In case, we refer to OAC, this can be...

In case, we refer to OAC, this can be with well-controlled adjusted-dose VKA (with TTR >70%) or with a NOAC.

General management considerations

In AF patients, stroke risk must be assessed using the CHA₂DS₂-VASc score, and bleeding risk should be assessed using the HAS-BLED score.

Stroke and bleeding risk stratification is a dynamic process, and must be performed at regular intervals.
Every effort should be made to address modifiable bleeding risk factors at every patient contact.
Established bleeding scores, e.g. HAS-BLED, should be used to draw attention to modifiable bleeding risk factors and to identify the patients for earlier review and followup.

¹⁰⁶^,¹⁰⁷^,¹¹³^,¹²²^,¹³⁰^,¹³⁶^,¹³⁷

An initial period of triple therapy should be used in most AF patients undergoing PCI, depending on presentation (ACS vs. elective), stroke vs. bleeding risk, procedural considerations (e.g. disease severity) etc.

Dual therapy with OAC plus one P2Y₁₂ inhibitor (usually clopidogrel) may be considered in patients who are predisposed to excessive bleeding risk and have low thrombotic risk.

⁵

In anticoagulated patients, pretreatment with antiplatelet therapy is appropriate if PCI planned.

Clopidogrel is the P2Y₁₂ inhibitor of choice in anticoagulated patients; prasugrel and ticagrelor should be avoided in patients also receiving aspirin due to their higher bleeding risk if used in combination as part of a TAT regimen.

⁵¹^,⁵²

In anticoagulated patients, postpone pretreatment with P2Y₁₂ inhibitors if the coronary anatomy is not known.

NOACs as part of TAT or DAT are safer than VKA (e.g. Warfarin) with respect to bleeding risk and is the preferred option in the absence of contraindications to use of these drugs.

AF patients with CHA₂DS₂-VASc score ≥2 treated with a NOAC should continue their NOAC indefinitely, with addition of antiplatelets for up to 12 months after PCI/ACS.

³⁹^,⁴⁰

DAT with rivaroxaban or dabigatran and a P2Y₁₂ inhibitor is associated with a lower risk of bleeding than TAT with warfarin.

None have been sufficiently evaluated with respect to efficacy.

³⁹^,⁴⁰

When dabigatran is used as part of DAT, the standard doses of 150 mg bid should be used to reduce the risk of ischaemic events.

As per prescribing label, dabigatran 110 mg bid can be considered in elderly patients, concomitant when PgP inhibitors (e.g. verapamil) are used, and in patients with high bleeding risk
Both dabigatran 150 mg or 110 mg bid have been shown to be non-inferior (and in the case of 150 mg bid, superior) to warfarin for stroke prevention in AF.

³⁹^,⁴⁰

When rivaroxaban is used as part of DAT, reduced dose 15 mg od should be considered.

The efficacy with respect to stroke prevention of this reduced dose in this population has not been sufficiently evaluated.

³⁹

When apixaban or edoxaban are used as part of TAT or DAT, the standard dose (5 mg bid and 60 mg od, respectively, unless label-guided dose reduction is indicated) should be selected pending results of ongoing trials.

^{Expert consensus}

When VKA is given in combination with clopidogrel and/or low-dose aspirin, the dose intensity of VKA should be carefully regulated, with a target INR range of 2.0–2.5.

Good quality anticoagulation is recommended, with a high time in therapeutic range (TTR >65–70%) aimed for.

¹⁷⁸

In patients on VKA undergoing coronary angiography and/or PCI, an uninterrupted VKA strategy is at least as safe as interrupted VKA, and seems to be much safer than interrupted VKA with bridging anticoagulation.

Patients with AF and stable vascular disease (arbitrarily defined as being free from any acute ischaemic event or repeat revascularisation for >1 year) should be managed with OAC alone.

Radial access should be considered as the default approach for coronary angiography/intervention to minimize the risk of access-related bleeding depending on operator expertise and preference.

Gastric protection with PPIs should be considered in all patients with OAC plus antiplatelet therapy

Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients.

