Antithrombotic Management of Atrial Fibrillation Patients Presenting with Coronary Artery Disease: A Consensus Document of the Chinese Society of Cardiology : Cardiology Discovery

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Consensus and Guideline

Antithrombotic Management of Atrial Fibrillation Patients Presenting with Coronary Artery Disease: A Consensus Document of the Chinese Society of Cardiology

Editor(s): Fu, Xiaoxia; Xu., Tianyu

Author Information
Cardiology Discovery 1(1):p 15-28, March 2021. | DOI: 10.1097/CD9.0000000000000020
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Abstract

Introduction

Coronary artery disease (CAD) and atrial fibrillation (AF) coexist commonly in patients with cardiovascular risk factors. The incidence of AF in patients with CAD is 6%–21%,[1] and 20%–30% of patients with AF also have CAD.[2–4] Patients with CAD require antiplatelet therapy to reduce ischemic events; meanwhile, patients with AF at high risk of thromboembolism require oral anticoagulant (OAC) therapy to reduce thromboembolic events such as stroke.[5] In patients with both CAD and AF, the combined use of an antiplatelet agent and OAC can effectively prevent ischemic and thromboembolic events, while increasing the risk of bleeding.[6] The optimal antithrombotic regimen in patients with both CAD and AF has been a hot topic in clinical practice. In recent years, expert consensuses on antithrombotic therapy in patients with acute coronary syndrome (ACS) and/or those with AF undergoing percutaneous coronary intervention (PCI) have been published in Europe[7–9] and North America,[6,10,11] and have been updated to their third edition.

Based on published clinical evidence, this consensus incorporates relevant international and Chinese guidelines, consensuses, and expert recommendations, and addresses the issues encountered in the clinical practice of antithrombotic therapy in patients with AF and CAD. This consensus, endorsed by the Chinese Society of Cardiology, provides a systematic review of relevant studies and assesses their strength of evidence (SOE). In the areas where evidence is lacking, recommendations are provided based on the discussion from the expert group responsible for developing this consensus. For clinicians to understand the current SOEs and recommendations, the consensus uses “+ +,” “+/±,” and “–” to represent different recommendation classes [Table 1].

Table 1 - Instructions for recommendation classification in this consensus
Type of evidence Recommendation class Symbol
The research evidence shows that the treatment or procedure provides obvious benefits and is supported by at least one widely recognized RCT or strong observational evidence and consensus opinions of experts. The treatment or procedure should be recommended ++
The research evidence and/or consensus opinions of experts indicate that the treatment or procedure is effective and is supported by RCTs that are not widely recognized. The treatment or procedure may be reasonable +/±
The research evidence or consensus opinions of experts do not recommend the treatment or procedure. The treatment or procedure should not be recommended
The classification method for recommendations used in this consensus is not equivalent to the class of recommendation (Classes I, II, and III) and level of evidence (Levels A, B, and C) in the guidelines.RCT: Randomized controlled trial.

Assessment of ischemic and bleeding risk

Patients benefit from the assessment of thromboembolism/ischemia and bleeding risk prior to the initiation of antithrombotic therapy.

Risk of thromboembolism/stroke

Thromboembolic event is the leading cause of death and disability among patients with AF, and stroke is the most common manifestation of embolism in AF.[12] The risk of thromboembolism in patients with AF is continuous and constantly changing, which should be regularly evaluated.[13] Assessment of thromboembolic risk using the CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, aged 65 to 74 years, and sex category) [Table 2] is currently recommended in all patients with non-valvular atrial fibrillation (NVAF).[14] The CHA2DS2-VASc score was used in 4 recently published randomized controlled trials (RCTs) in patients with both CAD and AF.[15–18]

Table 2 - CHA2DS2-VASc score for the risk of thromboembolism/stroke in patients with NVAF[14]
Risk factor Score (point)
Chronic heart failure/left ventricular dysfunction (C) 1
Hypertension (H) 1
Age ≥75 years (A) 2
Diabetes mellitus (D) 1
Stroke/TIA/Thromboembolism (S) 2
Vascular disease (V) 1
Aged 65–74 years (A) 1
Sex (female) (Sc) 1
Maximum score 9
Vascular disease refers to myocardial infarction, complex aortic plaque, and peripheral arterial disease.NVAF: Non-valvular atrial fibrillation; TIA: Transient ischemic attack.

Recommendations of anticoagulation therapy among patients with both CAD and NVAF[12,13,19,20]: (1) For patients with a CHA2DS2-VASc score ≥2 (male)/3 (female), long-term OAC therapy should be performed; (2) for compliant patients and a CHA2DS2-VASc score of 1 (male)/2 (female), anticoagulation therapy is also recommended; and (3) for patients with a CHA2DS2-VASc score of 0 (male)/1 (female), anticoagulation therapy should be avoided for preventing thromboembolism. It is acknowledged that the risks of thrombosis for patients with paroxysmal and permanent/persistent AF are almost the same; anticoagulation therapy should be subscribed according to the patient's risk stratification, rather than the type of AF. Atrial flutter and AF should be treated with the same anticoagulation strategy.[21] Assessment of thromboembolic risk is unnecessary in patients with valvular AF because valvular AF is always indicated for long-term anticoagulation therapy.

Risk of ischemia/thrombosis

The occurrence of ischemic events in the previous years is the strongest predictor of repeat ischemic events [Table 3].[22] The risk of ischemic events is much higher in patients with a history of ACS than patients with stable CAD or patients undergoing coronary stenting.[23] Advanced age, diabetes mellitus, chronic kidney disease (Creatinine clearance rate (Ccr) 15–59 mL/min), diffuse CAD, low left ventricular ejection fraction, and inappropriate stent size are important risk factors for ischemic events.[6]

Table 3 - Factors that increase the risk of ischemia (including stent thrombosis) or bleeding[6]
Factors that increase the risk of ischemia/stent thrombosis
Increased risk of ischemia Increased risk of stent thrombosis Increased risk of bleeding
Advanced agePresentation of ACSPrevious history of multiple myocardial infarctionsDiffuse CADDiabetes mellitusChronic kidney disease (Ccr 15–59 mL/min) Presentation of ACSDiabetes mellitusLeft ventricular ejection fraction <40%First-generation drug-eluting stentsSmall stent sizeInadequate stent expansionSmall diameter of the stented vesselStent oversized in lengthBifurcated stentStent restenosis Previous history of bleedingCombined use of multiple antithrombotic drugsAdvanced ageLow body weightChronic kidney disease (on hemodialysis or Ccr < 15 mL/min)Diabetes mellitusAnemiaLong-term use of steroids or non-steroidal anti-inflammatory drugsPrevious history of cerebral hemorrhage, ischemic stroke, or other intracranial diseases
ACS: Acute coronary syndrome; CAD: Coronary artery disease; Ccr: Creatinine clearance rate.

