Leeds Teaching Hospitals guidance on anti-platelet therapy in patients receiving oral anti-coagulants for non-valvular atrial fibrillation (NVAF) undergoing Percutaneous Coronary intervention (PCI)

• Patients with NVAF undergoing Elective PCI 
  • Information for Primary Care
• Patients with NVAF presenting with Acute Coronary Syndrome (ACS)
  • Information for primary care
• General Points
• Table 1. Recommendations for discontinuation of NOACs prior to elective PCI

Patients with NVAF undergoing Elective PCI  

• In patients with stable coronary disease taking warfarin, consider switching therapy to a Direct Oral Anticoagulant (DOAC) in advance of procedure unless contraindicated, on interacting medicines, creatinine clearance <30mL/min [see general points below], or strong patient preference to continue warfarin. Involve patients in the decision. Consider a DOAC with clinical evidence for lower bleeding risk than warfarin in patients with NVAF undergoing PCI [e.g. apixaban, dabigatran or rivaroxaban - see general points below].
• If warfarin is preferred, omit warfarin for 2 days before and on the day of the procedure. INR to be checked on admission. If warfarin therapy is to be continued after the procedure, resume therapy on the same day or next day at the discretion of the operator. Note that patients taking warfarin for metallic heart valves should not interrupt therapy, but dose should be adjusted aiming for target INR 2.5 on day of procedure
• In stable patients receiving a DOAC, discontinue pre-procedure in accordance with LTHT Guidance: ‘Peri-operative Management of New Oral Anticoagulants for patients undergoing elective procedures’ (summarised in Table 1).  Restart DOAC within 24h following the procedure as soon as vascular access site is secure.
• In patients not already prescribed dual anti-platelet therapy, load with aspirin 300mg and clopidogrel 300mg the evening before the procedure.
• Continue clopidogrel and oral anticoagulant (OAC) for 12 months following PCI.
• Further aspirin treatment is at the operator’s discretion but, if continued, should be given for as short a period as possible (usually 1 week) to minimise risk of bleeding. In most cases OAC and clopidogrel therapy is sufficient in patients with stable coronary disease.
• After 12 months, stop clopidogrel and continue OAC alone unless at high risk of future coronary events (e.g. prior stent thrombosis on adequate anti-platelet therapy, stenting of last remaining coronary artery, diffuse multivessel disease – especially in patients with diabetes, creatinine clearance <60mL/min, at least three stents implanted, bifurcation with two stents implanted, total stent length >60mm, treatment of chronic total occlusion).
• The plan of the anti-platelet + OAC therapy including the intended durations of each agent should be communicated with patient and clearly stated on the discharge advice notification. 

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Information for Primary Care

• Advice for management of OAC and anti-platelet therapy will be provided to patients at the pre-admission clinic before elective PCI
• Patients prescribed warfarin will usually be advised to omit warfarin for two days before elective PCI.
• Patients prescribed DOACs, will be advised to stop treatment before the procedure see table 1.
• Detailed advice on antiplatelet and OAC therapy will be provided on discharge.
• In most patients we recommend continuing clopidogrel and OAC for 12 months following PCI.
• After 12 months the patient should continue only on OAC unless advised otherwise.
• The plan may sometimes be altered on an individual patient basis. This will be communicated on discharge.

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Patients with NVAF presenting with Acute Coronary Syndrome (ACS)

• In ACS patients taking warfarin or a DOAC for NVAF, discontinue treatment on admission.
• Prescribe fondaparinux to continue until procedure:
• Defer starting fondaparinux until INR ≤2.0 in patients who were taking warfarin.
• Defer starting fondaparinux for 12 hours after the last dose of DOAC in patients taking a TWICE daily DOAC.
• Defer starting fondaparinux for 24 hours after the last dose of DOAC in patients taking a ONCE daily DOAC.
• i.e. start fondaparinux when next dose of DOAC would have been due
• Prescribe aspirin (300mg loading then 75mg daily) and clopidogrel (600mg loading then 75mg daily) on admission.
• Do not routinely prescribe ticagrelor or prasugrel in patients with NVAF who require OAC.
• Following procedure and once vascular access site haemostasis is secure, initiate a DOAC regardless of prior anticoagulation strategy (unless contraindicated, on interacting medicines, creatinine clearance <30mL/min [see general points below] or strong patient preference to continue warfarin). Involve patient and consider patient-preference in the decision to switch from warfarin to DOAC. Consider a DOAC with clinical evidence for lower bleeding risk in patients with NVAF undergoing PCI [e.g. apixaban, dabigatran or rivaroxaban - see general points below]
• Triple therapy with DOAC (or warfarin if a DOAC is not appropriate) + aspirin 75mg daily + clopidogrel 75mg daily should usually be continued for one week (maximum four weeks) after PCI, followed by DOAC (or warfarin if a DOAC is not appropriate) and clopidogrel 75mg daily for one year. Add gastric protection as appropriate – see below.
• DOAC (or warfarin if a DOAC is not appropriate) + clopidogrel 75mg (without further aspirin) may be used at operator’s discretion if bleeding risk is considered high.
• After 12 months, stop clopidogrel and continue OAC alone unless at high risk of future coronary events (e.g. prior stent thrombosis on adequate anti-platelet therapy, stenting of last remaining coronary artery, diffuse multivessel disease – especially in patients with diabetes, creatinine clearance <60mL/min, at least three stents implanted, bifurcation with two stents implanted, total stent length >60mm, treatment of chronic total occlusion).
• The plan of the antiplatelet + OAC therapy including the intended duration of each agent should be communicated with patient and clearly stated on the discharge advice notification. 

