Thread by @StrokeBern

1/ 76 yo woman suffers an ischemic stroke in the left media territory, initial NIHSS 5. Treated with IVT. NIHSS at 24hs 3 points, new diagnosis of #AFib on the #Stroke unit monitor/ECG… 24h MRI shown belowê When would you start anticoagulation?

2/ When would you start DOAC therapy in this woman?
Let's dive into the NEWEST evidence to find the optimal timing! #StrokeCare #AFib @ELAN_Trial @FishingNeurons #ESOC2023

3/ Non-valvular atrial fibrillation accounts for about 25% of ischemic strokes. Early recurrent strokes are common, but starting oral anticoagulation too soon may increase the risk of harmful intracranial bleeding. We need a balance… or do we???

4/ Historical data relied on heparins, or vitamin K antagonists (VKAs). However, direct oral anticoagulants (DOACs) have shown comparable efficacy with half the risk of intracranial hemorrhage in 2nd prevention!

5/ Various guidelines recommend different timings, but they lack precision and consistency. The "1-3-6-12 days rule" and AHA/ASA guidelines suggest starting oral anticoagulation within 4-14 days, whereas UK guidelines recommend deferral for 14 days in disabling stroke. 🗒️📋

6/ The catch? None of the DOAC trials included patients with recent ischemic strokes and stroke severity does not adequately reflect size and location of infarction and neglects other predictors of symptomatic hemorrhage like hemorrhagic transformation.
sciencedirect.com/science/articl…

7/ Prospective observational studies and small randomized trials have investigated early DOAC initiation. The risk for ischemic events seemed to outweigh the hemorrhagic complications! 📚🔬 @DavidSeiffge sciencedirect.com/science/articl…

8/ In this issue of the @NEJM the @ELAN_Trial by @FishingNeurons made @StrokeBern @CTUBern is published! 💪🔬 Protocol here:
journals.sagepub.com/doi/full/10.11…

9/ It compared whether a more early initiation of DOAC therapy as compared to late guideline-based initiation in AF-related ischemic stroke was safe and effective. Importantly, severity of stroke WAS NOT defined by NIHSS, but by imaging assessment of infarct size!

10/ This international, multicentre, randomised (1:1) controlled, PROBE trial randomized 2013 patients at 103 (!) sites in 15 countries worldwide.
elan-trial.ch/participating-…

11/ Early treatment was defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after 12–14d post major stroke

12/ The primary outcome was the composite of sICH, major extracranial bleeding, recurrent ischemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomization. The trial was powered assuming a risk difference of 0.5% favouring the early arm.

13/ The population was very representative of our daily stroke unit #AFib patients (median age 77, CHADS-VASC 5, NIHSS at randomization 3, 40% IVT, 22% MT.
Almost 50% woman participation in this trial! Well done @FishingNeurons!

14/ The co-primary-outcome at 30 days occurred in 29 (2.9%) in the early-treatment group and 41 (4.1%) in the later-treatment group (risk difference, −1.18%; 95% CI, −2.84 to 0.47) by 30 days.

15/ Recurrent ischemic stroke by 30 days occurred in 14 (1.4%) in the early-treatment group and 25 (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07). sICH occurred in 2 participants (0.2%) in both groups by 30 days.

16/ Secondary outcomes were similar across groups without safety concerns with early treatment.

17/ There were some hypothesis-generating subgroup differences, that warrant further exploration, e.g. potential benefit of early treatment bigger with higher NIHSS and larger size, as well as females?

18/ With this trial, we are quite sure, that anticoagulation can safely be started earlier than currently recommended. The chances of suffering a recurrent ischaemic stroke with earlier treatment are likely to be lower, without any increased risk of 🩸if imaging selection is used

19/ See the example: in the 1st panel there is a 98% probability that early DOAC will increase the risk of the primary composite outcome by not more than 0.5% (green arrows).

20/ Some things to consider:
- median NIHSS 3, but subgroup analysis of severe stroke reassuring
- mostly European population
- PH1 or PH2 at baseline not included
➡️ More data and meta-analysis of further #RCTs on this topic needed! @OPTIMAS_UCL @BoNorrving

21/ Witnessing the incredible amount of work that has gone into this trial over the last years and contributing a very tiny bit by including patients reminds me of #BottleClaus

22/ It gives you the chills and will motivate many of us to continue to participate, enroll and design future trials. @FishingNeurons @StrokeBern @DavidSeiffge @tecno @Switch

23/ Thanks so much to the public funders and supporters of the @ELAN_Trial @snf_ch @HerzstiftungCH @inselgruppe @unibern

Thoughts? Comments?

@adnan_mujanovic @MicieliA_MD @Ash_Shoamanesh @StrokeAHA_ASA @EANeurology @Diana_A_Sousa @AshuPJadhav @AlexanderPBenz @Morin91126916 @ECSandset @ChaturvediNeuro @CheesemakerMD @a_charidimou @DavidSeiffge @TDobrocky @dgn_ev @hirnstiftung @ESOstroke @MASStroke @escardio @mbgoeldlin

@American_Heart @IntJStroke @JACCJournals @JAMANeuro @jeyaraj_pandian @RaberLorenz @TheLancetNeuro @NguyenThanhMD @WorldStrokeOrg @NeurologyToday @ShadiYaghi2 @StrokeCliTrials @TheStrokeAssoc @Stroke_School

Pulication here:
nejm.org/?query=feature…