The risk of ischemic events in patients with AF undergoing PCI can be assessed using the SYNTAX,[24] SYNTAX II[25] [Table 4], or the Global Registry of Acute Coronary Events (GRACE) score.[26] Both SYNTAX and GRACE scores can predict the risk of ischemic events and mortality in patients with AF undergoing coronary stent implantation.[27] The risk of mid- and long-term ischemic events in patients undergoing elective PCI can be evaluated using the SYNTAX and SYNTAX II scores.[28,29] The risk of in-hospital and out-hospital mortality in patients with ACS can be evaluated using the GRACE score.[30] The GRACE score is superior to the thrombolysis in myocardial infarction (TIMI) score in predicting in-hospital mortality among Chinese patients with non-ST segment elevation myocardial infarction (NSTEMI).[31]

Table 4 - SYNTAX and SYNTAX II scores in patients undergoing elective PCI[24,25]
Number of variables (items) for assessing risk factors

Risk score Clinical factor CAG factor Specific variable Risk stratification
SYNTAX 0 11 CAG factors: Coronary artery distribution type, stenosis site, presence of complete occlusion, triple bifurcation lesions, dual bifurcation lesions, aortic ostial lesions, severe distortion, lesion length > 20 mm, severe calcification, thrombosis, diffuse disease/small vessel disease. Low risk: 0–22 pointsMedium risk: 23–32 pointsHigh risk: ≥33 points
SYNTAX II 6 12 CAG factors: Unprotected left main disease is also included in addition to the 11 factors of SYNTAX score.Clinical factors: age, sex, Ccr left ventricular ejection fraction, peripheral vascular disease, and chronic obstructive pulmonary disease. Low risk: 0–21 pointsMedium risk: 22–28 pointsHigh risk: ≥29 points
CAG: Coronary angiography; Ccr: Creatinine clearance rate; PCI: Percutaneous coronary intervention.

Risk of bleeding

The risk of bleeding is associated with the use of antithrombotic drugs and the intensity of antithrombotic therapy. For patients receiving single antiplatelet therapy, the overall risk of bleeding of aspirin and clopidogrel is comparable, while clopidogrel is associated with lower rates of bleeding due to gastrointestinal (GI) bleeding.[32] The bleeding risk of prasugrel and ticagrelor is higher than that of clopidogrel.[33,34] The risk of major and fatal bleeding with non-vitamin K antagonist oral anticoagulants (NOACs) is lower than that of warfarin.[19] A history of bleeding, advanced age, low body weight, chronic kidney disease (on hemodialysis or Ccr < 15 mL/min), diabetes mellitus, anemia, and long-term use of steroids or non-steroidal anti-inflammatory drugs (NSAIDs) are all associated with a high risk of bleeding [Table 3].

HAS-BLED score [Table 5] is recommended for assessing bleeding risk in patients with CAD and AF.[35] Bleeding risk assessment is mainly used to screen the risk factors for reversible bleeding, such as inadequate control of hypertension (systolic blood pressure >160 mmHg), labile international normalized ratio (INR), concurrent use of drugs that may increase the risk of bleeding (eg, NSAIDs, etc), and alcoholism.[6] HAS-BLED score ≥3 indicates an increased risk of bleeding. However, the increased risk of bleeding should not be regarded as a contraindication of antithrombotic therapy. Adequate attention should be paid to the screening and correction of reversible bleeding risk factors. Close follow-up and monitoring should be implemented following the initiation of antithrombotic therapy.[13,19]

Table 5 - HAS-BLED score[35]
Risk factor Score (point)
Hypertension (H) 1
Abnormal renal or liver function (1 point each) (A) 1 or 2
Stroke (S) 1
Bleeding§ (B) 1
Labile INR|| (L) 1
Elderly (aged >65 years) (E) 1
Drug or alcohol (one point each) (D) 1 or 2
Total score 9
Hypertension is defined as systolic blood pressure >160 mmHg.
Abnormal renal function is defined as chronic dialysis or kidney transplantation or serum creatinine ≥200 μmol/L.
Abnormal liver function is defined as chronic liver disease (eg, liver fibrosis) or bilirubin >2 times the normal upper limit and alanine aminotransferase >3 times the normal upper limit.
§Bleeding refers to the history of bleeding and/or bleeding tendency.
||Easily fluctuating INR refers to unstable INRs with a time in therapeutic range <60%.
Drug refers to the concurrent use of antiplatelet drugs or non-steroidal anti-inflammatory drugs.INR: International normalized ratio.

Antithrombotic therapy

Antithrombotic therapy in patients with AF presenting with ACS and/or undergoing PCI

Present evidence

Several RCTs have been published to evaluate the efficacy and safety of different antithrombotic regimens in patients with AF and ACS and/or undergoing PCI [Table 6].[15–18,36,37]

Table 6 - Published major RCTs of different antithrombotic regimens in patients with AF and ACS and/or undergoing PCI
Name of study Type of study Study population Study group assignment Key result
WOEST[36] RCT, open-label 573 patients receiving OAC and undergoing PCI (69% with AF) VKA + clopidogrel group and VKA + DAPT group Dual antithrombotic therapy with VKA + clopidogrel is associated with a reduced risk of bleeding versus triple antithrombotic therapy.
ISAR-TRIPLE[37] RCT, open-label 614 patients receiving OAC and already having undergone DES implantation 6-week VKA + DAPT group and 6-month VKA + DAPT group No statistically significant difference in net clinical benefit (the composite endpoint of ischemia and bleeding) was observed between 6-week and 6-month triple antithrombotic therapy.
PIONEER AF-PCI[15] RCT, open-label 2124 Patients with NVAF and ACS and/or undergoing PCI Rivaroxaban 15 mg once daily + P2Y12 receptor antagonist group, rivaroxaban 2.5 mg twice daily + DAPT group, and VKA + DAPT group Both rivaroxaban regimens consistently reduced clinically significant bleeding compared with warfarin.
RE-DUAL PCI[16] RCT, open-label 2725 Patients with NVAF and ACS and/or undergoing PCI Dabigatran 110 mg twice daily + P2Y12 receptor antagonist group, dabigatran 150 mg twice daily + P2Y12 receptor antagonist group, and warfarin + DAPT group Both dabigatran regimens consistently reduced major or clinically relevant non-major bleeding compared with triple therapy with warfarin.
AUGUSTUS[17] RCT, open-label, 2 × 2 factorial design 4614 Patients with NVAF and ACS and/or undergoing PCI Based on the P2Y12 receptor antagonist, the patients were randomized twice: apixaban 5 mg twice daily or VKA group and aspirin or placebo group The antithrombotic regimen containing apixaban had more significant efficacy for the reduction of the risk of major bleeding and clinically relevant non-major bleeding versus the antithrombotic regimen containing a VKA; the dual antithrombotic therapy was associated with significantly reduced risk of bleeding versus triple antithrombotic therapy.
ENTRUST-AF-PCI[18] RCT, open-label 1506 Patients with NVAF and ACS and/or undergoing PCI Edoxaban 60 mg once daily + P2Y12 receptor antagonist group and VKA + DAPT group The edoxaban-based dual antithrombotic therapy was non-inferior for bleeding compared with the VKA-based triple antithrombotic therapy, but had insignificant efficacy for the reduction of the risk of bleeding.
ACS: Acute coronary syndrome; AF: Atrial fibrillation; DAPT: Dual antiplatelet therapy; DES: Drug-eluting stent; NVAF: Non-valvular atrial fibrillation; OAC: Oral anticoagulant; PCI: Percutaneous coronary intervention; RCT: Randomized controlled trial; VKA: Vitamin K antagonist.

