Cardio · ischaemic-heart-disease
DAPT complications: bleeding, switching and surgery
Fellowship-level guide to the hard decisions in dual antiplatelet therapy after acute and chronic coronary syndromes, built from the 2023 ESC and 2025 ACC/AHA acute coronary syndrome guidelines, the 2024 ESC and 2023 AHA/ACC chronic coronary guidelines, the 2024 ESC and 2023 ACC/AHA atrial fibrillation guidelines, the 2022 ESC non-cardiac surgery guideline and the 2025 NHFA/CSANZ ACS guideline: default duration, abbreviation and de-escalation, switching between P2Y12 inhibitors, the ARC high bleeding risk criteria as printed, gastric protection, triple therapy with an oral anticoagulant, transfusion and bleeding, and interruption of antiplatelet therapy for cardiac and non-cardiac surgery.
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Red flags
- ESC 2022: premature interruption of DAPT in patients with recent coronary stent implantation is the strongest predictor of stent thrombosis
- ESC 2023: de-escalation of antiplatelet therapy in the first 30 days after an ACS event is not recommended (Class III, Level B)
- ESC 2023: the use of ticagrelor or prasugrel as part of triple antithrombotic therapy is not recommended (Class III, Level C)
- ACC/AHA 2025: in patients with a history of stroke or transient ischaemic attack, prasugrel should not be administered because of worse net clinical outcomes (COR 3: Harm, LOE B-R)
This page is about the hard part of antiplatelet therapy: the patient who bleeds, the patient who needs a different drug, and the patient who needs an operation. Each decision trades stent thrombosis and recurrent ischaemia against bleeding, and each guideline frames that trade a little differently.[1][2]
- Related topic: STEMI: reperfusion.
- Related topic: NSTE-ACS management.
- Related topic: Secondary prevention after ACS.
- Related topic: Atrial fibrillation.
Why bleeding on DAPT matters
Start with the patient three weeks after a stent who arrives with melaena.[1] ESC 2023 says bleeding is associated with a poor prognosis in ACS patients, and that major bleeding affects prognosis in a similar way to spontaneous ischaemic complications.[1]
- Mechanisms (ESC 2023): the mechanisms by which bleeding increases the risk of death are complex and multifactorial; intracranial or massive haemorrhage threatens life directly, while less severe bleeding may increase the risk of death through indirect mechanisms.[1]
- Transfusion (ESC 2023): blood transfusion may increase systemic inflammation and is one of the possible links between bleeding and subsequent mortality.[1]
- Interruption (ESC 2023): bleeding is a major driver of unplanned DAPT discontinuation and of interruption of other medication, such as statins and beta-blockers.[1]
- The loop (ACC/AHA 2025): prolonged exposure to DAPT results in excess bleeding that may lead to DAPT interruption, which in turn may increase the risk of recurrent ischaemic events.[2]
Time is on your side.[1] ESC 2023 notes that after PCI for ACS, ischaemic and bleeding events both markedly decrease over time.[1] It adds that risk scores may be useful to tailor antithrombotic duration and intensity, to maximise ischaemic protection and minimise bleeding risk in the individual patient.[1]
Terms and definitions
Learn the vocabulary first, because every recommendation is written in it. ESC 2023 describes the default after PCI as DAPT with a potent P2Y12 receptor inhibitor (prasugrel or ticagrelor) and aspirin, generally recommended for 12 months irrespective of stent type unless there are contraindications.[1] In specific clinical scenarios, that default can be shortened (under 12 months), extended (over 12 months) or modified by switching or de-escalation.[1]
The words the guidelines use
| Term | As the source states it |
|---|---|
| De-escalation (ESC 2023) | Switching from prasugrel or ticagrelor to clopidogrel |
| De-escalation (ACC/AHA 2025) | Modulating DAPT intensity by switching from ticagrelor or prasugrel to clopidogrel |
| Guided de-escalation (ACC/AHA 2025) | Guided by platelet function assays: patients with adequate response may continue clopidogrel, whereas non-responders are switched to a more potent P2Y12 inhibitor; responsiveness may also be inferred with genotyping assays |
| Unguided de-escalation (ACC/AHA 2025) | Performed without antecedent knowledge of platelet responsiveness |
| Abbreviated DAPT (ESC 2023) | One of the two groups of antiplatelet strategies to reduce bleeding risk in the first 12 months after an ACS (the other is DAPT de-escalation); the alternatives include shortening the DAPT duration to 1 or 3–6 months, depending on the balance of bleeding and ischaemic risks |
| Triple antithrombotic therapy, TAT (ESC 2023) | (N)OAC + DAPT (Figure 12); in the default regimen, a NOAC with aspirin and clopidogrel |
| Dual antithrombotic therapy, DAT (ESC 2023) | (N)OAC + single antiplatelet therapy, SAPT (Figure 12); in the default regimen, a NOAC at the recommended dose for stroke prevention with SAPT, preferably clopidogrel |
Pharmacology that drives the decisions
Two properties matter at the bedside: how the drug blocks the platelet, and how long the effect lasts after the last dose.[7] ESC 2022 tabulates both in its Table 7.[7]
Antiplatelet pharmacology (ESC 2022 NCS, Table 7; selected columns)
| Drug | Application | Target (type of blockade) | Prodrug | Plasma half-life | Duration of action after last dose |
|---|---|---|---|---|---|
| Aspirin | Oral | COX-1 (irreversible) | No | 20 min | 7–10 days |
| Clopidogrel | Oral | P2Y12 (irreversible) | Yes | 0.5–1 h (active metabolite) | 3–10 days, depending on response status |
| Prasugrel | Oral | P2Y12 (irreversible) | Yes | 0.5–1 h (active metabolite) | 7–10 days, depending on response status |
| Ticagrelor | Oral | P2Y12 (reversible) | No | 6–12 h | 3–5 days |
| Cangrelor | i.v. | P2Y12 (reversible) | No | 3–6 min | 1–2 h |
- Clopidogrel (ACC/AHA 2025): the least potent oral P2Y12 inhibitor; it requires biotransformation in the liver to its active metabolite, so it takes more time to reach maximal platelet inhibition after a loading dose.[2]
- Variable response (ACC/AHA 2025): pharmacodynamic variability in response to clopidogrel has been well described, and hyporesponders may be at increased risk of MACE and stent thrombosis when treated with clopidogrel after PCI.[2]
- Ticagrelor and prasugrel (ACC/AHA 2025): more potent than clopidogrel, with more rapid onset of inhibition of platelet activation, but with increased risk of bleeding compared with clopidogrel.[2]
- Dyspnoea (ACC/AHA 2025): ticagrelor may cause subjective transient dyspnoea in approximately 10% to 15% of patients after ACS.[2]
- Aspirin dose with ticagrelor (ACC/AHA 2025): aspirin doses of 100 mg daily or less should always be used in patients treated with ticagrelor.[2]
Oral antiplatelet doses in ACS, by guideline
| Drug | ESC 2023 (Recommendation Table 5) | ACC/AHA 2025 (Table 7) |
|---|---|---|
| Aspirin | Initial oral loading dose 150–300 mg (or 75–250 mg i.v.), maintenance 75–100 mg once daily for long-term treatment, recommended for all patients without contraindications (Class I, Level A) | For NSTE-ACS or STEMI: loading 162–325 mg orally, chewed when possible (non-enteric coated); loading dose given even to patients already on aspirin; maintenance 75–100 mg daily (non-enteric coated) |
| Prasugrel | 60 mg loading, 10 mg once daily; 5 mg once daily for patients aged 75 years or more or weighing under 60 kg; recommended in P2Y12 inhibitor-naïve patients proceeding to PCI (Class I, Level B) | For NSTE-ACS or STEMI without fibrinolytic, and undergoing PCI: loading 60 mg; maintenance 10 mg daily if body weight 60 kg or more and age under 75 years, or 5 mg daily if body weight under 60 kg or age 75 years or more (use caution) |
| Ticagrelor | 180 mg loading, 90 mg twice daily; recommended irrespective of the treatment strategy, invasive or conservative (Class I, Level B) | For NSTE-ACS or STEMI without fibrinolytic: loading 180 mg; maintenance 90 mg twice daily |
| Clopidogrel | 300–600 mg loading, 75 mg once daily; recommended when prasugrel or ticagrelor are not available, cannot be tolerated, or are contraindicated (Class I, Level C) | For NSTE-ACS or STEMI without fibrinolytic: loading 300 or 600 mg; maintenance 75 mg daily |
ESC 2023 also says prasugrel should be considered in preference to ticagrelor for ACS patients who proceed to PCI (Class IIa, Level B).[1] ACC/AHA 2025 says prasugrel should not be administered to patients with a history of stroke or transient ischaemic attack, because of worse net clinical outcomes (COR 3: Harm, LOE B-R).[2]
Who is at high bleeding risk?