Combination OAC plus single antiplatelet therapy (i.e., aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.

Elective or stable CAD

For NOAC-treated patients undergoing elective PCI, timed cessation (e.g. >12–48 h) before intervention may be considered, depending on the agent and renal function (see text) and use of standard local anticoagulation practices periprocedurally.

Early after PCI, such as the same evening or the next morning, NOAC therapy should be restarted.

⁵^,⁶

In patients with stable CAD and AF undergoing PCI at low bleeding risk (HAS-BLED ≤2), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) should be given for a minimum of 4 weeks (and no longer than 6 months) after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6–12 months.

⁵^,⁶

In patients with stable CAD and AF undergoing PCI at high bleeding risk (HAS-BLED ≥3), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) or DAT consisting of OAC and clopidogrel 75 mg/day should be given for 1 month after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6 months, beyond which patients would be managed on OAC alone.

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and DAT with a NOAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.

⁵^,⁶

Long-term antithrombotic therapy with OAC (beyond 12 months) is recommended in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in only very selected cases with an increased ongoing ischaemic risk.

⁵^,⁶

When the procedures require interruption of OAC for longer than 48 h in high-risk patients (i.e. TAVI or other non-PCI procedures at high bleeding risk), enoxaparin may be administered subcutaneously, although the efficacy of this strategy is uncertain.

Bridging is often considered in patients with mechanical heart valves, recent stroke/venous thromboembolism (<3 months).
Pharmacodynamic data suggest that enoxaparin might be a better option than unfractionated heparin, because of the more predictable and stable level of anticoagulation.
Such ‘bridging’ therapies may be associated with an excess bleeding risk, possibly due to dual modes of anticoagulation in the overlap periods.
When NOACs are used, timing of any bridging therapy should be tailored based on renal function and the pharmacokinetics of the specific NOAC.

^{Expert consensus}

NSTE-ACS including unstable angina and NSTEMI

In patients on OAC developing a NSTE-ACS, aspirin loading should be as in STEMI, and clopidogrel is again the P2Y₁₂ inhibitor of choice.

As clopidogrel takes considerable time to achieve its maximal antiplatelet effect in unstable patients, clopidogrel without aspirin cannot be recommended in the acute or periprocedural phase.
Pretreatment with P2Y₁₂ receptor antagonists may be withheld until the time of coronary angiography in case of an early invasive strategy within 24 h.
The use of ticagrelor or prasugrel in combination with OAC may only be considered under certain circumstances (e.g. definite stent thrombosis while on clopidogrel, aspirin, and OAC).

⁵^,⁶

Administer unfractionated heparin or bivalirudin only as bailout (but avoiding GPIIb/IIIa inhibitors) or if INR≤2 in a patient on VKA, balancing the acute need for additional antithrombotic therapy with the excess bleeding risk and the ‘thrombus burden’.

Glycoprotein IIb/IIIa inhibitors should be avoided unless for bail-out situations due to the increased risk of bleeding associated with their use.

^{Expert consensus}

TAT is still the recommended initial treatment for the first month after PCI or an ACS in AF patients with a high ischemic risk and a low bleeding risk.

¹^,⁵^,⁶

An early invasive strategy (within 24 h) should be preferred among AF patients with moderate to high-risk NSTE-ACS in order to expedite treatment allocation (medical vs. PCI vs. coronary artery bypass grafting) and to determine the optimal antithrombotic regimen.

¹^,⁵

In AF patients with ACS at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 3–6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75mg/day (or alternatively, aspirin 75–100 mg/day).

¹^,⁵^,⁶

In patients with ACS and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day).

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed with OAC alone.

⁵^,⁶

Long-term antithrombotic therapy (beyond 12 months) with OAC, whether with VKA or NOAC, is recommended in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in very selected cases, e.g. extensive multivessel CAD, last remaining patent coronary artery, stenting of the left main stem or a proximal bifurcation, recurrent MIs etc.

⁵^,⁶

Primary PCI

When anticoagulated patients present with a STEMI, they should be triaged for primary PCI regardless of the anticipated time to PCI-mediated reperfusion.

