Intravenous Thrombolysis for Acute Ischemic Stroke

Abstract

OBJECTIVEThis article reviews the history of IV thrombolysis, its current indications and implementation, the duality of the “time is brain” versus “tissue clock” approaches, the impact of endovascular thrombectomy on IV thrombolysis, the emergence of tenecteplase, and future research directions.LATEST DEVELOPMENTSThe growing use of factor Xa inhibitors has increasingly caused patients with stroke to be excluded from treatment with IV thrombolysis. Important geographic, socioeconomic, sex, race, and ethnic disparities have been identified in the implementation of IV thrombolysis and need to be overcome. IV thrombolysis substantially improves outcomes when provided within the first golden hour after stroke onset in patients treated in mobile stroke units, supporting the “time is brain” concept and encouraging the possible value of more widespread implementation of the mobile stroke unit approach. At the same time, other studies have shown that IV thrombolysis can be successful in patients whose “tissue clock” is still ticking up to 9 hours after stroke onset or in patients who awaken with their stroke, as demonstrated by favorable imaging profiles. These considerations, along with the emergence of endovascular thrombectomy, have fostered examination of our care systems, including the “drip and ship” versus direct to comprehensive or endovascular thrombectomy stroke center approaches, as well as the possibility of skipping IV thrombolysis in certain patients treated with endovascular thrombectomy. Data suggesting that tenecteplase is at least noninferior to alteplase, as well as its more convenient dosing, has led to its increased use. Ongoing studies are evaluating newer thrombolytics and adding antithrombotic therapy to IV thrombolysis.ESSENTIAL POINTSIV thrombolysis remains the most common acute stroke treatment. Advances in acting faster to treat stroke have increased its efficacy, and advances in imaging have expanded its use. However, implementing these advances and overcoming disparities in IV thrombolysis use remain major challenges.

A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase

“…After reviewing the current literature, there appears to be somewhat conflicting data regarding the safety and efficacy of tenecteplase compared to alteplase. A recent meta-analysis and multiple multicenter randomized trials reported that tenecteplase in AIS was non-inferior to alteplase in AIS with comparable safety and effectiveness [ 10 , 11 , 14 ]. Similarly, a systematic review of multiple non-randomized studies showed a comparable rate of ICH, better recanalization, and earlier neurologic improvement with tenecteplase compared to alteplase [ 33 ].…”

“…A literature review demonstrates comparable safety between tenecteplase and alteplase [ 10 - 14 ]. Tenecteplase administration offers several advantages over alteplase.…”

Medical Management of Acute Cerebral Ischemia

“…These modified versions of tPA have slightly different properties, such as their ability to bind to fibrin and their half-life. 9 Alteplase was the first modified version of tPA to be studied.…”

“…While the importance of thrombolysis cannot be overstated, it is important to recognize that almost 90% of the patients that present to the hospital with stroke symptoms are not candidates for IV thrombolysis. 9 Early treatment for these patients starts with the initial evaluation and correction of blood glucose, blood pressure, and other measures outlined above.…”

Intravenous Thrombolysis in Acute Ischemic Stroke

“…Alteplase (recombinant tissue plasminogen activator or rtPA) is the recombinant form of the endogenous tissue plasminogen activator (tPA). Following the successful NINDS trial in 1995 showing improved outcomes in stroke patients, rtPA was approved by the Food and Drug Administration (FDA) for use within 3 h of onset of ischemic stroke symptoms [10,12]. It is administered at a total dose of 0.9 mg/ kg with a maximum dose of 90 mg. A dose of 0.6 mg/kg with a maximum of 60 mg is however studied and approved for use in Japan.…”