The WOEST,[36] PIONEER AF-PCI,[15] RE-DUAL PCI,[16] and AUGUSTUS[17] studies demonstrated that dual antithrombotic therapy was associated with significantly reduced risk of bleeding events without increasing the risk of ischemic events compared with conventional triple antithrombotic therapy. However, the ENTRUST-AF-PCI study showed that edoxaban-based dual antithrombotic therapy had a similar risk of bleeding and ischemic events compared with triple antithrombotic therapy.[18] The results from the ISAR-TRIPLE study showed no statistically significant difference in the composite endpoint of ischemia and bleeding, endpoint of ischemia, and endpoint of bleeding between patients treated with 6-week and 6-month triple antithrombotic therapy.[37] A recently published meta-analysis on the WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS studies showed that dual antithrombotic therapy had more significant efficacy for the reduction of bleeding risk, while the incidence of major adverse cardiovascular events was quite similar with both regimens.[38] Another meta-analysis showed that, compared with triple antithrombotic therapy, NOAC + P2Y12 receptor antagonist was more effective in reducing the bleeding risk (especially major bleeding and intracranial hemorrhage risk), but increased the risk of stent thrombosis and myocardial infarction. And the risk of all-cause mortality, cardiovascular death, and stroke showed no difference.[39]

Numerous observational cohort studies of OAC in patients with AF and ACS and/or undergoing PCI have been published.[9] Overall, triple antithrombotic therapy is associated with a significantly increased risk of bleeding compared with other antithrombotic regimens. Bleeding risk may be negatively correlated with anticoagulant quality (INR stability).[40] The influence of risk factors for bleeding may be greater than that of combined antithrombotic regimens on the risk of massive bleeding.[41] The incidence of major adverse cardiac and cerebrovascular events is similar among different antithrombotic regimens. For a patient with AF (CHA2DS2-VASc score = 1) undergoing PCI, triple antithrombotic therapy fails to reduce the risk of stroke and/or systemic embolism, but results in an increased risk of bleeding compared with dual antiplatelet therapy (DAPT).[42] Due to the limitations of observational cohort studies, these results should be interpreted with caution.[9] Moreover, triple antithrombotic therapy, including newer, more potent P2Y12 receptor antagonists (prasugrel and ticagrelor), is associated with an increased risk of bleeding.

Antithrombotic regimens

1. Antithrombotic therapy in an acute phase of myocardial ischemia: all patients with AF on OAC should receive oral aspirin at a loading dose of 100 to 300 mg immediately after the occurrence of ACS, followed by a maintenance dose of 75 to 100 mg/day. When the anatomical structure of the coronary artery is known or an emergency such as PCI is planned, pretreatment with P2Y12 receptor antagonists can be considered [Figure 1]. In cases where coronary anatomy is unknown, pretreatment with P2Y12 receptor antagonists should be given until PCI is performed.[9] Compared with clopidogrel, prasugrel and ticagrelor are associated with a greater risk of bleeding despite their higher efficacy.[33,34] Therefore, clopidogrel should be considered as the first choice for P2Y12 receptor antagonists.[9,11] For patients on vitamin K antagonist (VKA) therapy, a 300 mg loading dose of clopidogrel is usually administered [9]; due to limited data, a loading dose of 300 or 600 mg clopidogrel is recommended according to routine clinical practice, no matter with or without NOAC interruption.[9] For patients with a high risk of ischemia/thrombosis (eg, ACS) and a low risk of bleeding, ticagrelor may be a reasonable choice. Ticagrelor is administered with a loading dose of 180 mg followed by a maintenance dose of 90 mg twice per day; the use of aspirin is not recommended (triple therapy should be avoided) if ticagrelor is selected for P2Y12 receptor antagonists.[11] The data on the concurrent use of prasugrel and NOAC therapy is very limited. A study with small sample size showed that triple therapy containing prasugrel was associated with a four-time higher risk of bleeding.[43]

F1
Figure 1:
Process of antithrombotic management of patients with AF requiring OAC during the perioperative period of PCI. AF: Atrial fibrillation; DAPT: Dual antiplatelet therapy; NOAC: Non-vitamin K antagonist oral anticoagulant; NSAID: Non-steroidal anti-inflammatory drug; OAC: Oral anticoagulant; PCI: Percutaneous coronary intervention; PPI: Proton pump inhibitor; SAPT: Single antiplatelet therapy; VKA: Vitamin K antagonist.

For patients on VKA therapy and undergoing coronary angiography and/or PCI, the interruption of VKA is not associated with the reduced risk of bleeding. On the contrary, bridging with heparin while holding VKAs may increase the risk of bleeding. Therefore, the interruption of VKA is usually not recommended, but the INR should be closely monitored preoperatively. Unfractionated heparin should be used intraoperatively for preventing radial artery occlusion, which can possibly reduce the incidence of intraoperative thromboembolic events. As a VKA is being used, low doses (30–50 U/kg) of unfractionated heparin should be administered while closely monitoring activated clotting time (ACT) (maintained at ≥225 s) [Figure 2].[9,29]

F2
Figure 2:
Antithrombotic strategy during the PCI procedure in patients with atrial fibrillation. NOACs are interrupted in a timely manner; NOACs are not interrupted in a timely manner; Dose reduction; §Bivalirudin may be considered as an alternative. A: Aspirin; C: Clopidogrel; H: Heparin; NOAC: Non-vitamin K antagonist oral anticoagulant; NSTE-ACS: Non-ST-segment elevation acute coronary syndrome; O: Oral anticoagulant; PCI: Percutaneous coronary intervention; UFH: Unfractionated heparin; VKA: Vitamin K antagonist.

For patients on NOACs, no interruption of NOACs is required for emergency PCI procedures, but the discontinuation of NOACs before the procedure can be considered for elective PCI. The duration of interruption depends on drugs used and the patient's renal function (usually interrupted 12–24 h before the procedure, and, in the case of dabigatran having a high renal clearance rate, the duration should be prolonged in patients with renal insufficiency), and no heparin bridging is required. Regardless of NOAC interruption, intraprocedural heparin administration should be titrated according to ACT values. Early re-initiation (eg, on the evening of PCI procedure or the next morning) of NOACs after PCI is recommended.[9]

For intraprocedural anticoagulation, bivalirudin (one-time intravenous injection of 0.75 mg/kg, followed by 1.75 mg·kg−1·h−1, maintained until 3–4 h after the procedure) can also be considered as an alternative of heparin, but the use of fondaparinux sodium is not recommended.[9,29] In the BRIGHT study,[44] delayed infusion of high-dose bivalirudin (continuous intravenous infusion of the intraprocedural dose of bivalirudin for 3–4 h after PCI) was administered. Bivalirudin was associated with reduced net adverse events and bleeding risk without increasing the risk of stent thrombosis compared with heparin or heparin in combination with glycoprotein IIb/IIIa receptor inhibitor (GPI).[44] Another meta-analysis showed that the use of bivalirudin was associated with the lowest risk of bleeding compared with heparin or heparin with GPI.[45]