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Information  for Primary Care

• Most patients with ACS and NVAF will be discharged on triple therapy (Aspirin + Clopidogrel + DOAC) for the shortest acceptable duration to minimize risk of bleeding.
• Detailed advice on antiplatelet and OAC therapy will be provided on discharge.
• However, generally we recommend stopping aspirin 1-4 weeks post procedure and stopping clopidogrel 12 months post procedure. The OAC should continue indefinitely.
• In some patients at higher risk of recurrent coronary events we may recommend continuing clopidogrel alongside the OAC indefinitely.
• Patients with NVAF who have undergone PCI for ACS will usually be discharged on a DOAC in preference to warfarin unless contraindicated.
• The plan may sometimes be altered on an individual patient basis. This will be communicated on discharge.

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General points

• These recommendations are for guidance only and may need to be adapted on an individual patient basis. They apply only to patients with NVAF scheduled for PCI. Patients receiving OAC for other indications (VTE, metallic valves etc) should be considered on a case by case basis.
• A clear plan for the type and duration of OAC and anti-platelet therapy must be documented by the operator at the time of PCI, discussed with the patient and /or carer and communicated to the GP on the discharge notification
• Consider DOAC in preference to warfarin when initiating OAC in patients with NVAF who require PCI. Please discuss and agree with patient adopting a shared-decision making approach.
• For new initiations, consider a DOAC with clinical evidence for reduced bleeding compared to warfarin in patients with NVAF undergoing PCI, e.g. apixaban, dabigatran or rivaroxaban.
• Apixaban 5mg twice daily in addition to a P2Y12 inhibitor and aspirin or placebo was used in AUGUSTUS. The dose of apixaban was reduced to 2.5mg twice daily in patients with two or more of the following dose-reduction criteria: at least 80 years of age, weight of no more than 60 kg, or creatinine level of at least 133 μmol/L)
• Dabigatran 110mg twice daily or 150mg twice daily in addition to clopidogrel or ticagrelor for at least 12 months was used in RE-DUAL PCI. Consider 110mg dose in patients aged >75 years, with CrCl 30-50mL/min, with gastritis, oesophagitis, gastroesophageal reflux or history of bleeding.
• Rivaroxaban 15mg daily (10 mg daily for patients with creatinine clearance 30 – 49 mL/min) in addition to a P2Y12 inhibitor for a maximum of 12 months was used in PIONEER AF-PCI. Resume treatment at 20mg daily (15mg daily for patients with creatinine clearance 30 – 49 mL/min) after discontinuation of P2Y12 inhibitor.
• Edoxaban 60mg once daily (30mg once daily if creatinine clearance 15–50 mL/min, bodyweight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors) did not to demonstrate superiority for bleeding events compared to a warfarin-based regime in ENTRUST-AF PCI.
• Note that some DOACs require dose reduction in patients with CrCl<50mL/min. DOACs should be used with caution and some DOACs (dabigatran) are not indicated in patients with CrCl 15 -30mLs/min. Please refer to SPCs before prescribing DOACs to patients with kidney disease.
• Patients with a CrCl 15 -30mLs/min who are newly started on a DOAC which is licensed for use in this level of renal impairment should be referred to the DOAC clinic as monitoring may be required.
• A CrCl calculator is available at: http://nww.lhp.leedsth.nhs.uk/Calculators/Renal/
• Do not prescribe DOACs to patients taking interacting drugs such as carbamazepine, phenobarbital, phenytoin, rifampicin, protease inhibitors, antifungals – see SPCs for detailed information.
• Consider use of drug-eluting coronary stents with evidence of safety in patients at high bleeding risk in patients with NVAF who require OAC.
• Prescribe gastro-protection with a proton pump inhibitor in all patients receiving an OAC in combination with anti-platelet drugs.

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Table 1. Recommendations for discontinuation of DOACs prior to elective PCI

Creatinine Clearance should be estimated using an appropriate calculator based on the Cockcroft-Gault formula – e.g. http://nww.lhp.leedsth.nhs.uk/Calculators/Renal

Adapted from ‘LTHT Guidelines for the Peri-operative Management of New Oral Anticoagulants for Patients Undergoing Elective Procedures’. Issue date 22.02.16. Accessible at: http://nww.lhp.leedsth.nhs.uk/common/guidelines/anticoagulation.asp