Before you shorten anything, decide whether the patient is HBR.[1] ESC 2023 says HBR should be assessed in a structured manner, for example one major or two minor ARC-HBR characteristics, and puts the criteria in its Supplementary data.[1] ACC/AHA 2025 prints them.[2]
The Academic Research Consortium determined 20 correlates of bleeding and proposed a consensus-based definition of HBR: at least 1 major or 2 minor criteria at the time of PCI (ACC/AHA 2025).[2]
Academic Research Consortium High Bleeding Risk Criteria After PCI (ACC/AHA 2025, Table 22)
| Major criteria | Minor criteria |
|---|---|
| — | Age 75 years or more |
| Anticipated use of long-term oral anticoagulation | — |
| Severe or end-stage chronic kidney disease (CKD) (eGFR under 30 mL/min) | Moderate CKD (eGFR 30–59 mL/min) |
| Haemoglobin under 11 g/dL | Haemoglobin 11–12.9 g/dL for men and 11–11.9 g/dL for women |
| Spontaneous bleeding requiring hospitalisation or transfusion in the past 6 months, or at any time if recurrent | Spontaneous bleeding requiring hospitalisation or transfusion within the past 12 months not meeting the major criterion |
| Moderate or severe baseline thrombocytopenia (platelet count under 100 × 10⁹/L) | — |
| Chronic bleeding diathesis | — |
| Liver cirrhosis with portal hypertension | — |
| — | Long-term use of oral NSAIDs or steroids |
| Active malignancy (excluding non-melanoma skin cancer) within the past 12 months | — |
| Previous spontaneous intracranial haemorrhage (ICH) at any time; previous traumatic ICH within the past 12 months; presence of a brain arteriovenous malformation; moderate or severe ischaemic stroke within the past 6 months | Any ischaemic stroke at any time not meeting the major criterion |
| Non-deferrable major surgery on DAPT | — |
| Recent major surgery or major trauma within 30 days before PCI | — |
ACC/AHA 2025 adds under the table that the presence of at least 1 major or 2 minor criteria helps to identify those at increased risk of bleeding.[2]
[2] [1]What ESC 2023 prints about HBR
- Anaemia: according to the ARC-HBR, haemoglobin under 11 g/dL at the time of PCI is a major criterion, whereas haemoglobin between 11 and 13 g/dL (12 g/dL for women) is a minor criterion.[1]
- Thrombocytopenia: the ARC-HBR criteria define a platelet count under 100 000/μL as a major criterion; ESC 2023 says clinically relevant thrombocytopenia can be defined as a platelet count under 100 000/μL or a relative drop of 50% from baseline in the context of ACS.[1]
- Cancer: as per the ARC-HBR criteria, patients with active cancer diagnosed in the past 12 months are considered HBR.[1]
- PRECISE-DAPT: in its Figure 12 legend (antithrombotic regimens in patients with ACS and an indication for oral anticoagulation), ESC 2023 regards patients with a PRECISE-DAPT score of 25 or more as HBR, in addition to the ARC-HBR criteria.[1]
- Scores: ESC 2023 says major bleeding is associated with increased mortality in ACS and places detail on scores that may be considered for estimating bleeding risk in its Supplementary data, including Table S12.[1]
ACC/AHA 2025 ACS, AHA/ACC 2023 CCD, ESC 2024 CCS and NHFA/CSANZ 2025 each give bleeding-risk tools a place.[2][4][3][8] ACC/AHA 2025 says several tools predict ischaemic and/or bleeding risk and may be useful when considering how to personalise care for an individual patient.[2] AHA/ACC 2023 chronic coronary disease (CCD) says validated bleeding risk scores can be useful in the choice and duration of antiplatelet therapy, naming PRECISE-DAPT, DAPT and PARIS as the more frequently used.[4] ESC 2024 chronic coronary syndromes (CCS) defines bleeding risk by PRECISE-DAPT or ARC-HBR, with the criteria in its Supplementary Table S2.[3] In its Recommendation Table 26, ESC 2024 CCS recommends bleeding risk assessment using the PRECISE-DAPT score, the qualitative ARC-HBR tool or other, validated methods (Class I, Level B).[3]
Cutting the bleeding risk at the PCI itself
- Anticoagulant doses adjusted to body weight and renal function, especially in women and older patients.[1]
- Radial artery approach as default vascular access.[1]
- PPIs in patients on DAPT at higher-than-average risk of gastrointestinal bleeds: history of gastrointestinal ulcer or haemorrhage, anticoagulant therapy, chronic NSAID or corticosteroid use, or two or more of age 65 years or more, dyspepsia, gastro-oesophageal reflux disease, Helicobacter pylori infection and chronic alcohol use.[1]
- In patients on an OAC: PCI performed without interruption of vitamin K antagonists (VKAs) or NOACs; in patients on VKAs, no unfractionated heparin (UFH) if the INR is over 2.5; in patients on NOACs, low-dose parenteral anticoagulation is added regardless of the timing of the last NOAC dose (for example enoxaparin 0.5 mg/kg i.v. or UFH 60 IU/kg).[1]
- Aspirin is indicated, but pre-treatment with P2Y12 receptor inhibitors is avoided.[1]
- Glycoprotein IIb/IIIa receptor inhibitors only for bailout or peri-procedural complications.[1]
These are the ESC 2023 Table 7 suggested strategies to reduce bleeding risk related to PCI; the text introduces the table as strategies to minimise PCI-related complications in patients on an OAC.[1]
Duration after ACS: the default and the alternatives
Both ACS guidelines start from a year of DAPT: ESC 2023 for 12 months unless there is HBR, and ACC/AHA 2025 for at least 1 year in patients not at high bleeding risk.[1][2] ESC 2023 calls 12-month DAPT, preferably with prasugrel or ticagrelor, the default strategy for patients with ACS.[1] ACC/AHA 2025 says the default minimum of 1 year is most applicable to patients without HBR presenting with ACS.[2]
ESC 2023 divides the antiplatelet strategies to reduce bleeding risk in the first 12 months after an ACS into abbreviated DAPT strategies and DAPT de-escalation strategies.[1] ESC 2023 says they should be used only as alternatives to the default, in general driven by a motivation to reduce bleeding, for example in an HBR patient.[1] It chooses the specific strategy, including the P2Y12 inhibitor, DAPT duration and SAPT agent, by whether the patient is HBR.[1]
ESC 2023: alternative regimens in the first year
| ESC 2023 recommendation (Recommendation Table 6, shortening/de-escalation) | Class | Level |
|---|---|---|
| In patients who are event-free after 3–6 months of DAPT and who are not high ischaemic risk, SAPT (preferably with a P2Y12 receptor inhibitor) should be considered | IIa | A |
| De-escalation of P2Y12 receptor inhibitor treatment (for example a switch from prasugrel/ticagrelor to clopidogrel) may be considered as an alternative DAPT strategy to reduce bleeding risk | IIb | A |
| In HBR patients, aspirin or P2Y12 receptor inhibitor monotherapy after 1 month of DAPT may be considered | IIb | B |
| De-escalation of antiplatelet therapy in the first 30 days after an ACS event is not recommended | III | B |
ACC/AHA 2025: DAPT in the first 12 months after discharge
| ACC/AHA 2025 recommendation (DAPT strategies in the first 12 months postdischarge) | COR | LOE |
|---|---|---|
| In patients with ACS who are not at high bleeding risk, DAPT with aspirin and an oral P2Y12 inhibitor should be administered for at least 1 year to reduce MACE | 1 | A |
| In patients with ACS who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy 1 month or more after PCI is useful to reduce bleeding risk | 1 | A |
| In patients at high risk of gastrointestinal bleeding, a PPI is recommended in combination with DAPT, oral anticoagulants, or both to reduce risk of bleeding | 1 | A |
| In patients with ACS undergoing PCI, de-escalation of DAPT (switching from ticagrelor or prasugrel to clopidogrel) after 1 month may be reasonable to reduce bleeding risk | 2b | B-R |
| In patients with ACS undergoing PCI who are at high bleeding risk, transition to SAPT (aspirin or P2Y12 inhibitor) after 1 month may be reasonable to reduce bleeding risk | 2b | B-R |
Why the alternatives are not the default
- Powered for bleeding: ESC 2023 says much of the evidence comes from trials powered primarily for bleeding outcomes, many with a non-inferiority design, so they were not powered to detect potentially relevant differences in ischaemic outcomes.[1]
- Selected patients: the populations were often relatively selected, often excluding or under-representing the highest-risk ACS patients (ESC 2023).[1]
- So, in practice: ESC 2023 says these strategies should not be employed as a default in the wider ACS population, but can be considered when there is a specific motivation, such as reducing bleeding in HBR patients or other specific concerns about 12-month potent P2Y12 inhibitor-based DAPT.[1]