2. Post-procedural and post-discharge antithrombotic therapy: Post-discharge dual antithrombotic therapy with the OAC + P2Y12 receptor antagonist is recommended in most patients in this consensus [Figure 1].[11] The benefits of dual antithrombotic therapy are consistent regardless of the type of stent used.[15–18]

OAC therapy: NOACs are recommended in most patients with AF undergoing coronary stenting compared with VKA, in the case of no contraindication.[9,11] No recommendation exists for the specific NOAC that should preferentially be used due to a lack of the head-to-head comparison of different NOACs.[11] NOACs should be administered according to the available evidence from the RCTs (PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF-PCI studies, etc) [Table 7].[15–18] The RE-DUAL PCI study showed that dual antithrombotic therapy based on dabigatran 110 mg twice daily tended to increase the risk of ischemic events (the difference was, however, not statistically significant, HR = 1.51, 95% CI: 0.94–2.41, P = 0.09) compared with triple therapy.[16] Therefore, dabigatran 150 mg twice daily is recommended in patients with a higher risk of thromboembolism, and 110 mg twice daily is recommended in patients with a higher risk of bleeding. The standard dose of rivaroxaban for preventing stroke is 20 mg once daily in patients with AF. The PIONEER AF-PCI study evaluated rivaroxaban 15 mg once daily + P2Y12 receptor antagonist regimen versus rivaroxaban 2.5 mg twice daily + DAPT regimen in patients with AF and ACS and/or undergoing PCI,[15] and recommended the use of dual antithrombotic therapy containing rivaroxaban 15 mg once daily for preventing stroke.[9,11] For patients using a VKA before PCI, the VKA can be continued after PCI under the premise of adequate INR control and absence of thromboembolism/bleeding complications. For patients with moderate-to-severe mitral stenosis or artificial mechanical heart valve, a VKA should be selected. For patients with severe renal insufficiency (on hemodialysis or Ccr <15 mL/min), VKAs are still considered as the first choice at this stage. The preference target INR is the lower limit of the therapeutic range (2.0–2.5).[9,11] Lifetime anticoagulation therapy should be performed in patients with AF who have an indication for anticoagulation in the case of no contraindication.

Table 7 - Dosing regimens of NOACs in patients with AF and ACS and/or undergoing PCI
Medicinal product Dosage of administration Dose reduction Clinical circumstances requiring dose reduction
Dabigatran 150 mg twice daily (high risk of thrombosis) 110 mg twice daily (high risk of bleeding) Unvalidated
Rivaroxaban 15 mg once daily 10 mg once daily Ccr 30–50 mL/min
Apixaban 5 mg twice daily 2.5 mg twice daily When 2 of the following 3 criteria are satisfied: age ≥80 years, body weight ≤60 kg, or creatinine level ≥133 μmol/L
Edoxaban 60 mg once daily 30 mg once daily Ccr 15–50 mL/min, body weight ≤60 kg, or concurrent use of GPIs
The regimens have been validated by randomized controlled trials. ACS: Acute coronary syndrome; AF: Atrial fibrillation; Ccr: Creatinine clearance rate; GPIs: Glycoprotein IIb/IIIa receptor inhibitors; NOAC: Non-vitamin K antagonist oral anticoagulant; PCI: Percutaneous coronary intervention.

Antiplatelet therapy: For patients in whom dual antithrombotic therapy is considered, aspirin should be administered as an add-on (triple therapy) during the perioperative period of PCI until discharge. For patients with a high risk of ischemia/thromboembolism and a low risk of bleeding, aspirin can be maintained up to 1 month post-procedure after discharge, but rarely beyond 1 month.[11] Discontinuation of antiplatelet therapy 1 year after PCI should be considered in most patients on dual antithrombotic therapy; antiplatelet therapy can be discontinued 6 months after PCI in patients with a low risk of ischemia/thromboembolism and a high risk of bleeding. It may be reasonable to continue dual antithrombotic therapy beyond 1 year in patients with a high risk of ischemia/thromboembolism and a low risk of bleeding [Figure 1]. The choice of antiplatelet drug (aspirin or clopidogrel) should be made by a physician 1 year after PCI, and the continued use of the previous antiplatelet drug is recommended.[11]

Prophylactic doses of OACs for preventing stroke should be continued following the discontinuation of antiplatelet drugs. In cases where low-dose rivaroxaban (15 mg once daily, and in case of a Ccr of 30–50 mL/min, 10 mg once daily) is used in dual antithrombotic therapy, full doses of rivaroxaban (20 mg once daily, in the case of a Ccr of 30–50 mL/min, 15 mg once daily) should be administered after the discontinuation of antiplatelet drugs.[11]

3. Peri-PCI precautions for patients with AF: Multiple factors should be brought into consideration during the perioperative period of PCI in patients with AF [Figure 1]. For example, the indications for PCI and risk assessment should be considered before the procedure, vascular access and selection of stents should be considered during the procedure, and periodical risk assessment should be performed after the procedure. The use of proton pump inhibitors (PPIs) is recommended, and NSAIDs should be avoided.[6,11]

Preprocedural precautions[6,11]: (1) Indications of PCI: The optimization of antithrombotic therapy is quite complicated in patients undergoing PCI who require OAC therapy; therefore, the indications of PCI should be strictly controlled. Eligible patients should be selected for PCI according to the Chinese Guidelines for Percutaneous Coronary Intervention (2016).[29] Revascularization may be considered in patients with ACS and those with stable CAD who still have ischemic symptoms and evidence of a large area of myocardial ischemia under intensified treatment and in whom potential benefits of PCI are judged to outweigh the risks. Conservative antithrombotic therapy is recommended for patients who remain unsure whether to benefit from revascularization. (2) Risk assessment: For patients requiring OAC combined with antiplatelet therapy, a detailed treatment strategy should be formulated according to their characteristics. Risk assessment assists in the screening of patients with a high risk of ischemic, thromboembolic, and bleeding events, and facilitates the determination of intensity and course of antithrombotic therapy. For patients at a high risk of ischemic/thromboembolic and bleeding events, the benefits and risks of each drug should be carefully traded off, and patients’ willingness should be taken into consideration. Patients should be assessed dynamically for the risk of thromboembolism and bleeding in determining the intensity and course of antithrombotic therapy.

Intraprocedural precautions [6,11]: Transradial approach is associated with the reduced risk of bleeding in patients undergoing PCI.[46] Transradial approach is preferred in patients at a high risk of bleeding, including those who require the concurrent use of antiplatelet and anticoagulation therapy. Transradial approach may be safer in patients requiring OAC therapy if anticoagulation cannot be interrupted preprocedurally or the value of INR is within the therapeutic range at the time of PCI. Based on the safety and efficacy profiles, the newer generation of drug-eluting stents is recommended as the first choice.[6] At present, the evidence for biodegradable stents is lacking.

