Raffaele Ornello, MD

Broderick JP, Elm JJ, Janis LS, Zhao W, Moy CS, Dillon CR, Chimowitz MI, Sacco RL, Cramer SC, Wolf SL, et al. National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond. Stroke. 2020.

The National Institutes of Health StrokeNet is a wide collaborative network promoting trials in the field of stroke. The project was established in 2013, and, to date, it involves about 500 centers throughout the United States. Over the years, StrokeNet has given a substantial contribution to stroke research, not only favoring the completion of previously funded trials such as the POINT and SHINE trials, but also autonomously funding trials such as DEFUSE 3, ARCADIA, and Telerehab. StrokeNet also has educational goals and a special interest in homogenizing stroke imaging across sites.

The recent COVID-19 pandemic represented a challenge for stroke research, as it caused the forced suspension of all ongoing trials at the end of March and imposed rapid changes in protocols and operating procedures due to logistic barriers and safety concerns. In this context, StrokeNet showed a great capability of analyzing the new and unprecedented situation and providing rapid adaptations of the ongoing protocols. Those adaptations include a substantial use of telemedicine and remote solutions, the use of online surveys, an increasing use of innovative designs such as exemption from informed consent (EFIC), and reconsideration of processes such as timing of enrollment and outcome assessment. StrokeNet promptly responded to the COVID-19 pandemic, providing guidance to the principal investigators of ongoing trials, in which they were invited to adhere to safety recommendations and encouraged to use telemedicine, and modifying some aspects of data collection and patient follow-up due to the pandemic emergency.

Muhammad Rizwan Husain, MD
@RIZWANHUSAINMD

Robinson AA, Trankle CR, Eubanks G, Schumann C, Thompson P, Wallace RL, Gottiparthi S, Ruth B, Kramer CM, Salerno M, et al. Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi. JAMA Cardiol. 2020;5:685-692.

In this entry, I discuss the RED-VELVT observational study by Austin A. Robinson and colleagues about treating left ventricular (LV) thrombi with direct oral anticoagulants (DOACs) compared to warfarin and looking at rates of embolic events between the two treatment modalities.

Anecdotal data from the nineties, as well as the early 2000s, demonstrated a lower risk of systemic embolization with the use of warfarin or low molecular weight heparin (LMWH) compared to antiplatelets for LV thrombi. However, with the arrival of DOACs, anticoagulation therapy has been revolutionized due to ease of administration, no requirement for daily INR checks, no need for dietary alterations, and lower risk of bleeding events, to name a few. The benefit of DOACs for treatment of left atrial (LA) thrombus was noted in the X-TRA trial, and further benefit of DOACs was also seen in patients requiring anticoagulation for cardioversion (ENSURE-AF, EMANATE). Noting the benefits of DOACs in treating LA thrombus, many physicians have extrapolated the use of DOACs to treat LV thrombus. However, there has been no study to date to evaluate if DOACs fare better, worse, or the same compared to warfarin to reduce embolic events in patients with LV thrombi, and the authors in this study have attempted to answer this question.

Ravinder-Jeet Singh, MBBS, DM

Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, et al, for the DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. N Engl J Med. 2020; 382:1981-1993.

The treatment of patients with stroke having large vessel occlusion involves rapid, complete, and safe recanalization of the occluded vessel. Therefore, rapidity, efficacy and safety are three key attributes of any acute reperfusion therapy to improve functional outcomes. Mechanical retrieval of clot, endovascular thrombectomy (EVT), has all three attributes as shown in recent endovascular stroke trials and their meta-analysis.(1) Whether intravenous thrombolysis (IVT) has a synergistic effect in improving these attributes when combined with EVT remains unclear. Starting IVT before EVT adds some delay to the EVT, increases intracranial hemorrhage rates, and adds cost to the overall procedure. However, it could also lead to very early recanalization as shows in the EXTEND IA TNK trial(2) and improve quality of final reperfusion, possibly by clearing distal small emboli.(3) Functional relevance of these effects was not evident in the previous studies.(4) In DIRECT-MT, Yang et al. compared benefit and risk of administering intravenous alteplase before EVT.(5)

DIRECT-MT was a Chinese multicenter trial with PROBE (prospective, randomized, open-label trial with blinded outcome assessment) design similar to previous EVT trials. The patients (N=656) with ischemic stroke having large vessel occlusion and eligible to both IVT and EVT within 4.5 hours from symptom onset were enrolled. A total of 327 patients were randomized to undergo EVT (thrombectomy-alone group) and 329 to EVT plus IVT with alteplase (combination-therapy group).

Muhammad Rizwan Husain, MD
@RIZWANHUSAINMD

Douketis JD, Spyropoulos AC, Duncan J, Carrier M, Le Gal G, Tafur AJ, Vanassche T, Verhamme P, Shivakumar S, Gross PL, et al. Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med. 2019;179:1469-1478.

In this entry, I discuss a publication by Douketis and colleagues regarding the perioperative management of patients who have atrial fibrillation (AF) and are on a Direct oral anticoagulants (DOAC) and do not undergo a perioperative heparin bridge, who are then evaluated for rates of major bleeding and arterial thromboembolism.

DOACs have been in common use for AF since 2010, and there has been an increased use over the years due to its easy-to-administer dosing, no need for regular INR checks, nor any requirements for dietary adjustments. The concerns of intraoperative and post-operative bleeding with recent DOAC use, followed by the risk of an arterial embolic event like stroke while briefly off DOACs, has raised many concerns amongst physicians about when to stop and resume DOACs in patients scheduled for surgery. Furthermore, is there any benefit to bridge these patients with heparin during the perioperative period? The authors conduced the Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) study to help answer these questions, which involved a simple strategy to hold DOACs briefly depending on the bleeding risk of the elective procedure and to not bridge with heparin so as to keep a simple and standard interruption and resumption protocol for all physicians to follow. The primary outcome was to evaluate major bleeding and arterial thromboembolism (ischemic strokes or TIA and systemic embolism) from the time DOACs were stopped until 30 days post-operatively. Secondary outcomes included non-major bleeding, minor bleeding, death, MI, DVT or PE.