- Patients without PCI: ACC/AHA 2025 says the efficacy and safety of shorter DAPT strategies have not been rigorously studied in patients not undergoing PCI.[2]
Which drug to keep when you shorten
Keep ticagrelor
ACC/AHA 2025
- Several randomised trials consistently showed that aspirin withdrawal followed by ticagrelor monotherapy after 1 to 3 months of ticagrelor-based DAPT gave less bleeding without clear excess in MACE, compared with continued DAPT, in patients with ACS undergoing PCI
- COR 1, LOE A: in patients with ACS who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy 1 month or more after PCI is useful to reduce bleeding risk
Clopidogrel alone
ACC/AHA 2025
- Data have been mixed; concerns have been raised that clopidogrel monotherapy started 1 to 2 months after PCI may increase risk of MACE in ACS compared with longer DAPT
- It remains unknown whether this may be explained by excess thrombotic risk in patients with inadequate platelet inhibition to clopidogrel, observed in 30% to 40% of patients after PCI
Aspirin alone or prasugrel alone
ACC/AHA 2025
- A randomised trial showed that stopping the P2Y12 inhibitor and continuing aspirin alone after 6 months of DAPT resulted in excess thrombotic risk in ACS patients undergoing PCI (n = 2,712; 38% STEMI), albeit with less bleeding; similar findings were seen with discontinuation at 3 months
- The safety of prasugrel monotherapy has not been established in patients 1 month or more after ACS
The trials as ESC 2023 and ACC/AHA 2025 report them
- 12 months vs 6 months or less: ESC 2023 reports RCTs and meta-analyses of standard 12-month DAPT against 6 months or less followed by aspirin monotherapy in ACS; in some, less bleeding came at the cost of more ischaemic complications.[1]
- Network meta-analysis: ESC 2023 reports that 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or stent thrombosis in ACS patients.[1]
- 1–3 months then P2Y12 monotherapy: ESC 2023 reports large RCTs in patients with and without ACS that in general included low to intermediate ischaemic risk patients, using early clopidogrel or ticagrelor monotherapy; patients with STEMI tended to be excluded or under-represented.[1]
- TWILIGHT: ESC 2023 reports that this trial examined ticagrelor monotherapy against ticagrelor plus aspirin for 1 year after 3 months of DAPT (ticagrelor and aspirin), on clinically relevant bleeding; it enrolled ‘high-risk’ patients as per the trial inclusion criteria (at least one clinical feature and one angiographic feature associated with a high risk of ischaemic or bleeding events) who had not had a major bleeding or ischaemic event in the 3 months after hospital discharge; STEMI patients were excluded.[1]
- STOPDAPT-2-ACS: ESC 2023 reports that ACS patients were randomised at 1–2 months to clopidogrel monotherapy or continued DAPT for 12 months; non-inferiority for the composite of cardiovascular or bleeding events was not proven, suggesting that systematic very short DAPT (under 3 months) followed by clopidogrel monotherapy is not a useful strategy in ACS.[1]
- MASTER DAPT: ESC 2023 reports a trial in 4579 HBR patients (49% ACS, 12% STEMI) treated with a bioabsorbable polymer-coated stent, comparing 1 month of DAPT then aspirin or P2Y12 inhibitor monotherapy with DAPT for 3 months or more; net adverse clinical events and major adverse cardiac or cerebral events were comparable, and major or clinically relevant non-major bleeding was significantly reduced with abbreviated therapy.[1]
- MASTER DAPT, ACC/AHA view: ACC/AHA 2025 reports non-inferiority for composite ischaemic events and superiority for clinically relevant bleeding over 1 year with the abbreviated strategy, but says the trial was underpowered to judge whether to stop aspirin or the P2Y12 inhibitor.[2]
Switching between P2Y12 inhibitors
ESC 2023 says the need to switch between oral P2Y12 receptor inhibitors is not uncommon.[1] ESC 2023 lists bleeding complications or concern about bleeding, non-bleeding side effects such as dyspnoea on ticagrelor or allergic reactions, and socioeconomic factors.[1] It says switching between oral P2Y12 receptor inhibitors may be considered in selected cases.[1] When prasugrel or ticagrelor are not available, cannot be tolerated, or are contraindicated, ESC 2023 recommends clopidogrel (300–600 mg loading dose, 75 mg once daily maintenance) in Recommendation Table 5 (Class I, Level C).[1]
ESC 2023 prints its de-escalation rows among its alternative antithrombotic therapy regimens (Recommendation Table 6, under shortening/de-escalation).[1] The ESC 2023 text says de-escalation may be considered as an alternative to the default regimen to reduce bleeding, but warns of a potential risk of increased ischaemic events.[1] ESC 2023 does not recommend de-escalation of antiplatelet therapy in the first 30 days after an ACS event (Class III, Level B).[1]
- Guided de-escalation (ACC/AHA 2025): trials of guided de-escalation after PCI have shown either a lack of benefit, non-inferiority, or reductions in minor bleeding against conventional DAPT.[2]
- Unguided de-escalation (ACC/AHA 2025): randomised trials suggested that unguided de-escalation 1 month after PCI reduces bleeding without incurring ischaemic risk compared with longer-term prasugrel- or ticagrelor-based DAPT; trials of ticagrelor and prasugrel suggest the benefit of more potent therapy extends beyond the early phase, but with more bleeding.[2]
- TROPICAL-ACS (as ESC 2023 reports it): 44% NSTE-ACS and 56% STEMI; de-escalation from prasugrel to clopidogrel at 2 weeks after ACS, guided by platelet function testing, was non-inferior to standard prasugrel at 1 year after PCI for net clinical benefit.[1]
- POPular Genetics (as ESC 2023 reports it): in ACS patients undergoing primary PCI within the previous 48 h, de-escalation from ticagrelor or prasugrel to clopidogrel guided by CYP2C19 genotyping was non-inferior to standard treatment at 12 months for thrombotic events, with less bleeding.[1]
- TOPIC (as ESC 2023 reports it): a single-centre trial of unguided de-escalation in 645 ACS patients (60% NSTE-ACS, 40% STEMI) after 1 month of potent DAPT; net adverse clinical events and bleeding were reduced and ischaemic endpoints were unchanged.[1]
- TALOS-AMI (as ESC 2023 reports it): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial of unguided de-escalation from ticagrelor to clopidogrel after 1 month of DAPT in 2697 ACS patients (46% NSTEMI or unstable angina, 54% STEMI); it gave significant 12-month reductions in net adverse clinical events and bleeding, and ESC 2023 notes that it only included East Asian populations.[1]
Testing before switching is where the guidelines part company, partly because they speak about different patients.[3][8] ESC 2024 CCS says current evidence does not support routine genotype or platelet function testing in CCS.[3] It calls replacing aspirin plus clopidogrel with aspirin plus ticagrelor or prasugrel a reasonable option in high-risk PCI in known carriers of a CYP2C19 loss-of-function allele.[3] NHFA/CSANZ 2025 says to consider routine genotypic or platelet function guidance of P2Y12 therapy in people with NSTE-ACS (weak recommendation, moderate certainty).[8]
Beyond 12 months
Long-term antithrombotic rows (ESC 2023 Recommendation Table 6; ESC 2024 Recommendation Table 17; AHA/ACC 2023 CCD)
| Recommendation | Guideline | Class/COR | Level/LOE |
|---|---|---|---|
| Adding a second antithrombotic agent to aspirin for extended long-term secondary prevention should be considered in patients with high ischaemic risk and without HBR | ESC 2023 ACS | IIa | A |
| Adding a second antithrombotic agent to aspirin for extended long-term secondary prevention may be considered in patients with moderate ischaemic risk and without HBR | ESC 2023 ACS | IIb | A |
| P2Y12 inhibitor monotherapy may be considered as an alternative to aspirin monotherapy for long-term treatment | ESC 2023 ACS | IIb | A |
| In CCS patients with a prior MI or remote PCI, aspirin 75–100 mg daily is recommended lifelong after an initial period of DAPT | ESC 2024 CCS | I | A |
| In CCS patients with a prior MI or remote PCI, clopidogrel 75 mg daily is recommended as a safe and effective alternative to aspirin monotherapy | ESC 2024 CCS | I | A |
| Adding a second antithrombotic agent to aspirin for extended long-term secondary prevention should be considered in patients at enhanced ischaemic risk and without HBR | ESC 2024 CCS | IIa | A |