Post-procedural precautions [6,11]: The risk of ischemia and bleeding is high in the early period after PCI and initiation of OAC treatment, which necessitates close monitoring in the first few months after the procedure. Patients treated with VKAs should be monitored more closely (especially in the early stage of treatment) due to widely fluctuating INRs. Renal function should be monitored and, when appropriate, the dose should be adjusted in patients receiving NOACs.[47] Antithrombotic therapy should not be stopped in the case of minor bleeding or ecchymosis, and medical attention should be sought immediately. Patients should be periodically assessed for the risk of ischemia and bleeding to adjust treatment regimens in a timely manner.

It is recommended to use PPIs and avoid NSAIDs post-operatively: PPIs are claimed to reduce GI bleeding, especially in patients receiving combined antithrombotic therapy. The interaction between PPIs and clopidogrel is not a PPI class effect. Interaction is observed only with P450 2C19-inhibiting PPIs (eg, omeprazole and esomeprazole). Therefore, PPIs (eg, pantoprazole and rabeprazole) that do not affect the activity of P450 2C19 should be preferred. NSAIDs should be avoided because they may affect the efficacy of aspirin and increase the risk of bleeding and thrombosis.

Antithrombotic therapy in patients with both stable CAD and AF

Present evidence

AFIRE study was a Japanese RCT conducted in patients with both stable CAD and AF.[48] The results showed that the rivaroxaban monotherapy group (15 mg/day in patients with a Ccr ≥ 50 mL/min, 10 mg/day in patients with a Ccr of 15–49 mL/min) was not inferior to the combined treatment group (rivaroxaban + 1 antiplatelet drug) in the composite endpoint of cardiovascular events or all-cause mortality while the incidence of major bleeding was lower compared with the combined treatment group.

Antithrombotic therapy for patients with both stable CAD and AF

Prophylactic doses of OAC monotherapy for preventing stroke are recommended in patients with both stable CAD and AF who have indications for anticoagulation according to the CHA2DS2-VASc score.[9] Aspirin 75 to 100 mg/day (or clopidogrel 75 mg/day) as an add-on to long-term OAC therapy (eg, rivaroxaban) can be considered in patients with a high risk of ischemia and no high risk of bleeding.[49] NOACs are recommended over VKAs in eligible patients.[9,11]

High risk of ischemia: CAD with diffuse multi-vessel disease accompanied by at least one of the following conditions: (1) diabetes mellitus requiring medical therapy; (2) recurrent myocardial infarction; (3) peripheral arterial disease; and (4) estimated glomerular filtration rate (eGFR) of 15 to 59 mL·min−1·1.73 m−2.

High risk of bleeding: (1) history of cerebral hemorrhage or ischemic stroke; (2) history of other intracranial diseases; (3) recent GI bleeding or anemia caused by GI bleeding; (4) other GI disorders associated with increased risk of bleeding; (5) hepatic insufficiency; (6) beeding tendency or coagulation disorders; (7) old age or frailty; and (8) requiring dialysis or eGFR < 15 mL·min−1·1.73 m−2.

Antithrombotic therapy under special circumstances

Perioperative period of non-cardiac surgery

Anticoagulation therapy

1. Recommendations for patients on warfarin[19]: (1) Preoperative preparation: In the case of surgery with a low risk of bleeding and patients without any risk factor for bleeding (history of major bleeding or intracranial hemorrhage within 3 months, abnormal platelet quality or quantity, history of bridging bleeding, or history of bleeding due to similar surgeries, etc), no interruption of warfarin is required, but the INR should be closely monitored preoperatively to ensure that the INR is within the target therapeutic range (2.0–3.0). In the case of surgery with a high risk of bleeding and/or a patient with risk factors for bleeding, treatment with warfarin should be interrupted preoperatively. The duration of warfarin interruption during the perioperative period mainly depends on the bleeding risk of surgery and the current INR value. The INR should be tested in all patients 5 to 7 days before the surgery. If the surgery requires a completely normal INR, warfarin should be interrupted for 3 to 4 days when the INR is 1.5 to 1.9 and for at least 5 days when the INR ≥2.0. If the INR continues to rise, the procedure should be postponed as far as possible until the INR becomes normal. (2) Post-operative management: Anticoagulation therapy should be restarted 12 to 24 hours after the surgery, depending on the bleeding situation. For surgery with a high risk of bleeding, the restart of anticoagulation can be delayed to 48 to 72 hours after the procedure. Temporary bridging with unfractionated heparin or low-molecular weight heparin can be used until the target INR value is achieved.

2. Recommendation for patients on NOACs[19]: No interruption of NOAC is required for surgery with a low risk of bleeding and manageable bleeding. The duration of NOAC interruption depends on the bleeding risk of the specific surgical procedure [Table 8], renal function, and type of drugs used [Table 9]. Anticoagulation therapy can be restarted a few hours after surgery with a low risk of bleeding and 24 to 72 hours after surgery with a high risk of bleeding.

Table 8 - Bleeding risk classification of surgical and invasive procedures[19]
Class Name of surgery or procedure
Anticoagulant interruption not required Department of Stomatology: extraction of 1 to 3 teeth, periodontal surgery, abscess incision, and implantation of teethDepartment of Ophthalmology: cataract or glaucoma surgery and non-surgical endoscopySuperficial surgeries: abscess incision and small-area skin resection
Low bleeding risk Endoscopy + biopsyProstate or bladder puncture biopsyElectrophysiological examination of supraventricular tachycardiaCatheter ablation of atrial fibrillationCoronary and non-coronary angiography and interventional therapyPacemaker or cardioverter defibrillator implantation (unless anatomically complicated, eg, congenital heart disease)
High bleeding risk Complicated ablation (eg, ventricular tachycardia ablation)Intraspinal or epidural anesthesiaDiagnostic lumbar punctureThoracic surgeryAbdominal surgeryMajor orthopedic surgeryLiver biopsyTransurethral electrosection of prostateRenal biopsy

Table 9 - Preoperative duration of NOAC interruption according to renal function and bleeding risk of surgeries and procedures
Dabigatran Rivaroxaban/Apixaban/Edoxaban


Ccr (mL/min) Low bleeding risk High bleeding risk Low bleeding risk High bleeding risk
≥80 ≥24 h ≥48 h ≥24 h ≥48 h
50–79 ≥36 h ≥72 h ≥24 h ≥48 h
30–49 ≥48 h ≥96 h ≥24 h ≥48 h
15–29 No indications No indications ≥36 h ≥48 h
<15 No indications No indications No indications No indications
Ccr: Creatinine clearance rate; NOAC: Non-vitamin K antagonist oral anticoagulant.

Antiplatelet therapy[50]

For patients receiving aspirin for secondary prevention, drug interruption is not required in most cases during the perioperative period. In the case of closed space surgery (eg, intracranial neurosurgery, posterior chamber intraocular surgery, and spinal canal surgery) or surgery with a high risk of bleeding, drug interruption is required 5 days before the surgery. P2Y12 receptor antagonists (clopidogrel or ticagrelor) are associated with increased bleeding risk during the perioperative period. In patients at low risk of ischemia, P2Y12 receptor antagonists should be interrupted 5 days before the surgery. In the case of a high risk of ischemia, P2Y12 receptor antagonists should be interrupted 5 days before the surgery and switched to intravenous GPI as bridging therapy until 4 hours before the procedure. Antiplatelet therapy should be restarted as soon as possible (preferably within 24 h) after the surgery.

