risk (US Class I, EU Class IIa — modest difference in recommendation strength).

Health disparities emphasis: The US guideline places significantly more emphasis on racial, ethnic, and socioeconomic disparities in PAD care and amputation rates. The EU guideline focuses more on access to high-volume specialist centres.

Correction notices: US guideline corrected Apr 7, 2025 (doi: 10.1161/CIR.0000000000001329).

PAD as a CV risk equivalent: Both guidelines reinforce that PAD signals high systemic atherosclerotic burden. Patients with PAD have substantially elevated risk of MI, stroke, and CV death — often higher than isolated coronary disease.

Key trials informing updates: COMPASS (rivaroxaban + aspirin in PAD), VOYAGER PAD (rivaroxaban post-revascularisation), BEST-CLI (bypass vs endovascular for CLTI), BASIL-2 (vein-first strategy for CLTI), SELECT (semaglutide in overweight/obesity with CVD).

Cross-references on this page: PAD medical therapy aligns with the Dyslipidemia (high-intensity statin), Hypertension, Diabetes (SGLT2i/GLP-1 RA), and CKD cards. The CKM Syndrome advisory includes PAD as part of Stage 4 clinical CVD.