¹^,^4–6

In the setting of STEMI, radial access for primary PCI is the best option, when feasible, to avoid procedural bleeding depending on operator expertise and preference.

¹^,^4–6

In patients with STEMI and AF at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day).

¹^,⁵^,⁶

In patients with STEMI and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day).

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.

¹^,⁵^,⁶

Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.

⁵^,⁶

General management considerations
In AF patients, stroke risk must be assessed using the CHA₂DS₂-VASc score, and bleeding risk should be assessed using the HAS-BLED score. Stroke and bleeding risk stratification is a dynamic process, and must be performed at regular intervals. Every effort should be made to address modifiable bleeding risk factors at every patient contact. Established bleeding scores, e.g. HAS-BLED, should be used to draw attention to modifiable bleeding risk factors and to identify the patients for earlier review and followup.		¹⁰⁶^,¹⁰⁷^,¹¹³^,¹²²^,¹³⁰^,¹³⁶^,¹³⁷
An initial period of triple therapy should be used in most AF patients undergoing PCI, depending on presentation (ACS vs. elective), stroke vs. bleeding risk, procedural considerations (e.g. disease severity) etc. Dual therapy with OAC plus one P2Y₁₂ inhibitor (usually clopidogrel) may be considered in patients who are predisposed to excessive bleeding risk and have low thrombotic risk.		⁵
In anticoagulated patients, pretreatment with antiplatelet therapy is appropriate if PCI planned. Clopidogrel is the P2Y₁₂ inhibitor of choice in anticoagulated patients; prasugrel and ticagrelor should be avoided in patients also receiving aspirin due to their higher bleeding risk if used in combination as part of a TAT regimen.		⁵¹^,⁵²
In anticoagulated patients, postpone pretreatment with P2Y₁₂ inhibitors if the coronary anatomy is not known.
NOACs as part of TAT or DAT are safer than VKA (e.g. Warfarin) with respect to bleeding risk and is the preferred option in the absence of contraindications to use of these drugs. AF patients with CHA₂DS₂-VASc score ≥2 treated with a NOAC should continue their NOAC indefinitely, with addition of antiplatelets for up to 12 months after PCI/ACS.		³⁹^,⁴⁰
DAT with rivaroxaban or dabigatran and a P2Y₁₂ inhibitor is associated with a lower risk of bleeding than TAT with warfarin. None have been sufficiently evaluated with respect to efficacy.		³⁹^,⁴⁰
When dabigatran is used as part of DAT, the standard doses of 150 mg bid should be used to reduce the risk of ischaemic events. As per prescribing label, dabigatran 110 mg bid can be considered in elderly patients, concomitant when PgP inhibitors (e.g. verapamil) are used, and in patients with high bleeding risk Both dabigatran 150 mg or 110 mg bid have been shown to be non-inferior (and in the case of 150 mg bid, superior) to warfarin for stroke prevention in AF.		³⁹^,⁴⁰
When rivaroxaban is used as part of DAT, reduced dose 15 mg od should be considered. The efficacy with respect to stroke prevention of this reduced dose in this population has not been sufficiently evaluated.		³⁹
When apixaban or edoxaban are used as part of TAT or DAT, the standard dose (5 mg bid and 60 mg od, respectively, unless label-guided dose reduction is indicated) should be selected pending results of ongoing trials.		^{Expert consensus}
When VKA is given in combination with clopidogrel and/or low-dose aspirin, the dose intensity of VKA should be carefully regulated, with a target INR range of 2.0–2.5. Good quality anticoagulation is recommended, with a high time in therapeutic range (TTR >65–70%) aimed for.		¹⁷⁸
In patients on VKA undergoing coronary angiography and/or PCI, an uninterrupted VKA strategy is at least as safe as interrupted VKA, and seems to be much safer than interrupted VKA with bridging anticoagulation.		¹
Patients with AF and stable vascular disease (arbitrarily defined as being free from any acute ischaemic event or repeat revascularisation for >1 year) should be managed with OAC alone.		¹
Radial access should be considered as the default approach for coronary angiography/intervention to minimize the risk of access-related bleeding depending on operator expertise and preference.		¹
Gastric protection with PPIs should be considered in all patients with OAC plus antiplatelet therapy		¹
Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients. Combination OAC plus single antiplatelet therapy (i.e., aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.		¹
Elective or stable CAD
For NOAC-treated patients undergoing elective PCI, timed cessation (e.g. >12–48 h) before intervention may be considered, depending on the agent and renal function (see text) and use of standard local anticoagulation practices periprocedurally. Early after PCI, such as the same evening or the next morning, NOAC therapy should be restarted.		⁵^,⁶