| In CCS or stabilised post-ACS patients who underwent PCI and were initially treated with ticagrelor-based DAPT, who remain at high ischaemic risk and are not at HBR, ticagrelor monotherapy 90 mg twice daily may be considered as an alternative to dual or other single antiplatelet therapy | ESC 2024 CCS | IIb | C |
| In patients with CCD who have had a previous MI and are at low bleeding risk, extended DAPT beyond 12 months for up to 3 years may be reasonable to reduce MACE | AHA/ACC 2023 CCD | 2b | A |
Of the two ESC documents in this table, ESC 2024 CCS is newer than ESC 2023 ACS.[3][1] Its long-term aspirin and clopidogrel rows shown above are written for CCS patients with a prior MI or remote PCI.[3] Its ticagrelor monotherapy row is for CCS or stabilised post-ACS patients who underwent PCI and were initially treated with ticagrelor-based DAPT, who remain at high ischaemic risk and are not at HBR.[3]
ESC 2023 adds a caution: the trials behind prolonged second-agent therapy ran for a mean of 23 months (COMPASS), a mean of 18 months (DAPT trial) and a median of 33 months (PEGASUS-TIMI 54).[1] Benefits and risks beyond those time points are at present unclear.[1] ESC 2024 CCS says that in high ischaemic risk CCS patients without HBR, aspirin plus ticagrelor 60 mg twice daily or aspirin plus rivaroxaban 2.5 mg twice daily should be considered, with regular re-evaluation of bleeding and ischaemic risk.[3] ACC/AHA 2025 says it may be reasonable to extend DAPT beyond 1 year in select patients who have tolerated it, after considering long-term bleeding and thrombosis risks.[2]
Elective PCI for chronic coronary syndrome
ESC 2024 CCS recommends DAPT with aspirin and clopidogrel for up to 6 months as the default after PCI-stenting in CCS patients with no indication for oral anticoagulation.[3] AHA/ACC 2023 CCD indicates DAPT with aspirin and clopidogrel for 6 months after PCI in CCD, followed by SAPT.[4] ESC 2024 CCS says DAPT with aspirin and clopidogrel after PCI for CCS is recommended to reduce the risk of stent thrombosis and MI compared with aspirin alone.[3] With few exceptions, it sees no reason to replace clopidogrel with ticagrelor.[3] It reports that in ALPHEUS (1883 patients followed for 30 days), ticagrelor did not significantly reduce PCI-related MI or major myocardial injury, and minor bleeding was significantly increased.[3]
DAPT after elective PCI (ESC 2024 Recommendation Table 17; AHA/ACC 2023 CCD)
| Recommendation | Guideline | Class/COR | Level/LOE |
|---|---|---|---|
| In CCS patients with no indication for oral anticoagulation, DAPT with aspirin 75–100 mg and clopidogrel 75 mg daily for up to 6 months is recommended as the default antithrombotic strategy after PCI-stenting | ESC 2024 CCS | I | A |
| In patients at HBR but not at high ischaemic risk, it is recommended to discontinue DAPT 1–3 months after PCI and to continue with SAPT | ESC 2024 CCS | I | A |
| Stopping DAPT 1–3 months after PCI-stenting may be considered in patients who are neither at HBR nor at high risk of ischaemic events | ESC 2024 CCS | IIb | B |
| In CCS patients undergoing high-thrombotic-risk stenting (for example complex left main stem, 2-stent bifurcation, suboptimal stenting result, prior stent thrombosis, previously known CYP2C19 *2/*3 polymorphisms), prasugrel or ticagrelor (in addition to aspirin) may be considered instead of clopidogrel for the first month, and up to 3–6 months | ESC 2024 CCS | IIb | C |
| In patients with CCD treated with PCI, DAPT with aspirin and clopidogrel for 6 months after PCI followed by SAPT is indicated to reduce MACE and bleeding events | AHA/ACC 2023 CCD | 1 | A |
| In select patients with CCD treated with PCI and a drug-eluting stent who have completed a 1- to 3-month course of DAPT, P2Y12 inhibitor monotherapy for at least 12 months is reasonable to reduce bleeding risk | AHA/ACC 2023 CCD | 2a | A |
- Why 1–3 months can be enough (ESC 2024 CCS): RCTs of 1 or 3 months of DAPT showed a decrease in mostly minor bleeding without more ischaemic events, indicating that 1–3 months may benefit CCS patients who are not at high ischaemic risk or who are at HBR.[3]
- MASTER DAPT, CCS view: ESC 2024 reports 4579 HBR PCI patients (about 50% CCS) randomised after 1 month of uneventful DAPT to immediate DAPT discontinuation or to DAPT continuation for at least 2 more months; after 335 days, discontinuation was non-inferior for ischaemic events compared with standard-duration DAPT, with less major and clinically relevant non-major bleeding.[3]
- HBR meta-analysis: ESC 2024 reports 11 RCTs and 9006 HBR patients (42% CCS), with HBR defined by a PRECISE-DAPT score above 25 or by ARC-HBR; 1–3 months of DAPT reduced major bleeding, ischaemic events and cardiovascular mortality at 12 months against standard DAPT, irrespective of CCS or ACS presentation.[3]
ESC 2024 CCS sums it up: in CCS patients with HBR, DAPT discontinuation 1–3 months after PCI is recommended; without HBR, the duration may be reduced only in the absence of high ischaemic risk.[3]
Gastric protection
On gastric protection the guidelines largely agree.[1][2][3] ESC 2023 says PPIs reduce the risk of upper gastroduodenal bleeding in patients treated with antiplatelet agents.[1] ACC/AHA 2025 says they reduce gastrointestinal bleeding in patients receiving aspirin, DAPT or an oral anticoagulant.[2]
PPI rows by guideline
| Recommendation | Guideline | Class/COR | Level/LOE |
|---|---|---|---|
| A PPI in combination with DAPT is recommended in patients at high risk of gastrointestinal bleeding | ESC 2023 ACS | I | A |
| In patients at high risk of gastrointestinal bleeding, a PPI is recommended in combination with DAPT, oral anticoagulants, or both to reduce risk of bleeding | ACC/AHA 2025 ACS | 1 | A |
| A PPI is recommended in patients at increased risk of gastrointestinal bleeding for the duration of combined antithrombotic therapy (antiplatelet therapy and/or OAC) | ESC 2024 CCS | I | A |
| A PPI should be considered when a single antithrombotic (antiplatelet or anticoagulant) drug is used, considering the gastrointestinal bleeding risk of the individual patient | ESC 2024 CCS | IIa | A |
| In patients with CCD on DAPT, the use of a PPI can be effective in reducing gastrointestinal bleeding risk | AHA/ACC 2023 CCD | 2a | B-R |
The clopidogrel–PPI question
- ESC 2023: PPIs that inhibit CYP2C19, particularly omeprazole and esomeprazole, may reduce the pharmacodynamic response to clopidogrel, though there is no strong evidence that this increases ischaemic events or stent thrombosis in clinical trials and propensity score-matched studies; no interaction with aspirin, prasugrel or ticagrelor has been observed.[1]
- ACC/AHA 2025: ex vivo studies found clopidogrel-induced platelet inhibition attenuated with certain PPIs, most pronounced with omeprazole; a double-blind, placebo-controlled randomised trial showed no significant difference in ischaemic events with omeprazole vs placebo in clopidogrel-treated patients, while PPI use markedly decreased gastrointestinal bleeding.[2]
- ACC/AHA 2025: the antiplatelet effects and clinical efficacy of ticagrelor and prasugrel are not appreciably modified with concomitant PPI use.[2]
- ESC 2024 CCS: omeprazole and esomeprazole inhibit CYP2C19 and reduce exposure to clopidogrel's active metabolite; their use with clopidogrel is discouraged, though univocal effects on ischaemic events or stent thrombosis have not been demonstrated.[3]
Triple therapy: antiplatelets with an oral anticoagulant
Picture the 74-year-old with permanent AF on apixaban who has just had a stent for NSTEMI.[1] ESC 2023 says long-term OAC is indicated in 6–8% of patients undergoing PCI and should be continued during the procedure.[1] ACC/AHA 2025 says bleeding risks are increased with the triple combination of aspirin, P2Y12 inhibitor and anticoagulant.[2]
- Re-check the indication (ESC 2023): in ACS, the indication for OAC should be re-assessed and treatment continued only if a compelling indication exists, such as AF with a CHA2DS2-VASc score of 1 or more in men and 2 or more in women, a mechanical heart valve, or recent or recurrent or unprovoked deep vein thrombosis or pulmonary embolism.[1]
- Choose a NOAC (ESC 2023): in AF without mechanical prosthetic valves or moderate to severe mitral stenosis, the evidence supports NOACs over VKAs because they reduce bleeding risk.[1]
- Choose clopidogrel (ACC/AHA 2025): trials of prasugrel and ticagrelor excluded patients requiring long-term anticoagulation, so clopidogrel is generally favoured for most patients.[2]
