Difficult situations in anticoagulation after stroke George Ntaios University of Thessaly, Larissa/Greece

Disclosures Scholarships: European Stroke Organization; Hellenic Society of Atherosclerosis. Honoraria: Medtronic; Quintiles; Boehringer-Ingelheim. Speaker fees/Advisory Boards: Sanofi; Boehringer-Ingelheim; Galenica; Elpen; Bayer; Winmedica; BMS/Pfizer; Amgen Research support: European Union (Horizon 2020); BMS/Pfizer (ERISTA) Most relevant disclosure

AF on VKA (INR:1.9) Very good recovery Clinical case vignette: an 80-year-old patient with a history of hypertension, diabetes mellitus, congestive heart failure, and atrial fibrillation on acenocoumarol presents with a right putaminal hemorrhage. International normalized ratio at admission is 1.9 and brain computed tomography (CT) reveals extensive leukoaraiosis. The patient has a good recovery with a modified Rankin scale score of 2 at discharge. Would you restart anticoagulation?

Restart OAC after AF/OAC-related ICH Nielsen et al. Circulation 2015

Restart OAC after AF/OAC-related ICH Nielsen et al. Circulation 2015

Restart OAC after AF/OAC-related ICH !?!?!?!! Nielsen et al. Circulation 2015

We need to individualize

Bleeding vs. thromboembolic risk

Prognostic scores? HAS-BLED CHA2DS2-VASC2 CHADS2

Estimate bleeding risk in AF: HAS-BLED HAS-BLED Risk Criteria Score Hypertension 1 point Abnormal renal/liver tests 1-2 point Stroke Bleeding Labile INR 2 points Elderly 1 points Drugs or alcohol 1-2 points Risk of major bleeding depends on patient factors (HAS-BLED – border registry).

Estimate embolic risk in AF: CHA2DS2VASc CHA2DS2Vasc Risk Criteria Score Congestive heart failure 1 point Hypertension Age >75 years 2 point Diabetes mellitus Stroke/ transient ischemic attack 2 points Vascular disease Age 65-74 Female sex 1 Estimate thromboembolic risk in AF if not anticoagulated  chads, chadsvasc scores, show them. But they were not validated in the perioperative period

Well, sorry…. CHA2DS2Vasc Risk Criteria CHADS2 Risk Criteria HAS-BLED Risk Criteria Congestive heart failure Labile INR Hypertension Diabetes mellitus Bleeding Stroke/ transient ischemic attack Stroke Vascular disease Abnormal renal/liver tests Age >75 years Elderly Age 65-74 Drugs or alcohol Female sex Estimate thromboembolic risk in AF if not anticoagulated  chads, chadsvasc scores, show them. But they were not validated in the perioperative period

Cerebral microbleeds

Cerebral microbleeds & ICH risk Charidimou et al. Stroke 2013

Cerebral microbleeds & ischemic stroke risk Charidimou et al. Stroke 2013

If you anticoagulate, choose a low-dose NOAC Ruff et al. Lancet 2013

Anticoagulation after AF-stroke: how soon (or late?) So, let us discuss about few of them using some patient examples… This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

The 1-3-6-12 rule TIA  1 day Small infarct  3 days Moderate infarct 6 days Large infarct  12 days Now, there are two points which we could keep in mind to make our life easier and the life of our patients safer. Recently the EHRA provided an expert-opinion rule, i.e. the 1-3-6-12 rule, which means that ….. But we need to keep in mind that this is not supported yet by high quality data.

NOACs could be the answer? The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin! Ruff et al. Lancet 2013

The ALESSA score Age Ischemic index LESion >1.5 cm  1 point ≥80 years  2 points 70-79 years  1 point Ischemic index LESion >1.5 cm  1 point Severe Atrial enlargement  1 point The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin! Paciaroni, in preparation

The ALESSA score The second point is that perhaps in these cases, a NOAC, rather than a vitamin K antagonist, is the best choice that you could make. Why? Because as we all know, the NOACs are so much safer than antivitamin-Ks, and this high safety profile is exactly what you need in the acute phase where the bleeding risk of the patients is higher. And perhaps, among all NOACs, you would like to choose dabigatran, because as we know, it is associated with the lowest risk for hemorrhagic stroke in secondary stroke prevention, which is close to 80% compared to warfarin! Paciaroni, in preparation

SHORT CASE REPORT - Kouklis

Bridging VKA with LMWH Explain bridging Rio-Antirio bridge

“ Do not bridge !!!! ” https://bridge.dcri.duke.edu/ ALSO: PERIOP-2 in Canada (https://clinicaltrials.gov/ct2/show/NCT00432796) Douketis. N Engl J Med 2015

“ Do not bridge !!!! ” https://bridge.dcri.duke.edu/ ALSO: PERIOP-2 in Canada (https://clinicaltrials.gov/ct2/show/NCT00432796) Douketis. N Engl J Med 2015

Pre-operative discontinuations of NOACs Sumary slide – Heidbuchel Heidbuchel. European Heart Journal 2013

Sumary slide – Heidbuchel Heidbuchel. European Heart Journal 2013

Ischemic stroke in anticoagulated patient So, let us discuss about few of them using some patient examples… This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

Acute endovascular treatment - thrombectomy Andexanet produced near complete normalization of all coagulation parameters measured within 2 minutes of completion of infusion. Vanacker, Stroke 2016

INR >1.5 Ischemic stroke in VKA-treated patient So, let us discuss about few of them using some patient examples… This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

Ischemic stroke in dabigatran-treated patients So, let us discuss about few of them using some patient examples… This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

Idarucizumab: a reversal agent for dabigatran Thrombin Dabigatran Idarucizumab

Idarucizumab: a reversal agent for dabigatran

Time after end of infusion (hours) Idarucizumab: a reversal agent for dabigatran 70 65 60 55 dTT (s) 50 45 40 35 30 –2 2 4 6 8 10 12 24 36 48 60 72 Time after end of infusion (hours)

Arterial occlusion accessible by mechanical thrombectomy in CTA ? No Arterial occlusion accessible by mechanical thrombectomy in CTA ? Yes Within 4.5 hours after onset ? Last intake of Dabigatran not known Yes Within 6 hours after onset? aPTT/dTT/TT prolonged Last intake of Dabigatran <24 hours Yes No Yes No Yes No Idarucizumab No attempt for recanalization Mechanical thrombectomy IV rt-PA

Ischemic stroke in dabigatran-treated patients

Ischemic stroke under Xa inhibitors So, let us discuss about few of them using some patient examples… This was the CT angiograpjy of an AF patient who was not anticoagulated. As you see, there is…..

Andexanet: an antidote for Xa inhibitors

Ciraparantag: an antidote for … all Andexanet produced near complete normalization of all coagulation parameters measured within 2 minutes of completion of infusion. Ansell et al. NEJM2014

Arterial occlusion accessible by mechanical thrombectomy in CTA ? No Arterial occlusion accessible by mechanical thrombectomy in CTA ? Yes Within 4.5 hours after onset ? Last intake of Xa inhibitors not known Yes Within 6 hours after onset? Anti-Xa assays prolonged Last intake of Xa inhibitors <24-48 hours Yes No Yes No Yes No Andexanet alpha / ciraparantag No attempt for recanalization Mechanical thrombectomy IV rt-PA

Take-home messages Restart anticoagulants after ICH? How soon OAC after IS? Do not bridge! Ischemic stroke in anticoagulated patient?