Γεώργιος Ντάιος Παθολογική Κλινική Πανεπιστημίου Θεσσαλίας Κλινικές περιπτώσεις με μη βαλβιδική κολπική μαρμαρυγή

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)

Our patient ♂, 89yrs Arterial hypertension on amlodipine HbA1c: 7.9% on metformin eGFR: 44ml/min Diastolic heart failure Atrial fibrillation on vit-K antagonist Frequent INR monitoring Frequent dose adjustments Drug and drug interactions Food and drug interactions

“Too old for this? “ “Too old for this? “

Primary endpoint: Stroke/SE HR : 0.80 (0.63–1.02) Months from randomization 2.85%/yr 2.29%/yr Estimated cumulative probability of stroke/SE (%) Warfarin ≥75 years Rivaroxaban ≥75 years

“Too old for this? “ “Too old for this? “ Age ≥75 years (%/year) RivaroxabanWarfarin Major bleeding ICH

“What about my renal failure? “ “What about my renal failure? “

Primary endpoint: Stroke/SE %/yr 2.3%/yr HR: 0.84 (0.57–1.23) Cumulative event rate (%) Days from randomization Warfarin CrCl 30–49 mL/min Rivaroxaban CrCl 30–49 mL/min

“What about my renal failure? “ “What about my renal failure? “ Events (%/year) HR 0.55 (95% CI 0.30–1.00) HR 0.39 (95% CI 0.15–0.99) Warfarin Rivaroxaban 15 mg OD

“What about my diabetes? “ “What about my diabetes? “

HR: 0.74 (0.54–1.01) Days from randomization Cumulative event rate Primary endpoint: Stroke/SE 1.59%/yr 2.15%/yr Warfarin with DM Rivaroxaban with DM

“What about my diabetes? “ “What about my diabetes? “

“What about my heart failure? “ “What about my heart failure? “

Primary endpoint: Stroke/SE (ITT) HR: 0.91 (0.74–1.13) Rivaroxaban with HF Days from randomization Cumulative event rate (%) %/yr 1.90%/yr Warfarin with HF

“What about my heart failure? “ “What about my heart failure? “ With HF (%/year) Riva.Warf. Major/NMCR bleeding Haemorrhagic stroke Intracranial haemorrhage

“OK, but too many co-morbidities…“ “OK, but too many co-morbidities…“ ≤123–6CHADS 2 score

“OK, but too many co-morbidities…“ “OK, but too many co-morbidities…“

“OK, but does it really work ?“ “OK, but does it really work ?“

CHADS 2 ROCKET AF3.5 XANTUS2.0 XANTUS vs. ROCKET AF

Bleeding events per CHADS 2 group Mean CHADS 2 score Major bleeding event rate/year Randomized clinical trial ROCKET AF 1* n= % 3.0% 2.9% 2.1% Prospective registry Dresden NOAC 2# n= Retrospective database US DoD PMSS 3‡ n=27,467 Observational study XANTUS 4* n=6784

“OK, but which dose?“ “OK, but which dose?“

Switch from VKA to NOACs Heidbuchel et al. Europace 2015

Interventions in anticoagulated patients: not rare

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

Postoperative resumption of NOACs Heidbuchel. European Heart Journal 2013

Acute endovascular treatment - thrombectomy

Andexanet: an antidote for Xa inhibitors

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

Anticoagulation after AF-stroke: how soon (or late?)

The rule TIA  1 day Small infarct  3 days Moderate infarct  6 days Large infarct  12 days

NOACs could be the answer? Ruff et al. Lancet 2013

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

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

NOAC vs. VKA: Intracranial haemorrhage Ruff et al. Lancet 2013

Take-home messages Rivaroxaban has similar effect across subgroups Switch VKAs to NOACs Interruption of NOACs for elective procedures Andexanet alpha is around the corner Recanalization techniques in anticoagulated acute-stroke patients Anticoagulation after ischemic stroke: how soon? Anticoagulation after intracerebral haemorrhage