J L Saver1. 1. Stroke Center and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA. jsaver@ucla.edu
Abstract
BACKGROUND: The first generation of clinical reperfusion treatment, intravenous (IV) fibrinolysis with tissue plasminogen activator (tPA), was a transformative breakthrough in stroke care, but is far from ideal. OBJECTIVES: TO survey emerging strategies to increase the efficacy and safety of cerebral reperfusion therapy. METHODS: Narrative review. RESULTS AND CONCLUSIONS: Innovative IV pharmacologic reperfusion strategies include: extending IV tPA use to patients with mild deficits; developing novel fibrinolytic agents (tenecteplase, desmetolplase, plasmin); using ultrasound to enhance enzymatic fibrinolysis; combination clot lysis therapies (fibrinolytics with GPIIb/IIIa agents or direct thrombin inhibitors); co-administration of MMP-9 inhibitors to deter haemorrhagic transformation; and prehospital neuroprotection to support threatened tissues until reperfusion. Endovascular recanalisation strategies are rapidly evolving, and include intra-arterial fibrinolysis, mechanical clot retrieval, suction thrombectomy, and primary stenting. Combined approaches appear especially promising, using IV fibrinolysis to rapidly initiate reperfusion, mechanical endovascular treatment to debulk large, proximal thrombi, and intra-arterial (IA) fibrinolysis to clear residual distal thrombus elements and emboli.
BACKGROUND: The first generation of clinical reperfusion treatment, intravenous (IV) fibrinolysis with tissue plasminogen activator (tPA), was a transformative breakthrough in stroke care, but is far from ideal. OBJECTIVES: TO survey emerging strategies to increase the efficacy and safety of cerebral reperfusion therapy. METHODS: Narrative review. RESULTS AND CONCLUSIONS: Innovative IV pharmacologic reperfusion strategies include: extending IV tPA use to patients with mild deficits; developing novel fibrinolytic agents (tenecteplase, desmetolplase, plasmin); using ultrasound to enhance enzymatic fibrinolysis; combination clot lysis therapies (fibrinolytics with GPIIb/IIIa agents or direct thrombin inhibitors); co-administration of MMP-9 inhibitors to deter haemorrhagic transformation; and prehospital neuroprotection to support threatened tissues until reperfusion. Endovascular recanalisation strategies are rapidly evolving, and include intra-arterial fibrinolysis, mechanical clot retrieval, suction thrombectomy, and primary stenting. Combined approaches appear especially promising, using IV fibrinolysis to rapidly initiate reperfusion, mechanical endovascular treatment to debulk large, proximal thrombi, and intra-arterial (IA) fibrinolysis to clear residual distal thrombus elements and emboli.
Authors: Jeffrey L Saver; Sidney Starkman; Marc Eckstein; Samuel Stratton; Frank Pratt; Scott Hamilton; Robin Conwit; David S Liebeskind; Gene Sung; Nerses Sanossian Journal: Int J Stroke Date: 2014-01-13 Impact factor: 5.266
Authors: Devin William McBride; Guangyong Wu; Derek Nowrangi; Jerry J Flores; Liang Hui; Paul R Krafft; John H Zhang Journal: Transl Stroke Res Date: 2018-01-21 Impact factor: 6.829
Authors: Madhuvanthi A Kandadai; Jason M Meunier; Kimberley Hart; Christy K Holland; George J Shaw Journal: Transl Stroke Res Date: 2014-11-20 Impact factor: 6.829
Authors: Jeffrey L Saver; Tudor G Jovin; Wade S Smith; Gregory W Albers; Jean-Claude Baron; Johannes Boltze; Joseph P Broderick; Lisa A Davis; Andrew M Demchuk; Salvatore DeSena; Jens Fiehler; Philip B Gorelick; Werner Hacke; Bill Holt; Reza Jahan; Hui Jing; Pooja Khatri; Chelsea S Kidwell; Kennedy R Lees; Michael H Lev; David S Liebeskind; Marie Luby; Patrick Lyden; J Thomas Megerian; J Mocco; Keith W Muir; Howard A Rowley; Richard M Ruedy; Sean I Savitz; Vitas J Sipelis; Samuel K Shimp; Lawrence R Wechsler; Max Wintermark; Ona Wu; Dileep R Yavagal; Albert J Yoo Journal: Stroke Date: 2013-11-05 Impact factor: 7.914