In patients with stable CAD and AF undergoing PCI at low bleeding risk (HAS-BLED ≤2), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) should be given for a minimum of 4 weeks (and no longer than 6 months) after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6–12 months.		⁵^,⁶
In patients with stable CAD and AF undergoing PCI at high bleeding risk (HAS-BLED ≥3), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) or DAT consisting of OAC and clopidogrel 75 mg/day should be given for 1 month after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6 months, beyond which patients would be managed on OAC alone. In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and DAT with a NOAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.		⁵^,⁶
Long-term antithrombotic therapy with OAC (beyond 12 months) is recommended in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in only very selected cases with an increased ongoing ischaemic risk.		⁵^,⁶
When the procedures require interruption of OAC for longer than 48 h in high-risk patients (i.e. TAVI or other non-PCI procedures at high bleeding risk), enoxaparin may be administered subcutaneously, although the efficacy of this strategy is uncertain. Bridging is often considered in patients with mechanical heart valves, recent stroke/venous thromboembolism (<3 months). Pharmacodynamic data suggest that enoxaparin might be a better option than unfractionated heparin, because of the more predictable and stable level of anticoagulation. Such ‘bridging’ therapies may be associated with an excess bleeding risk, possibly due to dual modes of anticoagulation in the overlap periods. When NOACs are used, timing of any bridging therapy should be tailored based on renal function and the pharmacokinetics of the specific NOAC.		^{Expert consensus}
NSTE-ACS including unstable angina and NSTEMI
In patients on OAC developing a NSTE-ACS, aspirin loading should be as in STEMI, and clopidogrel is again the P2Y₁₂ inhibitor of choice. As clopidogrel takes considerable time to achieve its maximal antiplatelet effect in unstable patients, clopidogrel without aspirin cannot be recommended in the acute or periprocedural phase. Pretreatment with P2Y₁₂ receptor antagonists may be withheld until the time of coronary angiography in case of an early invasive strategy within 24 h. The use of ticagrelor or prasugrel in combination with OAC may only be considered under certain circumstances (e.g. definite stent thrombosis while on clopidogrel, aspirin, and OAC).		⁵^,⁶
Administer unfractionated heparin or bivalirudin only as bailout (but avoiding GPIIb/IIIa inhibitors) or if INR≤2 in a patient on VKA, balancing the acute need for additional antithrombotic therapy with the excess bleeding risk and the ‘thrombus burden’. Glycoprotein IIb/IIIa inhibitors should be avoided unless for bail-out situations due to the increased risk of bleeding associated with their use.		^{Expert consensus}
TAT is still the recommended initial treatment for the first month after PCI or an ACS in AF patients with a high ischemic risk and a low bleeding risk.		¹^,⁵^,⁶
An early invasive strategy (within 24 h) should be preferred among AF patients with moderate to high-risk NSTE-ACS in order to expedite treatment allocation (medical vs. PCI vs. coronary artery bypass grafting) and to determine the optimal antithrombotic regimen.		¹^,⁵
In AF patients with ACS at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 3–6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75mg/day (or alternatively, aspirin 75–100 mg/day).		¹^,⁵^,⁶
In patients with ACS and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day). In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed with OAC alone.		⁵^,⁶
Long-term antithrombotic therapy (beyond 12 months) with OAC, whether with VKA or NOAC, is recommended in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in very selected cases, e.g. extensive multivessel CAD, last remaining patent coronary artery, stenting of the left main stem or a proximal bifurcation, recurrent MIs etc.		⁵^,⁶
Primary PCI
When anticoagulated patients present with a STEMI, they should be triaged for primary PCI regardless of the anticipated time to PCI-mediated reperfusion.		¹^,^4–6
In the setting of STEMI, radial access for primary PCI is the best option, when feasible, to avoid procedural bleeding depending on operator expertise and preference.		¹^,^4–6
In patients with STEMI and AF at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day).		¹^,⁵^,⁶
In patients with STEMI and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day). In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.		¹^,⁵^,⁶
Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.		⁵^,⁶