- NOAC doses (ESC 2023, Figure 12 legend): apixaban 5 mg twice daily, dabigatran 110 mg or 150 mg twice daily, edoxaban 60 mg once daily, rivaroxaban 15 mg or 20 mg once daily, with dose reductions by drug-specific criteria including renal function, body weight, concomitant medications and age.[1]
ESC 2023: ACS with an indication for oral anticoagulation
| ESC 2023 ACS recommendation (Recommendation Tables 5 and 6) | Class | Level |
|---|---|---|
| As the default for AF with CHA2DS2-VASc 1 or more in men and 2 or more in women: after up to 1 week of TAT following the ACS event, DAT with a NOAC at the stroke-prevention dose and a single oral antiplatelet agent (preferably clopidogrel) for up to 12 months | I | A |
| In patients treated with an OAC, aspirin plus clopidogrel for longer than 1 week and up to 1 month should be considered in those with high ischaemic risk or other anatomical/procedural characteristics judged to outweigh the bleeding risk | IIa | C |
| In patients requiring anticoagulation and treated medically, a single antiplatelet agent in addition to an OAC should be considered for up to 1 year | IIa | B |
| In patients requiring OAC, withdrawing antiplatelet therapy at 6 months while continuing OAC may be considered | IIb | B |
| Discontinuation of antiplatelet treatment in patients treated with an OAC is recommended after 12 months | I | B |
| The use of ticagrelor or prasugrel as part of triple antithrombotic therapy is not recommended | III | C |
| When rivaroxaban is used and concerns about HBR prevail over ischaemic stroke, rivaroxaban 15 mg once daily should be considered in preference to 20 mg once daily for the duration of concomitant SAPT or DAPT | IIa | B |
| In patients at HBR, dabigatran 110 mg twice daily should be considered in preference to 150 mg twice daily for the duration of concomitant SAPT or DAPT, to mitigate bleeding risk | IIa | B |
| With VKA plus aspirin and/or clopidogrel, careful regulation of VKA dose intensity with a target INR of 2.0–2.5 and time in therapeutic range over 70% should be considered | IIa | B |
| During PCI, a UFH bolus is recommended if the patient is on a NOAC, or if the INR is under 2.5 in VKA-treated patients | I | C |
For patients with AF, ESC 2024 AF is newer than ESC 2023 ACS, and it splits the rows by setting.[5][1] Its ACS row adds conditions the 2023 default row does not carry: an uncomplicated PCI, and a low thrombosis risk or a high bleeding risk.[5][1]
ESC 2024 AF: patients with ACS or undergoing PCI
| ESC 2024 AF recommendation (Recommendation Table 24) | Class | Level |
|---|---|---|
| For combinations with antiplatelet therapy, a DOAC is recommended in eligible patients in preference to a VKA, to mitigate bleeding risk and prevent thromboembolism | I | A |
| AF with ACS: early cessation (1 week or less) of aspirin and continuation of an OAC (preferably DOAC) with a P2Y12 inhibitor (preferably clopidogrel) for up to 12 months is recommended in patients undergoing an uncomplicated PCI, to avoid major bleeding, if the risk of thrombosis is low or bleeding risk is high | I | A |
| AF with ACS: triple therapy with aspirin, clopidogrel and OAC for longer than 1 week should be considered when ischaemic risk outweighs bleeding risk, with the total duration (1 month or less) decided by assessment of these risks and clear documentation of the discharge plan | IIa | C |
| AF undergoing PCI: after uncomplicated PCI, early cessation (1 week or less) of aspirin and continuation of an OAC and a P2Y12 inhibitor (preferably clopidogrel) for up to 6 months is recommended to avoid major bleeding, if ischaemic risk is low | I | A |
| AF undergoing PCI: triple therapy with aspirin, clopidogrel and an OAC for longer than 1 week should be considered when the risk of stent thrombosis outweighs the bleeding risk, with the total duration (1 month or less) decided by assessment of these risks and clear documentation | IIa | B |
| Antiplatelet therapy beyond 12 months is not recommended in stable patients with chronic coronary or vascular disease treated with OAC, due to lack of efficacy and to avoid major bleeding | III | B |
| Rivaroxaban 15 mg once daily should be considered in preference to 20 mg once daily, and dabigatran 110 mg twice daily in preference to 150 mg twice daily, when combined with antiplatelet therapy where concerns about bleeding risk prevail over concerns about stent thrombosis or ischaemic stroke | IIa | B |
| Carefully regulated VKA dosing with a target INR of 2.0–2.5 and time in therapeutic range over 70% should be considered when combined with antiplatelet therapy in AF patients, to mitigate bleeding risk | IIa | C |
- Peri-procedural triple therapy (ESC 2024 AF): a peri-procedural triple regimen of an OAC, aspirin and a P2Y12 inhibitor should be the default strategy for most patients with ACS treated by PCI.[5]
- Short triple therapy (ESC 2024 AF): triple therapy for 1 week or less is recommended for all patients without diabetes after ACS or PCI.[5]
- Prolonged triple therapy (ESC 2024 AF): up to 1 month after ACS/PCI should be considered at high ischaemic risk, for example STEMI, prior stent thrombosis, complex coronary procedures and prolonged cardiac instability, even though these patients were not adequately represented in the RCTs available so far.[5]
- Diabetes (ESC 2024 AF): in patients with ACS or CCS and diabetes undergoing coronary stenting, prolonging triple therapy with low-dose aspirin, clopidogrel and an OAC up to 3 months may be of benefit if thrombotic risk outweighs bleeding risk in the individual patient.[5]
- Clopidogrel (ESC 2024 AF): the preferred P2Y12 inhibitor, as the evidence for ticagrelor and prasugrel is less clear, with higher bleeding risk.[5]
Chronic coronary syndrome with an OAC indication
CCS and CCD rows with an OAC (ESC 2024 Recommendation Table 17; AHA/ACC 2023 CCD)
| Recommendation | Guideline | Class/COR | Level/LOE |
|---|---|---|---|
| In patients with an indication for OAC who undergo PCI, initial low-dose aspirin once daily is recommended (loading dose when not on maintenance dose) in addition to OAC and clopidogrel | ESC 2024 CCS | I | C |
| After uncomplicated PCI with a concomitant OAC indication: early cessation of aspirin (1 week or less), then OAC and clopidogrel up to 6 months if not at high ischaemic risk or up to 12 months if at high ischaemic risk, then OAC alone | ESC 2024 CCS | I | A |
| Continuation of aspirin up to 1 month after PCI, in addition to OAC and clopidogrel, should be considered at high ischaemic risk or with anatomical/procedural characteristics judged to outweigh the bleeding risk | ESC 2024 CCS | IIa | B |
| The use of ticagrelor or prasugrel is generally not recommended as part of triple antithrombotic therapy with aspirin and an OAC | ESC 2024 CCS | III | C |
| In CCS patients with a long-term indication for OAC, an AF therapeutic dose of VKA alone or, preferably, of DOAC alone (unless contraindicated) is recommended lifelong | ESC 2024 CCS | I | B |
| In patients with CCD who have undergone elective PCI and require oral anticoagulant therapy, DAPT for 1 to 4 weeks followed by clopidogrel alone for 6 months should be administered in addition to a DOAC | AHA/ACC 2023 CCD | 1 | B-R |
| In patients with CCD who have undergone PCI and require oral anticoagulant therapy, continuing aspirin in addition to clopidogrel for up to 1 month is reasonable if the patient has a high thrombotic risk and low bleeding risk | AHA/ACC 2023 CCD | 2a | B-R |
| In patients with CCD who require oral anticoagulation and have a low atherothrombotic risk, stopping aspirin and continuing a DOAC alone may be considered 1 year after PCI to reduce bleeding risk | AHA/ACC 2023 CCD | 2b | B-R |
The North American and Australian rows
- ACC/AHA 2025 ACS (COR 1, LOE B-R): in patients with ACS who require oral anticoagulant therapy, aspirin should be discontinued after 1 to 4 weeks of triple antithrombotic therapy, with continued use of a P2Y12 inhibitor (preferably clopidogrel) and an oral anticoagulant to reduce bleeding risk.[2]
- ACC/AHA 2025 synopsis and supportive text: for most patients, a DOAC will be preferred over a VKA; aspirin for up to 30 days after PCI could be considered with a high risk of stent thrombosis; the P2Y12 inhibitor should be continued for at least 12 months after PCI once aspirin stops, but could be stopped earlier with multiple risk factors for bleeding.[2]