Perioperative period of coronary artery bypass grafting

Anticoagulation therapy: Recommendations are the same as those for non-cardiac surgery[19]; refer to the aforementioned section.

Antiplatelet therapy[51]: (1) Recommendations for the use of aspirin: patients scheduled for CABG should be preoperatively administered with aspirin 100 mg daily. Interruption of aspirin is, in principle, not required before the procedure. Treatment with aspirin (administered via a gastric tube) should be restarted 6 hours after the surgery in patients with stable condition and no bleeding. (2) Recommendations for the use of P2Y12 receptor antagonists: Clopidogrel and ticagrelor should be interrupted for more than 5 days before the surgery, while prasugrel should be interrupted for more than 7 days; for patients requiring emergency care or CABG as soon as possible, clopidogrel and ticagrelor should be interrupted for at least 24 hours to reduce serious bleeding complications. Treatment with P2Y12 receptor antagonists should be restarted as soon as possible (preferably within 24 h) after the surgery.

Perioperative period of catheter ablation for AF

For patients who have taken warfarin or NOACs before the surgery, no interruption of anticoagulation therapy is required during the perioperative period.[13,19] Studies have shown that catheter ablation is safe without interruption of NOACs.[52–55]

At present, no evidence exists about the antiplatelet application during the perioperative period of catheter ablation for AF. Given the fact that catheter ablation for AF is associated with a low risk of bleeding, it is recommended that antiplatelet therapy, if indicated, should not be interrupted during the perioperative period. For patients already on dual antithrombotic therapy (OAC + 1 antiplatelet drug), catheter ablation may be postponed until the antiplatelet drug is withdrawn.

Advanced-age patients (≥75 years)

Patients at an advanced age with both CAD and AF are at a high risk of thromboembolism, and their antithrombotic strategies can be determined according to the risk of ischemia/thrombosis and bleeding [Figure 1].[11] Advanced-age patients often have multiple comorbidities, for example, dementia, an increasing tendency to fall, chronic kidney disease, anemia, hypertension, and diabetes, which may have a greater impact on the patient's quality of life compared with AF-related symptoms.[13] Hepatic and renal dysfunction and concurrent use of multiple drugs may increase the risk of drug interactions and adverse reactions. Enhanced comprehensive management and appropriate anticoagulant dose adjustment are recommended in advanced-age patients.[56]

Patients with renal insufficiency

The risk of both thromboembolism and bleeding increases in patients with renal insufficiency. Dose adjustment according to renal function may be required in patients on NOACs.

Patients with AF presenting with ACS and/or undergoing PCI: The dosage of NOACs in patients with different renal function levels is shown in Table 7 and Figure 3. The results from the meta-analysis showed that warfarin failed to reduce mortality, stroke, or ischemic events but increased the risk of bleeding events in patients with AF on dialysis. However, VKAs are still considered as the first choice for anticoagulation in patients with severe renal insufficiency (on dialysis or Ccr < 15 mL/min).[57] Based on a recent retrospective study,[58] the 2019 AHA/ACC/HRS guidelines for AF proposed that apixaban might be considered in patients with NVAF and end-stage renal disease (Ccr < 15 mL/min) or on dialysis.[20] More recently, a retrospective study also showed that rivaroxaban had similar efficacy to warfarin and significantly reduced the risk of major bleeding by 33% in patients with NVAF and stage 4 to 5 chronic kidney disease or on hemodialysis.[59]

F3
Figure 3:
Recommended doses of NOACs under different renal function statuses in patients with AF and ACS and/or undergoing PCI. 110 mg twice daily in patients with a high risk of bleeding; 2.5 mg twice daily is administered when any two of the following 3 criteria are satisfied: age ≥80 years, body weight ≤60 kg, creatinine ≥133 μmol/L; Other dose reduction criteria may apply (body weight ≤60 kg, concurrent use of glycoprotein IIb/IIIa receptor inhibitors). The gray arrow denotes use with caution (factor Xa inhibitors should be administered at a reduced dose and used with caution in patients with severe renal insufficiency; the efficacy of edoxaban tended to decrease in the presence of increased Ccr. Careful assessment of the risk of thromboembolism and bleeding is required before the initiation of edoxaban in patients with NVAF having high Ccr); the black arrow denotes routine use. ACS: Acute coronary syndrome; AF: Atrial fibrillation; bid: Twice daily; Ccr: Creatinine clearance rate; NOAC: Non-vitamin K antagonist oral anticoagulant; NVAF: Non-valvular atrial fibrillation; PCI: Percutaneous coronary intervention; qd: Once daily.

Patients with both stable CAD and AF: The dosage can be adjusted according to the degree of renal insufficiency when using NOAC monotherapy.[19] Rivaroxaban should be administered at a dose of 20 mg once daily if the Ccr is ≥50 mL/min, 15 mg once daily if the Ccr is 30 to 49 mL/min, and 15 mg once daily with caution if the Ccr is 15 to 29 mL/min. The recommended doses of other NOACs are shown in Figure 3.

Gastrointestinal disorders

The GI tract is the most common site of bleeding in patients with CAD receiving antithrombotic therapy.[60,61] PPIs can reduce the risk of GI bleeding, especially in patients with a history of GI bleeding or peptic ulcer and those concurrently receiving antiplatelet therapy or OAC therapy. For patients receiving aspirin, DAPT, or OACs, the concurrent use of PPIs is recommended in the case of a high risk of GI bleeding. The long-term use of PPIs may increase the risk of hypomagnesemia, but the role of serum magnesium level monitoring remains undefined.[49] In addition, the long-term use of PPIs may lead to hypergastrinemia, impaired vitamin B12 absorption, osteoporosis, fracture, small intestinal bacterial overgrowth, acquired pneumonia, and so forth.[62] However, for patients with clear indications and requiring long-term treatment with PPIs, the use of minimal effective dose is relatively safe, and its benefits far exceed the risks.

Valvular AF

Valvular AF is defined as AF occurring with artificial mechanical valve replacement or moderate-to-severe mitral stenosis. Warfarin is recommended for anticoagulation therapy in patients with valvular AF. See Section “Antithrombotic therapy in patients with AF presenting with ACS and/or undergoing PCI” for the strategy of antiplatelet therapy.

Transition between warfarin and NOACs[47]

Warfarin to NOAC transition: When patients switch from warfarin to NOACs, warfarin should be discontinued first, followed by the close monitoring of INR. NOACs can be administered immediately when the INR is ≤2.0, or preferably the next day when the INR is >2.0 and ≤2.5. The INR should be tested every 1 to 3 days whenever it exceeds 2.5, and NOAC administration should be started only when the aforementioned range is achieved.

NOACs to warfarin transition: When patients switch from NOACs to warfarin, NOACs should be continued (dose remains unchanged except for edoxaban, which reduces to half dose) and should overlap with warfarin usage. Warfarin is initiated with a standard dose that is adjusted according to the INR. The INR should be rechecked after 1 to 3 days if <2.0. NOACs are stopped when an INR ≥ 2.0 is achieved, and then the INR is rechecked 1 day later. The INR should be closely monitored in the first month after the discontinuation of NOAC until the INR stabilization (ie, the INR of 2.0–3.0 for at least 3 consecutive tests).

