Management of antithrombotic

therapy after bleeding in

patients with coronary artery
disease and/or atrial fibrillation
Jasmina Jovanoski
Ohrid 24.3.2017
• Bleeding is a frequent complication of the
management of patients with coronary
artery disease (CAD), especially those
presenting with acute coronary syndromes
(ACS) or undergoing percutaneous
coronary intervention (PCI), and of
patients with atrial fibrillation (AF).
• major bleeding of 1–8% at 30 days in ACS
patients, 
• 2–5% per year in patients with AF treated
with oral anticoagulants (OACs)
• Patients who are more likely to suffer from
bleeding complications - tend to be at
higher risk of thrombotic events
• Discontinuation of antithrombotic drugs -
increased rate of thrombotic events
(progressive recovery of platelet function
and coagulation activity)
• Bleeding may provoke prothrombotic
responses
• Balancing the risks of further bleeding vs.
potentially fatal thrombotic events is critical
• When the thrombotic risk is higher than
the risk of recurrent bleeding - continuing
antithrombotic therapy.
• When thrombotic risk is in equipoise with
bleeding risk - only brief or temporary
interruption of antithrombotic therapy.
• When bleeding risk outweighs thrombotic
risk - considering, on a case to case basis,
reducing the number and/or dose of
antithrombotic drug(s). 
Antiplatelet therapy after
extracranial bleeding
 Patients with a recent acute coronary
syndrome and/or percutaneous coronary
intervention (<12 months)

• The risk of stent thrombosis increases with

longer time off treatment, particularly more
than 5 days, and if treatment is stopped
within the 1st month after the procedure.
• newer-generation (everolimus- or
zotarolimus-eluting) drug-eluting stents
(DES) support shortening DAPT duration
in patients at high risk of bleeding
• If major bleeding occurs after 3–6 months of
DAPT, these studies lend support to
discontinuing the P2Y 12 inhibitor and continuing
aspirin alone, particularly in patients without a
prior history of ACS
•  risk of stent thrombosis is lowest with the
newest generation DES, the thrombotic risk
appears higher with the new bioresorbable
vascular scaffolds (BVS)
•  clopidogrel may be used as P2Y12 inhibitor
after bleeding has occurred during treatment
with prasugrel or ticagrelor, as soon as re-
initiation of antiplatelet therapy is possible. 
Patients with stabilized coronary artery disease
(>12 months after percutaneous coronary
intervention or acute coronary syndromes)
• single antiplatelet therapy prescribed for
secondary prevention in stable CAD patients
should be reinitiated within a few days after
bleeding.
• cessation of, or non-adherence to, aspirin were
associated with a three-fold higher risk of major
adverse cardiac events compared to its
continued use , the risk was magnified in
patients with coronary stents.
Resuming antiplatelet therapy
after gastrointestinal bleeding
 Consensus summary on antiplatelet
therapy after extracranial bleed

1. For patients at high or very high

thrombotic risk (ACS or coronary stenting
<30 days) who develop minor or major
bleeding - continuation of low-dose aspirin
without interruption. Restarting of the
second antiplatelet agent should be
considered as soon as possible after
stabilization.
• 2. For patients at moderate thrombotic risk (ACS
or PCI with a second generation DES 1–12
months ago) who develop minor or major
bleeding - resumption of low-dose aspirin as
soon as bleeding is controlled (within 3 days)
Restarting a second antiplatelet agent should be
considered if thrombotic risk outweighs recurrent
bleeding risk.
• 3. For patients who develop bleeding while on
DAPT within 3 months of new generation DES
implantation - we suggest resuming DAPT up to
3 months. If patients develop bleeding more than
3 months after new generation DES implantation
and remain at risk of recurrent bleeding -
resumption of only one antiplatelet agent (either
aspirin or clopidogrel).
• 4. Addition of a PPI is recommended in all
cases of upper GI bleeding. 
• 5.PPI should also be used in patients on
DAPT at higher than average risk of GI
bleeds. 
• 6. The pharmacodynamic interaction
between PPIs (especially omeprazole) and
clopidogrel has not so far been clearly
associated with worse clinical outcome,
but it is preferred to use PPIs with weaker
CYP2C19 inhibition (e.g. pantoprazole)
 Oral anticoagulant therapy after
extracranial bleeding
• in the presence of a clear indication, VKA
therapy should be resumed within 1 week
following major GI bleeding
• when (re)starting a NOAC, renal function should
be carefully assessed and monitored to avoid
drug accumulation.
• if an antidote (idaruzicumab) has been used to
reverse the anticoagulant effect of a NOAC, it is
suggested to restart OAC as soon as possible,
preferably within 3–4 days if the individual
bleeding risk allows.
 Resuming antithrombotic therapy in patients
with an indication for both antiplatelets and
oral anticoagulant
• stopping either aspirin or clopidogrel for major bleeding
during triple oral antithrombotic therapy.  
• VKA vs. NOAC - either can be used in combination with
antiplatelet therapy.
• avoiding the use of prasugrel or ticagrelor as part of
triple therapy
• When NOACs are combined with antiplatelet drugs, the
lowest effective dose for stroke prevention should be
used, meaning dabigatran 110 mg bid (rivaroxaban 15 
mg od, apixaban 2.5 mg bid, or edoxaban 30 mg od, only
when criteria for dose lowering are present)
• When PCI-treated patients with non-valvular AF
develop bleeding during triple oral antithrombotic
therapy - stopping either aspirin or clopidogrel
• In patients who develop major bleeding on
double therapy (OAC plus single antiplatelet),
discontinuation of the antiplatelet agent
• We suggest DAPT alone (without OAC) for 1
year after ACS/PCI when a patient with non-
valvular AF and a low risk of stroke
(CHA 2 DS 2 -VASc  1 for men, 2 for women)
develops bleeding during triple or double
antithrombotic therapy.
 Antithrombotic therapy after
intracranial haemorrhage
• ICH is one of the most feared
complications of OAC
• Whether and when to restart OAC after an
ICH should be decided on an individual
basis, depending on the patient’s
thrombotic risk and the risk of recurrent
bleeding
• In the absence of mechanical valves,
NOACs - preferable to warfarin after ICH