- ACC/AHA 2023 AF (COR 1, LOE A): in AF with increased stroke risk undergoing PCI, DOACs are preferred over VKAs in combination with antiplatelet therapy; in most AF patients taking OAC who undergo PCI, early discontinuation of aspirin (1–4 weeks) with dual therapy of OAC and a P2Y12 inhibitor is preferred over triple therapy, to reduce clinically relevant bleeding.[6]
- ACC/AHA 2023 AF (COR 1, LOE B-R): in AF with CCD beyond 1 year after revascularisation, or CAD not requiring revascularisation, without a history of stent thrombosis, OAC monotherapy is recommended over OAC plus single antiplatelet therapy, to decrease major bleeding.[6]
- Which US row for which patient: ACC/AHA 2025 ACS gives its row for patients with ACS who require oral anticoagulant therapy; ACC/AHA 2023 AF gives its PCI rows for AF patients with an increased risk for stroke who undergo PCI and for most AF patients who take oral anticoagulation and undergo PCI, and its CCD row for AF with CCD (beyond 1 year after revascularisation, or CAD not requiring revascularisation) without a history of stent thrombosis; the AHA/ACC 2023 CCD rows with an OAC above are for patients with CCD who require oral anticoagulant therapy, the first after elective PCI, the second after PCI if the patient has a high thrombotic risk and low bleeding risk, and the third with a low atherothrombotic risk, 1 year after PCI.[2][6][4]
- NHFA/CSANZ 2025 (strong, high certainty): in people with ACS and non-valvular AF with a CHA2DS2-VA score above 1, give aspirin and clopidogrel together with a NOAC.[8]
- NHFA/CSANZ 2025 after discharge: with a long-term OAC indication, continue OAC and DAPT (preferentially aspirin and clopidogrel) for 1–4 weeks, then cease aspirin (strong, high certainty); cease antiplatelet therapy at 6–12 months and continue anticoagulation alone (strong, moderate certainty).[8]
Evidence behind the rows
- Subgroups: ESC 2023 says the evidence for ACS patients on long-term OAC undergoing PCI comes from subgroups of RCTs, and STEMI patients, who generally carry a higher atherothrombotic risk, were under-represented (about 10% of study populations).[1]
- Meta-analysis of four NOAC trials (as ESC 2023 reports it): in 10 234 AF patients undergoing PCI, DAT lowered International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding against TAT (RR 0.66, 95% CI 0.56–0.78).[1]
- The price (ESC 2023): no significant differences in death, stroke or MACE, but DAT was associated with a borderline increased risk of MI (RR 1.22) and a significant increase in stent thrombosis (RR 1.59): an absolute 2.3% reduction in major bleeding against an absolute 0.4% increase in stent thrombosis.[1]
- A confounder (ESC 2023): the treatment effect is confounded by NOACs in the DAT arms and VKAs in the TAT arms.[1]
- AUGUSTUS secondary analyses (as ESC 2023 reports them): AUGUSTUS was an open-label, 2 × 2 factorial, randomised controlled trial of apixaban versus VKA and aspirin versus aspirin placebo in patients with AF and ACS or PCI. Stent thrombosis was highest within the first 30 days after randomisation, with higher rates without aspirin. Aspirin reduced ischaemic events but increased major bleeding in the first 30 days; after 30 days and up to 6 months it did not affect ischaemic events but increased bleeding.[1]
- AFIRE (as ESC 2023 reports it): 2236 AF patients with PCI or CABG more than 1 year earlier, or documented CAD, were randomised to rivaroxaban alone or rivaroxaban plus a single antiplatelet agent; monotherapy was non-inferior for the efficacy composite and superior for major bleeding.[1]
- Potent agents as DAT (ESC 2023): evidence is limited; ticagrelor was used in 5–12% and prasugrel in 1–2% of patients in the four pivotal RCTs.[1]
ESC 2023 says DAT may be shortened to 6 months by withdrawing the antiplatelet in certain patients, for example those with multiple HBR factors.[1] In medically managed ACS, current data support DAT over TAT, with a single antiplatelet agent (most commonly clopidogrel) for at least 6 months.[1] Where a VKA is mandated, for example with a mechanical prosthetic valve, ESC 2023 says DAT with a VKA and SAPT (preferably clopidogrel) is indicated after up to 1 week of TAT with aspirin and clopidogrel.[1]
When the patient bleeds
Here the held guideline text is thinner than you might expect.[1] ESC 2023 refers the management of bleeding to its Supplementary data (Section 12.1.3.1).[1] What the held text does give is guidance on transfusion, on platelets around surgery, and on the alternative regimens that may be considered in patients at high bleeding risk.[1][2][7]
Red cell transfusion: the two guidelines disagree
ESC 2023
no formal recommendation
- Liberal transfusion has usually been defined as transfusion at haemoglobin under 9–10 g/dL and restrictive transfusion as transfusion at haemoglobin under 7–8 g/dL
- REALITY, an open-label trial as ESC 2023 reports it: 668 ACS patients randomised to restrictive (haemoglobin 8 or less) or liberal (haemoglobin 10 or less) transfusion; the 30-day composite was comparable (11% vs 14%), meeting non-inferiority
- At 1 year the restrictive strategy did not achieve non-inferiority for MACE, so ESC 2023 says no formal recommendation on liberal versus restrictive transfusion in ACS can be made at present
ACC/AHA 2025
COR 2b, LOE B-R
- In patients with ACS and acute or chronic anaemia, blood transfusion to achieve a haemoglobin level of 10 g/dL or more may be reasonable to reduce cardiovascular events
- MINT, as ACC/AHA 2025 reports it, randomly assigned 3,504 patients with STEMI or NSTEMI and haemoglobin under 10 g/dL (13% with recent bleeding) to restrictive (under 7–8 g/dL) or liberal (under 10 g/dL) transfusion; patients with uncontrolled bleeding, on palliative treatment or scheduled for cardiac surgery were ineligible
- 30-day death or recurrent MI: 16.9% restrictive vs 14.5% liberal (RR 1.15, 95% CI 0.99–1.34); cardiac death 5.5% vs 3.2% (RR 1.74, 95% CI 1.26–2.40)
ACC/AHA 2025 notes that anaemia predicts worse outcomes whether it is chronic from comorbid conditions or acute from bleeding related to antithrombotic therapy or invasive procedures.[2]
Platelets and reversal around surgery
- Platelet transfusion (ESC 2022 NCS): for patients on antiplatelet therapy with excessive or life-threatening peri-operative bleeding, platelet transfusion is recommended as a bail-out strategy.[7]
- Ticagrelor (ESC 2022 NCS): ticagrelor and its active metabolite may also inhibit aggregation of transfused platelets; experimental data indicate albumin binds ticagrelor and reduces its inhibitory effect, and ESC 2022 described a monoclonal antibody fragment (PB2452) to neutralise ticagrelor as in development but not yet clinically available.[7]
- Platelet function tests (ESC 2022 NCS): neither the optimal assay nor a universal cut-off value associated with bleeding has been defined and validated in NCS.[7]
High bleeding risk: rows and related text
- ESC 2023: in HBR patients, aspirin or P2Y12 receptor inhibitor monotherapy after 1 month of DAPT may be considered (Class IIb, Level B).[1]
- ACC/AHA 2025: in patients with ACS undergoing PCI who are at high bleeding risk, transition to SAPT (aspirin or P2Y12 inhibitor) after 1 month may be reasonable to reduce bleeding risk (COR 2b, LOE B-R).[2]
- ESC 2023 lists bleeding complications, or concern about bleeding, among the reasons for switching between P2Y12 inhibitors.[1]
- In the ARC-HBR criteria printed in ACC/AHA 2025 Table 22, spontaneous bleeding requiring hospitalisation or transfusion in the past 6 months, or at any time if recurrent, is a major criterion; within the past 12 months and not meeting the major criterion, it is a minor criterion.[2]
- AHA/ACC 2023 CCD: chronic NSAIDs should not be used in CCD because of increased cardiovascular and bleeding complications (COR 3: Harm, LOE B-R).[4]
Surgery on DAPT
Cardiac surgery (CABG)
Management of Oral P2Y12 Inhibitors for Patients Who Require CABG Surgery (ACC/AHA 2025, Table 8)
| P2Y12 inhibitor | Elective CABG | Urgent CABG |
|---|---|---|
| Clopidogrel | Interrupt for 5 days before surgery | Interruption for at least 24 h (ideally); proceeding earlier than 5 days may be reasonable |
| Prasugrel | Interrupt for 7 days before surgery | Interruption for at least 24 h (ideally); proceeding earlier than 7 days may be reasonable |
| Ticagrelor | Interrupt for 3–5 days before surgery | Interruption for at least 24 h (ideally); proceeding earlier than 5 days may be reasonable |
- Restart (ACC/AHA 2025, Table 8 footnote): for all patients, the oral P2Y12 inhibitor should be resumed after surgery when bleeding risk is not excessive (typically 24–72 hours).[2]