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General management considerations

In AF patients, stroke risk must be assessed using the CHA₂DS₂-VASc score, and bleeding risk should be assessed using the HAS-BLED score.

Stroke and bleeding risk stratification is a dynamic process, and must be performed at regular intervals.
Every effort should be made to address modifiable bleeding risk factors at every patient contact.
Established bleeding scores, e.g. HAS-BLED, should be used to draw attention to modifiable bleeding risk factors and to identify the patients for earlier review and followup.

¹⁰⁶^,¹⁰⁷^,¹¹³^,¹²²^,¹³⁰^,¹³⁶^,¹³⁷

Dual therapy with OAC plus one P2Y₁₂ inhibitor (usually clopidogrel) may be considered in patients who are predisposed to excessive bleeding risk and have low thrombotic risk.

⁵

In anticoagulated patients, pretreatment with antiplatelet therapy is appropriate if PCI planned.

Clopidogrel is the P2Y₁₂ inhibitor of choice in anticoagulated patients; prasugrel and ticagrelor should be avoided in patients also receiving aspirin due to their higher bleeding risk if used in combination as part of a TAT regimen.

⁵¹^,⁵²

In anticoagulated patients, postpone pretreatment with P2Y₁₂ inhibitors if the coronary anatomy is not known.

NOACs as part of TAT or DAT are safer than VKA (e.g. Warfarin) with respect to bleeding risk and is the preferred option in the absence of contraindications to use of these drugs.

AF patients with CHA₂DS₂-VASc score ≥2 treated with a NOAC should continue their NOAC indefinitely, with addition of antiplatelets for up to 12 months after PCI/ACS.

³⁹^,⁴⁰

DAT with rivaroxaban or dabigatran and a P2Y₁₂ inhibitor is associated with a lower risk of bleeding than TAT with warfarin.

None have been sufficiently evaluated with respect to efficacy.

³⁹^,⁴⁰

When dabigatran is used as part of DAT, the standard doses of 150 mg bid should be used to reduce the risk of ischaemic events.

As per prescribing label, dabigatran 110 mg bid can be considered in elderly patients, concomitant when PgP inhibitors (e.g. verapamil) are used, and in patients with high bleeding risk
Both dabigatran 150 mg or 110 mg bid have been shown to be non-inferior (and in the case of 150 mg bid, superior) to warfarin for stroke prevention in AF.

³⁹^,⁴⁰

When rivaroxaban is used as part of DAT, reduced dose 15 mg od should be considered.

The efficacy with respect to stroke prevention of this reduced dose in this population has not been sufficiently evaluated.

³⁹

^{Expert consensus}

When VKA is given in combination with clopidogrel and/or low-dose aspirin, the dose intensity of VKA should be carefully regulated, with a target INR range of 2.0–2.5.

Good quality anticoagulation is recommended, with a high time in therapeutic range (TTR >65–70%) aimed for.

¹⁷⁸

Patients with AF and stable vascular disease (arbitrarily defined as being free from any acute ischaemic event or repeat revascularisation for >1 year) should be managed with OAC alone.

Radial access should be considered as the default approach for coronary angiography/intervention to minimize the risk of access-related bleeding depending on operator expertise and preference.

Gastric protection with PPIs should be considered in all patients with OAC plus antiplatelet therapy

Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients.

Combination OAC plus single antiplatelet therapy (i.e., aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.