Management and monitoring of antithrombotic medication use for AF and handling of bleeding

Management and monitoring of antithrombotic medication use for AF[19]

No routine monitoring of coagulating function is required in patients receiving NOACs. Periodical monitoring of INR is required for treatment with warfarin, and the dose should be adjusted accordingly (the target INR value is 2.0–2.5[9,11] for combined antithrombotic therapy and 2.0–3.0 for monotherapy, and time in therapeutic range >65%). The INR should be monitored 1 to 2 times per week during the initial treatment period with warfarin. After stabilization of anticoagulation intensity (ie, the INR is within the therapeutic window for 3 consecutive tests), the INR should be rechecked 1 to 2 times per month. If the INR has remained stable for a prolonged period, the occasional fluctuation of INR does not require the adjustment of warfarin unless it exceeds 3.5; however, a recheck of INR after 2 days is needed. Treatment can be interrupted once or several times in the case of excessive anticoagulation (INR > 4.0), even in the absence of bleeding. The INR usually reduces to the target range 3 days after warfarin interruption.

Handling of bleeding

Medical assessment should include the site of bleeding, time of occurrence, severity, time of the last dose of anticoagulant, and other factors that may affect bleeding severity, for example, liver and renal function, alcoholism, concomitant medication, and a previous history of bleeding. The degree of bleeding is generally classified into mild (epistaxis, small ecchymosis of skin, mild post-traumatic hemorrhage), moderate (gross hematuria, spontaneous large ecchymosis, requiring blood transfusion in absence of hemodynamic disorders), and severe (life-threatening bleeding, including bleeding of critical sites, eg, intracranial hemorrhage, retroperitoneal hemorrhage, and bleeding leading to hemodynamic instability).[19,63]

Mild bleeding: The initiation of supportive treatment is recommended, for example, mechanical compression hemostasis or small surgery hemostasis. For patients on warfarin, drug administration can be delayed or interrupted until the INR reduces to <2.0. Since the half-life of NOACs is short, the coagulating function can be improved 12 to 24 hours after the interruption of treatment.

Moderate bleeding: Fluid infusion and blood transfusion may be required. The cause of bleeding should be immediately identified, followed by the initiation of corresponding treatment. Intravenous injection of vitamin K1 (1–10 mg) can be administered in patients taking warfarin. Oral administration of activated carbon and/or gastric lavage can reduce drug absorption if the latest dose of NOACs is administered within 2 to 4 hours. Dabigatran can be removed by hemodialysis, while the other NOACs are not subject to dialytic elimination.

Severe bleeding: The anticoagulant effect of anticoagulants should be reversed immediately. The infusion of prothrombin complex is always preferred, and the infusion of fresh-frozen plasma can be used in patients taking warfarin. When clinically indicated, platelet transfusion and intravenous injection of vitamin K1 (1–10 mg) may be considered. For patients on NOACs, specific antagonists should be administered to reverse their anticoagulant effect. Idarucizumab is a monoclonal antibody fragment that reverses the anticoagulant activity of dabigatran. This regimen can reverse the anticoagulant effect of dabigatran shortly after administration without any procoagulant effects.[64] Idarucizumab has been approved by the US Food and Drug Administration (FDA), the European Medicines Agency, and the China Drug and Food Administration for clinical use. Andexanet α is a recombinant modified human Xa protein that has no Xa activity. This product can reverse the anticoagulant effect of direct factor Xa inhibitors within a few minutes after administration, thus temporarily increasing procoagulant activity.[65,66] Andexanet α has been approved by the US FDA for reversing the anticoagulant effect of factor Xa inhibitors in the event of life-threatening or uncontrollable bleeding.

Most major bleeding cases have definite etiological or precipitating factors that should be targeted. Anticoagulation therapy often needs to be restarted after bleeding stops. When clinical decision-making is difficult, the multidisciplinary team can assist in facilitating decision-making to balance the risk of recurrence of ischemia/thromboembolism and bleeding, in conjunction with the patient's willingness.[19]

Patient education

It is recommended that patients should be educated with disease knowledge, risk factors, and treatment strategies. The contents of education include knowledge related to CAD and AF, identification of discomfort symptoms, self-rescue after the onset of symptoms, and long-term management. Patients should be trained for self-monitoring of blood pressure and pulse rate. Completely understanding their condition and being less stressed can improve treatment compliance and self-confidence. During the follow-up period, patients should be instructed on how to properly handle the situations of bleeding or recurrence of CAD/AF, and be educated to control the risk factors of bleeding through lifestyle modification.

Consensus statement

The course of triple antithrombotic therapy should be minimized when adequate antithrombotic effects have been achieved, which is followed by dual antithrombotic therapy with OAC plus single antiplatelet drug (preferably clopidogrel 75 mg once daily) in patients with AF and ACS and/or undergoing PCI. The course of triple antithrombotic therapy depends on the risk of ischemia/thromboembolism and bleeding. Prophylactic doses of OAC monotherapy for preventing stroke are recommended in patients with both stable CAD and AF who have indications for long-term anticoagulation.

The expert recommendation for antithrombotic management of patients with both CAD and AF is summarized in Table 10.