- After ACS (ESC 2023, Class I, Level C): if patients presenting with ACS stop DAPT to undergo CABG, it is recommended they resume DAPT after surgery for at least 12 months.[1]
- Aspirin and stop intervals (ESC 2024 CCS): aspirin should be continued until the day of CABG and restarted as soon as there is no concern over bleeding, possibly within 24 h; in general, other antithrombotic drugs should be stopped at intervals related to their duration of action (prasugrel 7 days or more, clopidogrel 5 days or more, ticagrelor 3 days or more, and rivaroxaban, apixaban, edoxaban and dabigatran 1–2 days, depending on drug and renal function).[3]
- ESC 2024 CCS rows: after CABG, aspirin 75–100 mg daily is recommended lifelong (Class I, Level A); it is recommended to initiate aspirin post-operatively as soon as there is no concern over bleeding (Class I, Level B); DAPT may be considered after CABG in selected patients at greater risk of graft occlusion and at low risk of bleeding (Class IIb, Level B).[3]
- On an OAC (ESC 2023): in ACS patients undergoing CABG with an established OAC indication, anticoagulation with SAPT should be resumed after CABG as soon as possible and TAT should be avoided.[1]
Non-cardiac surgery after a stent
The surgical team will ask two questions: when can we operate, and what do we stop? ESC 2022 says the frequency of major NCS in the first year after PCI is about 4%, most frequently orthopaedic, abdominal and vascular surgery.[7] Observational studies report MACE in 2–8% of PCI patients undergoing NCS, a more than two-fold increase compared with non-stented patients.[7]
- Risk factors for MACE after NCS (ESC 2022): time from PCI to surgery, with the highest risk in the first month; primary PCI for STEMI; DAPT interruption or discontinuation; lesion characteristics including ostial and distal lesions; and urgency of surgery.[7]
- Stent thrombosis (ESC 2022): its prognosis appears worse than that of de novo coronary occlusion, and premature interruption of DAPT after recent stenting is the strongest predictor of stent thrombosis.[7]
- High risk of peri-operative stent thrombosis (ESC 2022, Figure 5 legend): at least one of history of stent thrombosis under antiplatelet therapy, LVEF under 40%, poorly controlled diabetes, severely impaired renal function or haemodialysis, recent complex PCI (severely calcified lesion, left main PCI, chronic total occlusion, bifurcational/crush technique, bypass graft PCI), or stent malapposition or residual dissection.[7]
Recommendations for use of antiplatelet therapy in patients undergoing non-cardiac surgery (ESC 2022, all rows)
| ESC 2022 NCS recommendation (Recommendation Table 13) | Class | Level |
|---|---|---|
| Delay elective NCS until 6 months after elective PCI and 12 months after an ACS | I | A |
| After elective PCI, delay time-sensitive NCS until a minimum of 1 month of DAPT has been given | I | B |
| With a recent PCI scheduled for NCS, management of antiplatelet therapy should be discussed between the surgeon, anaesthesiologist and cardiologist (recommended) | I | C |
| In high-risk patients with a recent PCI (for example STEMI or high-risk NSTE-ACS), a DAPT duration of at least 3 months should be considered before time-sensitive NCS | IIa | C |
| With a previous PCI, continue aspirin peri-operatively if the bleeding risk allows (recommended) | I | B |
| If interruption of a P2Y12 inhibitor is indicated, withhold ticagrelor for 3–5 days, clopidogrel for 5 days and prasugrel for 7 days before NCS (recommended) | I | B |
| For high bleeding risk surgery (for example intracranial, spinal neurosurgery or vitreoretinal eye surgery), interrupt aspirin for at least 7 days pre-operatively (recommended) | I | C |
| Without a history of PCI, interruption of aspirin at least 3 days before NCS may be considered if the bleeding risk outweighs the ischaemic risk, to reduce the risk of bleeding | IIb | B |
| If antiplatelet therapy has been interrupted, restart it as soon as possible (within 48 h) after surgery, according to interdisciplinary risk assessment (recommended) | I | C |
The narrative fills in the reasoning behind the rows.[7] ESC 2022 says the preferred management is to delay elective NCS until the full course of DAPT is complete: 6 months after elective PCI and 12 months after ACS.[7] ESC 2022 bases the 1-month floor for time-sensitive surgery on recent trials in which 1–3 months of DAPT after modern drug-eluting stents was associated with acceptable rates of MACE and stent thrombosis in low- and moderate-risk patients.[7] Once the P2Y12 inhibitor has been stopped, surgery should be performed while the patient is still on aspirin.[7]
- Cannot wait, cannot stop (ESC 2022): when time-sensitive surgery cannot be postponed and cannot be done on the recommended DAPT, de-escalation or shortening of DAPT is recommended; this may encompass switching prasugrel or ticagrelor to clopidogrel, or stopping aspirin and using prasugrel or ticagrelor monotherapy; if neither option is deemed sufficient, premature P2Y12 discontinuation may be considered.[7]
- Aspirin as the last thing to stop (ESC 2022): whenever possible in patients with a DAPT indication, surgery should be performed without stopping aspirin; aspirin might be discontinued as a last measure only with very high bleeding risk and comparably low ischaemic risk, in hospitals with 24/7 catheterisation laboratories.[7]
- Why keep aspirin (ESC 2022): POISE-2 randomised 10 010 patients undergoing NCS with established cardiovascular disease, or at increased cardiovascular risk, to peri-operative aspirin or placebo; in its post hoc analysis of 470 patients (under 5%) with previous PCI, aspirin use was associated with fewer deaths or MIs (HR 0.50) without a significant increase in major or life-threatening bleeding; among patients with previous PCI, in the absence of very high bleeding risk, low-dose aspirin should be continued peri-operatively.[7]
- Clopidogrel off for 5 days (ESC 2022): a meta-analysis of observational data indicated that stopping clopidogrel for at least 5 days reduced re-operation for major bleeding by 50%, without more MACE or death.[7]
- Bridging (ESC 2022): although generally not recommended, bridging with i.v. eptifibatide, tirofiban or cangrelor might be applicable in rare cases when DAPT cannot be interrupted, for example very high risk of stent thrombosis, recurrent MI or recent PCI.[7]
- Bridging doses (ESC 2022, Figure 7 legend, includes): tirofiban 0.1 µg/kg/min, adjusted to 0.05 µg/kg/min if creatinine clearance is under 50 mL/min; cangrelor started within 72 h of P2Y12 inhibitor discontinuation at 0.75 μg/kg/min for a minimum of 48 h and a maximum of 7 days.[7]
- 24-hour catheter laboratory (ESC 2022, Figure 6 legend): suggested for major surgery within 6 months in non-ACS/non-high-risk patients and within 12 months in ACS/high-risk patients.[7]
- Long-term DAPT for other indications (ESC 2022): when NCS is required, discontinuation of P2Y12 inhibitors is recommended for 3–7 days, depending on the P2Y12 inhibitor.[7]
- P2Y12 monotherapy (ESC 2022): patients on P2Y12 inhibitor monotherapy (as part of de-escalation after PCI or ACS, or for a recent stroke, PAD or aspirin intolerance) may need peri-operative management of it; ESC 2022 calls for careful interdisciplinary evaluation of peri-operative bleeding versus ischaemic risk, and says individual decisions based on that peri-operative bleeding and ischaemic risk, for example surgery on monotherapy, switching to aspirin, short interruption or bridging, may be applicable, although evidence for these regimens is missing.[7]
- Monotherapy and haemostasis (ESC 2022): the effects of ticagrelor or clopidogrel monotherapy on haemostasis are considerably less than when they are combined with aspirin.[7]
- On an OAC as well (ESC 2022): elective surgery should be postponed until antiplatelet therapy can be safely stopped within combination therapy (6 months after elective PCI or 12 months after ACS).[7]
Surgical bleeding risk is part of the decision.[7] ESC 2022 Table 9 lists, among high bleeding risk surgery, neuraxial (spinal or epidural) anaesthesia, neurosurgery, major orthopaedic surgery, extensive cancer surgery, thoracic, urological and vascular surgery.[7] Among minor bleeding risk surgery it lists cataract or glaucoma procedures, dental extractions of 1–3 teeth, endoscopy without biopsy or resection and superficial surgery.[7] The American perioperative guideline (AHA/ACC 2026) is not held as text for this topic, so no US non-cardiac surgery rows are given here.