Elective or stable CAD

Early after PCI, such as the same evening or the next morning, NOAC therapy should be restarted.

⁵^,⁶

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and DAT with a NOAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.

⁵^,⁶

Long-term antithrombotic therapy with OAC (beyond 12 months) is recommended in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in only very selected cases with an increased ongoing ischaemic risk.

⁵^,⁶

Bridging is often considered in patients with mechanical heart valves, recent stroke/venous thromboembolism (<3 months).
Pharmacodynamic data suggest that enoxaparin might be a better option than unfractionated heparin, because of the more predictable and stable level of anticoagulation.
Such ‘bridging’ therapies may be associated with an excess bleeding risk, possibly due to dual modes of anticoagulation in the overlap periods.
When NOACs are used, timing of any bridging therapy should be tailored based on renal function and the pharmacokinetics of the specific NOAC.

^{Expert consensus}

NSTE-ACS including unstable angina and NSTEMI

In patients on OAC developing a NSTE-ACS, aspirin loading should be as in STEMI, and clopidogrel is again the P2Y₁₂ inhibitor of choice.

As clopidogrel takes considerable time to achieve its maximal antiplatelet effect in unstable patients, clopidogrel without aspirin cannot be recommended in the acute or periprocedural phase.
Pretreatment with P2Y₁₂ receptor antagonists may be withheld until the time of coronary angiography in case of an early invasive strategy within 24 h.
The use of ticagrelor or prasugrel in combination with OAC may only be considered under certain circumstances (e.g. definite stent thrombosis while on clopidogrel, aspirin, and OAC).

⁵^,⁶

Glycoprotein IIb/IIIa inhibitors should be avoided unless for bail-out situations due to the increased risk of bleeding associated with their use.

^{Expert consensus}

TAT is still the recommended initial treatment for the first month after PCI or an ACS in AF patients with a high ischemic risk and a low bleeding risk.

¹^,⁵^,⁶

¹^,⁵

¹^,⁵^,⁶

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed with OAC alone.

⁵^,⁶

Long-term antithrombotic therapy (beyond 12 months) with OAC, whether with VKA or NOAC, is recommended in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in very selected cases, e.g. extensive multivessel CAD, last remaining patent coronary artery, stenting of the left main stem or a proximal bifurcation, recurrent MIs etc.

⁵^,⁶

Primary PCI

When anticoagulated patients present with a STEMI, they should be triaged for primary PCI regardless of the anticipated time to PCI-mediated reperfusion.

¹^,^4–6

In the setting of STEMI, radial access for primary PCI is the best option, when feasible, to avoid procedural bleeding depending on operator expertise and preference.

¹^,^4–6

¹^,⁵^,⁶

In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.

¹^,⁵^,⁶

Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients.

Combination OAC plus single antiplatelet therapy (i.e. aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.