Table 10 - Expert recommendation for the antithrombotic management of patients with both CAD and AF
Expert opinion Recommendation class
General management
 Stroke risk assessment using the CHA2DS2-VASc score and bleeding risk assessment using the HAS-BLED score should be performed in patients with AF ++
 Since NOACs are safer than VKAs in triple antithrombotic, dual antithrombotic, or monotherapy, they should be considered as the first choice in the case of no contraindication ++
 VKAs should be selected in patients with moderate-to-severe mitral stenosis or artificial mechanical heart valve ++
 VKAs are considered as the first choice in patients with severe renal insufficiency (on dialysis or Ccr <15 mL/min) ++
 Where VKAs are used, the target INR value is 2.0–2.5 for combined antithrombotic therapy and 2.0–3.0 for monotherapy, and the time in the TTR is >65% ++
 Use of PPIs should be considered in patients on OAC + antiplatelet therapy to reduce the risk of gastrointestinal bleeding ++
 Long-term anticoagulation therapy should be performed in patients with a CHA2DS2-VASc score ≥2 (male)/3 (female) ++
 Anticoagulation therapy should also be performed in patients with good compliance and a CHA2DS2-VASc score of 1 (male)/2 (female) +/±
Antithrombotic therapy in patients with AF and ACS and/or undergoing PCI
 Patients on anticoagulation therapy who are scheduled for PCI can be pretreated with the same antiplatelet therapy as patients without AF ++
  • In cases where the severity of the patient's CAD is unknown, pretreatment with P2Y12 receptor antagonists should be delayed +/±
 The interruption of VKAs is usually not required, but the INR should be checked preoperatively in patients on VKAs and undergoing coronary angiography and/or PCI +/±
 No interruption of NOACs is required in patients on NOACs who require emergency PCI procedures +/±
 Preoperative interruption of therapy can be considered in patients on NOACs who require elective PCI procedures. The duration of treatment interruption depends on drugs used and renal function +/±
  • Treatment is usually interrupted 12–24 h before the procedure and, in case of dabigatran that has a high renal clearance rate, the duration of preoperative interruption of therapy should be prolonged in patients with renal insufficiency +/±
  • NOAC therapy should be restarted early (eg, on the evening of PCI procedure or the next morning) after PCI +/±
 Intraprocedural use of low doses (30–50 U/kg) of unfractionated heparin and dose adjustment according to ACT values are required in patients on VKA or NOAC treatment undergoing PCI, irrespective of anticoagulation interruption +/±
 For intraprocedural anticoagulation, bivalirudin (one-time intravenous injection of 0.75 mg/kg, followed by 1.75 mg·kg−1·h−1, maintained until 3–4 h after the procedure) can be considered as an alternative to unfractionated heparin ++
 Triple antithrombotic therapy is recommended during initial hospitalization among patients with AF presenting with ACS and/or undergoing PCI ++
  • For patients with a high risk of ischemia/thrombosis and a low risk of bleeding, aspirin (eg, triple therapy) can be continued up to 1 month post-procedure after discharge, but rarely beyond 1 month +/±
  • Ticagrelor and prasugrel should be avoided in the triple therapy
 Post-discharge dual antithrombotic therapy (OAC + P2Y12 receptor antagonist) can be administered in most patients ++
  • Clopidogrel is considered as the first choice for P2Y12 receptor antagonists ++
  • For patients with a high risk of ischemia and a low risk of bleeding, ticagrelor may represent a reasonable choice +/±
  • Prasugrel should be avoided in the combined antithrombotic therapy
 For patients using VKAs before PCI, continued use of VKAs after stenting is appropriate under the premise of adequate control of INR and absence of thromboembolism/bleeding complications +/±
 Antiplatelet therapy is discontinued after 1 year in most patients
  • Earlier discontinuation of antiplatelet therapy (eg, after 6 months) should be considered in patients with a low risk of ischemia or a high risk of bleeding +/±
  • Prolonged single antiplatelet therapy (>1 year) should be considered in patients with a high risk of ischemia and a low risk of bleeding +/±
 Prophylactic doses of OACs for preventing stroke should be continued following the discontinuation of antiplatelet therapy ++
  • In cases where low-dose rivaroxaban (15 mg once daily, and in the case of a Ccr of 30–50 mL/min, 10 mg once daily) is used in dual antithrombotic therapy, 20 mg once daily in the case of a Ccr ≥50 mL/min, 15 mg once daily in the case of a Ccr of 30–49 mL/min and 15 mg once daily with caution in the case of a Ccr of 15–29 mL/min should be administered after discontinuation of antiplatelet therapy +/±
Antithrombotic therapy in patients with both stable CAD and AF
 Prophylactic doses of OAC monotherapy for preventing stroke are recommended in patients with indications for anticoagulation according to CHA2DS2-VASC score ++
 Combined use of OAC and antiplatelet therapy is not advocated unless patients have a very high risk of coronary events and a low risk of bleeding
 Single antiplatelet therapy with aspirin 75–100 mg/day (or clopidogrel 75 mg/day) as an add-on to long-term OAC therapy (eg, rivaroxaban) can be considered in patients with a high risk of ischemia and no high risk of bleeding +/±
ACS: Acute coronary syndrome; ACT: Activated clotting time; AF: Atrial fibrillation; CAD: Coronary artery disease; Ccr: Creatinine clearance rate; INR: International normalized ratio; NOAC: Non-vitamin K antagonist oral anticoagulant; OAC: Oral anticoagulant; PCI: Percutaneous coronary intervention; PPI: Proton pump inhibitor; TTR: Time in therapeutic range; VKA: Vitamin K antagonist; ++: The treatment or procedure should be performed; +/±: The treatment or procedure can be performed; –: The treatment or procedure should not be performed.

Funding

This work was supported by the National Key Research and Development Projects (No. 2018YFC1312502) to Shulin Wu.

Author Contributions

Authoring expert: Peng Qu (The Second Hospital of Dalian Medical University), Shaowen Liu (Shanghai General Hospital), Changsheng Ma (Beijing Anzhen Hospital, Capital Medical University), Yumei Xue (Guangdong Provincial People's Hospital), and Xinjun Lei (First Affiliated Hospital of Xi’an Jiaotong University)

Core members of expert group: (sorted by surname Pinyin): Yaling Han (General Hospital of North Theater Command), Lan Huang (Xinqiao Hospital Army Medical University), Shuyan Li (The First Bethune Hospital of Jilin University), Yi Li (General Hospital of North Theater Command), Shaowen Liu (Shanghai General Hospital), Changsheng Ma (Beijing Anzhen Hospital, Capital Medical University), Xiaoyong Qi (Hebei General Hospital), Peng Qu (The Second Hospital of Dalian Medical University), Zulu Wang (General Hospital of North Theater Command), Shulin Wu (Guangdong Provincial People's Hospital), and Zuyi Yuan (First Affiliated Hospital of Xi’an Jiaotong University)

Members of expert group: (sorted by surname Pinyin): Jiyan Chen (Guangdong Provincial People's Hospital), Guosheng Fu (Sir Run Run Shaw Hospital Zhejiang University School of Medicine), Chuanyu Gao (Fuwai Central China Cardiovascular Hospital), Wei Gao (Peking University Third Hospital), Shaobin Jia (General Hospital of Ningxia Medical University), Chenyang Jiang (Sir Run Run Shaw Hospital Zhejiang University School of Medicine), Xinjun Lei (First Affiliated Hospital of Xi’an Jiaotong University), Yigang Li (Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Qiming Liu (The Second Xiangya Hospital of Central South University), Xuebo Liu (Tongji Hospital of Tongji University), Yuyang Liu (Beijing Anzhen Hospital, Capital Medical University), Dayuan Lou (The Second Hospital of Dalian Medical University), Zhibing Lu (Zhongnan Hospital of Wuhan University), Yongbai Luo (First Affiliated Hospital of Xi’an Jiaotong University), Yihong Sun (China-Japan Friendship Hospital), Yida Tang (Fuwai Hospital Chinese Academy of Medical Sciences), Yongjian Wu (Fuwai Hospital Chinese Academy of Medical Sciences), Yawei Xu (Shanghai Tenth People's Hospital), Yumei Xue (Guangdong Provincial People's Hospital), Lixia Yang (No. 920 Hospital of the PLA Joint Logistics Support Force), Xinchun Yang (Beijing Chaoyang Hospital, Capital Medical University), Yanmin Yang (Fuwai Hospital Chinese Academy of Medical Sciences), Yuehui Yin (The Second Affiliated Hospital of Chongqing Medical University), Jinqing Yuan (Fuwai Hospital Chinese Academy of Medical Sciences), Ping Zhang (Beijing Tsinghua Changgung Hospital), Ruiyan Zhang (Ruijin Hospital Shanghai Jiaotong University School of Medicine), Shuyang Zhang (Peking Union Medical College Hospital Chinese Academy of Medical Sciences), and Zheng Zhang (The First Hospital of Lanzhou University)

Conflicts of Interest

None.

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Keywords:

Antithrombotic management; Atrial fibrillation; Coronary artery disease

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