Special populations
- Older patients (ESC 2023, Class IIb, Level B): in older ACS patients, especially if HBR, clopidogrel as the P2Y12 receptor inhibitor may be considered; the definition of older varies across trials from 70 to 80 years, and frailty and comorbidities should also be considered.[1]
- Older adults (ESC 2023, Class I, Level B): it is recommended to adapt the choice and dosage of antithrombotic agent, and of secondary prevention medications, to renal function, co-medications, comorbidities, frailty, cognitive function and specific contraindications.[1]
- Low body weight or age 75 or more: ESC 2023 gives prasugrel 5 mg once daily for patients aged 75 years or more or weighing under 60 kg; ACC/AHA 2025 says dose reduction of prasugrel should be considered in these patients.[1][2]
- Prior stroke or TIA: prasugrel should not be administered because of worse net clinical outcomes (ACC/AHA 2025, COR 3: Harm, LOE B-R); in CCD with previous stroke, TIA or ICH, prasugrel should not be used because of the risk of significant or fatal bleeding (AHA/ACC 2023, COR 3: Harm, LOE B-R).[2][4]
- Cancer (ESC 2023): because these patients are considered HBR, clopidogrel is the preferred P2Y12 inhibitor in ACS with active cancer; potential drug–drug interactions with cancer therapies should be checked when using ticagrelor or clopidogrel, since some CYP450-based interactions may occur.[1]
- Cancer with low platelets (ESC 2023, all Class III, Level C): aspirin not recommended below 10 000/μL; clopidogrel not recommended below 30 000/μL; prasugrel or ticagrelor not recommended below 50 000/μL.[1]
- Women: the ARC-HBR minor anaemia threshold is lower for women (ACC/AHA 2025: 11–11.9 g/dL; ESC 2023: 11–12 g/dL), and ESC 2023 Table 7 lists anticoagulant doses adjusted to body weight and renal function, especially in women and older patients, among its suggested strategies to reduce bleeding risk related to PCI.[2][1]
- Pregnancy (ESC 2025 pregnancy, Recommendation Table 12): if DAPT is required, clopidogrel is recommended as the P2Y12 inhibitor of choice during pregnancy (Class I, Level C), and low-dose aspirin is recommended as the antiplatelet treatment of choice during pregnancy and lactation when single antiplatelet treatment is indicated (Class I, Level B).[9]
- DAPT duration in pregnancy (ESC 2025 pregnancy): in pregnant women undergoing coronary stent implantation, the duration of DAPT (aspirin and clopidogrel) is recommended to be the same as in non-pregnant women, with an individual approach considering ischaemic risk and delivery-related bleeding risks (Class I, Level C).[9]
- Medically managed ACS on an OAC: ESC 2023 says a single antiplatelet agent with an OAC should be considered for up to 1 year (Class IIa, Level B); ESC 2024 AF says 6 to 12 months of a single antiplatelet with a long-term DOAC is usually sufficient, and studies have typically used clopidogrel.[1][5]
- East Asian data: ACC/AHA 2025 says low-dose prasugrel monotherapy (3.75 mg daily) in Japanese patients very early after PCI with ACS or at high bleeding risk may increase 30-day MACE compared with DAPT.[2]
Evidence, guidelines and regional differences
Same question, three guidelines
| Question | ESC | ACC/AHA | NHFA/CSANZ 2025 |
|---|---|---|---|
| Default duration after ACS | 12 months unless HBR (2023 ACS, Class I, Level A) | At least 1 year if not at high bleeding risk (2025 ACS, COR 1, LOE A) | High ischaemic and/or low bleeding risk: DAPT for 6–12 months (strong, high certainty) |
| HBR or low ischaemic risk | HBR: aspirin or P2Y12 inhibitor monotherapy after 1 month of DAPT may be considered (2023 ACS, IIb, B) | HBR undergoing PCI: SAPT after 1 month may be reasonable (2025 ACS, 2b, B-R) | Low ischaemic and/or high bleeding risk: cease DAPT at 1–3 months and continue SAPT (strong, high certainty) |
| De-escalation | May be considered (2023 ACS, IIb, A); not in the first 30 days (III, B) | After 1 month in ACS undergoing PCI, may be reasonable (2025 ACS, 2b, B-R) | NSTE-ACS: consider, but not during the first 30 days (weak, moderate certainty) |
| SAPT after DAPT | P2Y12 inhibitor monotherapy may be considered as an alternative to aspirin long term (2023 ACS, IIb, A) | Transition to ticagrelor monotherapy 1 month or more after PCI, after tolerated ticagrelor DAPT, is useful to reduce bleeding risk (2025 ACS, COR 1, LOE A) | Long-term P2Y12 inhibitor over aspirin after a course of DAPT (strong, moderate certainty) |
| Aspirin with an OAC | Up to 1 week of TAT in the 2023 ACS default for AF with a CHA2DS2-VASc score of 1 or more in men and 2 or more in women (I, A); in AF with ACS and uncomplicated PCI, early cessation (1 week or less) if the risk of thrombosis is low or bleeding risk is high (2024 AF, I, A) | Stop aspirin after 1 to 4 weeks of TAT (2025 ACS, COR 1, LOE B-R) | Continue OAC and DAPT for 1–4 weeks, then cease aspirin (strong, high certainty) |
Each region is stated with its own body and year; none of these rows is a blend. The Australian rows carry a GRADE strength of recommendation and a certainty of evidence instead of a class.[8]
ANZ practice
The 2025 NHFA/CSANZ ACS guideline is quoted here through its Medical Journal of Australia summary.[8] Its decision tree for DAPT duration notes that prasugrel is not indicated in people who do not undergo PCI.[8] It also notes that current Pharmaceutical Benefits Scheme criteria preclude prescribing ticagrelor as single therapy.[8]
NHFA/CSANZ 2025 rows not shown above (Tables 3 and 4)
| NHFA/CSANZ 2025 recommendation | Strength | Certainty |
|---|---|---|
| In people with ACS undergoing coronary angiography, consider using bleeding risk scores to determine short-term bleeding risk | Weak | Moderate |
| In people with STEMI/ACOMI undergoing primary PCI and people with NSTE-ACS undergoing a routine invasive strategy, give DAPT with aspirin and a potent P2Y12 inhibitor (ticagrelor or prasugrel) | Strong | High |
| In people with STEMI/ACOMI undergoing primary PCI and people with NSTE-ACS undergoing a routine invasive strategy for whom ticagrelor or prasugrel are contraindicated, and those receiving oral anticoagulation, give clopidogrel | Strong | High |
| In people discharged after ACS who remain at high ischaemic and low bleeding risk, consider long-term DAPT (over 12 months) | Weak | Moderate |
| In people discharged after ACS with an indication for long-term OAC, cease antiplatelet therapy at 6–12 months and continue anticoagulation alone | Strong | Moderate |
Its figure on DOAC-treated AF prefers aspirin plus clopidogrel for DAPT and clopidogrel for SAPT, and says people receiving triple therapy should be given a PPI.[8]
Guidelines checked
A row called the newest, or the one covering a group, is so among the guidelines checked for this topic:
- Sources of the rows and statements used: ESC acute coronary syndromes (2023); ACC/AHA acute coronary syndromes (2025); ESC chronic coronary syndromes (2024); AHA/ACC chronic coronary disease (2023); ESC atrial fibrillation (2024); ACC/AHA atrial fibrillation (2023); ESC non-cardiac surgery (2022); NHFA/CSANZ acute coronary syndromes (2025, Medical Journal of Australia summary); ESC cardiovascular disease and pregnancy (2025).[1][2][3][4][5][6][7][8][9]
- Also swept for newer rows (the guidelines checked for this topic): ESC 2024 hypertension and peripheral arterial and aortic diseases; ESC/EAS 2025 dyslipidaemia; ESC 2025 valvular disease and myocarditis and pericarditis; ESC 2026 heart failure and cardiac rehabilitation; AHA/ACC 2025 blood pressure and 2026 pulmonary embolism; ACC/AHA 2026 dyslipidaemia; the Fifth Universal Definition of MI (2026).
- Not held as text for this topic: the AHA/ACC 2026 perioperative guideline for non-cardiac surgery; the ESC 2026 cardiovascular disease and chronic kidney disease guideline; the ESC 2023 diabetes guideline; the AHA/ACC 2026 cardiovascular-kidney-metabolic guideline.
Exam pearls
- ESC 2023: no de-escalation of antiplatelet therapy in the first 30 days after ACS (Class III, Level B).[1]
- ESC 2023: ticagrelor or prasugrel as part of triple antithrombotic therapy is not recommended (Class III, Level C); ESC 2024 CCS: generally not recommended (Class III, Level C).[1][3]
- ARC-HBR criteria after PCI (ACC/AHA 2025, Table 22): the presence of at least 1 major or 2 minor criteria helps to identify those at increased risk of bleeding; in its Figure 12 legend (ACS with an indication for oral anticoagulation), ESC 2023 also regards a PRECISE-DAPT score of 25 or more as HBR.[2][1]
- ESC 2022 NCS: withhold ticagrelor 3–5 days, clopidogrel 5 days, prasugrel 7 days if P2Y12 interruption is indicated (Class I, Level B), and, if antiplatelet therapy was interrupted, restart it as soon as possible (within 48 h) after surgery, according to interdisciplinary risk assessment (Class I, Level C).[7]
- ESC 2022 NCS: after elective PCI, it is recommended to delay time-sensitive NCS until a minimum of 1 month of DAPT has been given (Class I, Level B); in high-risk patients with a recent PCI, such as STEMI, a DAPT duration of at least 3 months should be considered before time-sensitive NCS (Class IIa, Level C).[7]
- ESC 2023: if patients presenting with ACS stop DAPT to undergo CABG, it is recommended they resume DAPT after surgery for at least 12 months (Class I, Level C).[1]
- ESC 2023: discontinuation of antiplatelet treatment in patients treated with an OAC is recommended after 12 months (Class I, Level B).[1]
References9ShowHide
- [1]Byrne RA, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J, 2023.PMID 37622654
- [2]Rao SV, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol, 2025.PMID 40013746
- [3]Vrints C, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J, 2024.PMID 39210710
- [4]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
- [5]Van Gelder IC, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J, 2024.PMID 39210723
- [6]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
- [7]Halvorsen S, et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J, 2022.PMID 36017553
- [8]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
- [9]De Backer J, et al. 2025 ESC Guidelines for the management of cardiovascular disease and pregnancy. Eur Heart J, 2025.PMID 40878294