⁵^,⁶

General management considerations
In AF patients, stroke risk must be assessed using the CHA₂DS₂-VASc score, and bleeding risk should be assessed using the HAS-BLED score. Stroke and bleeding risk stratification is a dynamic process, and must be performed at regular intervals. Every effort should be made to address modifiable bleeding risk factors at every patient contact. Established bleeding scores, e.g. HAS-BLED, should be used to draw attention to modifiable bleeding risk factors and to identify the patients for earlier review and followup.		¹⁰⁶^,¹⁰⁷^,¹¹³^,¹²²^,¹³⁰^,¹³⁶^,¹³⁷
An initial period of triple therapy should be used in most AF patients undergoing PCI, depending on presentation (ACS vs. elective), stroke vs. bleeding risk, procedural considerations (e.g. disease severity) etc. Dual therapy with OAC plus one P2Y₁₂ inhibitor (usually clopidogrel) may be considered in patients who are predisposed to excessive bleeding risk and have low thrombotic risk.		⁵
In anticoagulated patients, pretreatment with antiplatelet therapy is appropriate if PCI planned. Clopidogrel is the P2Y₁₂ inhibitor of choice in anticoagulated patients; prasugrel and ticagrelor should be avoided in patients also receiving aspirin due to their higher bleeding risk if used in combination as part of a TAT regimen.		⁵¹^,⁵²
In anticoagulated patients, postpone pretreatment with P2Y₁₂ inhibitors if the coronary anatomy is not known.
NOACs as part of TAT or DAT are safer than VKA (e.g. Warfarin) with respect to bleeding risk and is the preferred option in the absence of contraindications to use of these drugs. AF patients with CHA₂DS₂-VASc score ≥2 treated with a NOAC should continue their NOAC indefinitely, with addition of antiplatelets for up to 12 months after PCI/ACS.		³⁹^,⁴⁰
DAT with rivaroxaban or dabigatran and a P2Y₁₂ inhibitor is associated with a lower risk of bleeding than TAT with warfarin. None have been sufficiently evaluated with respect to efficacy.		³⁹^,⁴⁰
When dabigatran is used as part of DAT, the standard doses of 150 mg bid should be used to reduce the risk of ischaemic events. As per prescribing label, dabigatran 110 mg bid can be considered in elderly patients, concomitant when PgP inhibitors (e.g. verapamil) are used, and in patients with high bleeding risk Both dabigatran 150 mg or 110 mg bid have been shown to be non-inferior (and in the case of 150 mg bid, superior) to warfarin for stroke prevention in AF.		³⁹^,⁴⁰
When rivaroxaban is used as part of DAT, reduced dose 15 mg od should be considered. The efficacy with respect to stroke prevention of this reduced dose in this population has not been sufficiently evaluated.		³⁹
When apixaban or edoxaban are used as part of TAT or DAT, the standard dose (5 mg bid and 60 mg od, respectively, unless label-guided dose reduction is indicated) should be selected pending results of ongoing trials.		^{Expert consensus}
When VKA is given in combination with clopidogrel and/or low-dose aspirin, the dose intensity of VKA should be carefully regulated, with a target INR range of 2.0–2.5. Good quality anticoagulation is recommended, with a high time in therapeutic range (TTR >65–70%) aimed for.		¹⁷⁸
In patients on VKA undergoing coronary angiography and/or PCI, an uninterrupted VKA strategy is at least as safe as interrupted VKA, and seems to be much safer than interrupted VKA with bridging anticoagulation.		¹
Patients with AF and stable vascular disease (arbitrarily defined as being free from any acute ischaemic event or repeat revascularisation for >1 year) should be managed with OAC alone.		¹
Radial access should be considered as the default approach for coronary angiography/intervention to minimize the risk of access-related bleeding depending on operator expertise and preference.		¹
Gastric protection with PPIs should be considered in all patients with OAC plus antiplatelet therapy		¹
Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients. Combination OAC plus single antiplatelet therapy (i.e., aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.		¹
Elective or stable CAD
For NOAC-treated patients undergoing elective PCI, timed cessation (e.g. >12–48 h) before intervention may be considered, depending on the agent and renal function (see text) and use of standard local anticoagulation practices periprocedurally. Early after PCI, such as the same evening or the next morning, NOAC therapy should be restarted.		⁵^,⁶
In patients with stable CAD and AF undergoing PCI at low bleeding risk (HAS-BLED ≤2), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) should be given for a minimum of 4 weeks (and no longer than 6 months) after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6–12 months.		⁵^,⁶
In patients with stable CAD and AF undergoing PCI at high bleeding risk (HAS-BLED ≥3), TAT (OAC, aspirin 75–100 mg daily, clopidogrel 75 mg daily) or DAT consisting of OAC and clopidogrel 75 mg/day should be given for 1 month after PCI following which DAT with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) should be continued for up to 6 months, beyond which patients would be managed on OAC alone. In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and DAT with a NOAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.		⁵^,⁶
Long-term antithrombotic therapy with OAC (beyond 12 months) is recommended in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in only very selected cases with an increased ongoing ischaemic risk.		⁵^,⁶
When the procedures require interruption of OAC for longer than 48 h in high-risk patients (i.e. TAVI or other non-PCI procedures at high bleeding risk), enoxaparin may be administered subcutaneously, although the efficacy of this strategy is uncertain. Bridging is often considered in patients with mechanical heart valves, recent stroke/venous thromboembolism (<3 months). Pharmacodynamic data suggest that enoxaparin might be a better option than unfractionated heparin, because of the more predictable and stable level of anticoagulation. Such ‘bridging’ therapies may be associated with an excess bleeding risk, possibly due to dual modes of anticoagulation in the overlap periods. When NOACs are used, timing of any bridging therapy should be tailored based on renal function and the pharmacokinetics of the specific NOAC.		^{Expert consensus}
NSTE-ACS including unstable angina and NSTEMI
In patients on OAC developing a NSTE-ACS, aspirin loading should be as in STEMI, and clopidogrel is again the P2Y₁₂ inhibitor of choice. As clopidogrel takes considerable time to achieve its maximal antiplatelet effect in unstable patients, clopidogrel without aspirin cannot be recommended in the acute or periprocedural phase. Pretreatment with P2Y₁₂ receptor antagonists may be withheld until the time of coronary angiography in case of an early invasive strategy within 24 h. The use of ticagrelor or prasugrel in combination with OAC may only be considered under certain circumstances (e.g. definite stent thrombosis while on clopidogrel, aspirin, and OAC).		⁵^,⁶
Administer unfractionated heparin or bivalirudin only as bailout (but avoiding GPIIb/IIIa inhibitors) or if INR≤2 in a patient on VKA, balancing the acute need for additional antithrombotic therapy with the excess bleeding risk and the ‘thrombus burden’. Glycoprotein IIb/IIIa inhibitors should be avoided unless for bail-out situations due to the increased risk of bleeding associated with their use.		^{Expert consensus}
TAT is still the recommended initial treatment for the first month after PCI or an ACS in AF patients with a high ischemic risk and a low bleeding risk.		¹^,⁵^,⁶
An early invasive strategy (within 24 h) should be preferred among AF patients with moderate to high-risk NSTE-ACS in order to expedite treatment allocation (medical vs. PCI vs. coronary artery bypass grafting) and to determine the optimal antithrombotic regimen.		¹^,⁵
In AF patients with ACS at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 3–6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75mg/day (or alternatively, aspirin 75–100 mg/day).		¹^,⁵^,⁶
In patients with ACS and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day). In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed with OAC alone.		⁵^,⁶
Long-term antithrombotic therapy (beyond 12 months) with OAC, whether with VKA or NOAC, is recommended in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may be considered in very selected cases, e.g. extensive multivessel CAD, last remaining patent coronary artery, stenting of the left main stem or a proximal bifurcation, recurrent MIs etc.		⁵^,⁶
Primary PCI
When anticoagulated patients present with a STEMI, they should be triaged for primary PCI regardless of the anticipated time to PCI-mediated reperfusion.		¹^,^4–6
In the setting of STEMI, radial access for primary PCI is the best option, when feasible, to avoid procedural bleeding depending on operator expertise and preference.		¹^,^4–6
In patients with STEMI and AF at low risk of bleeding (HAS-BLED 0–2), the initial use of TAT (OAC, aspirin and clopidogrel) should be considered for 6 months following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day).		¹^,⁵^,⁶
In patients with STEMI and AF at high risk of bleeding (HAS-BLED ≥3), the initial use of TAT (OAC, aspirin, and clopidogrel) should be considered for 4 weeks following PCI irrespective of stent type; this should be followed by long term DAT (up to 12 months) with OAC and clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day). In patients at very high bleeding risk (e.g. recent bleeding event), aspirin may be omitted, and dual therapy with OAC and clopidogrel 75 mg/day continued for 3–6 months, beyond which patients would be managed on OAC alone.		¹^,⁵^,⁶
Long-term antithrombotic therapy (beyond 12 months) is recommended with OAC in all patients. Combination OAC plus single antiplatelet therapy (i.e. aspirin) may sometimes be continued in very selected cases, e.g. stenting of the left main, proximal bifurcation, recurrent MIs etc.		⁵^,⁶

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