Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke

A comprehensive benefit-risk analysis of clinical trials

Georgios Tsivgoulis, John Alleman, Aristeidis H. Katsanos, Andrew D. Barreto, Martin Kohrmann, Peter D. Schellinger, Carlos A. Molina, Andrei Alexandrov

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Background: Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit-risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT). Methods: A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0-1) or functional independence (BRR2, mRS score: 0-2) at 3 months divided by the percentage of patients who died during the same period. Results: A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31-0.65; BRR2 range, 0.52-1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R2 value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies. Conclusion: Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.

Original languageEnglish (US)
Pages (from-to)789-797
Number of pages9
JournalBrain and Behavior
Volume4
Issue number6
DOIs
StatePublished - Nov 1 2014

Fingerprint

Reperfusion
Stroke
Clinical Trials
Therapeutics
Odds Ratio
Thrombectomy
Investigational Therapies
Clinical Studies

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke : A comprehensive benefit-risk analysis of clinical trials. / Tsivgoulis, Georgios; Alleman, John; Katsanos, Aristeidis H.; Barreto, Andrew D.; Kohrmann, Martin; Schellinger, Peter D.; Molina, Carlos A.; Alexandrov, Andrei.

In: Brain and Behavior, Vol. 4, No. 6, 01.11.2014, p. 789-797.

Research output: Contribution to journalReview article

Tsivgoulis, Georgios ; Alleman, John ; Katsanos, Aristeidis H. ; Barreto, Andrew D. ; Kohrmann, Martin ; Schellinger, Peter D. ; Molina, Carlos A. ; Alexandrov, Andrei. / Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke : A comprehensive benefit-risk analysis of clinical trials. In: Brain and Behavior. 2014 ; Vol. 4, No. 6. pp. 789-797.
@article{ec63a37b420c490f9da084f14c3f4830,
title = "Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: A comprehensive benefit-risk analysis of clinical trials",
abstract = "Background: Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit-risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT). Methods: A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0-1) or functional independence (BRR2, mRS score: 0-2) at 3 months divided by the percentage of patients who died during the same period. Results: A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31-0.65; BRR2 range, 0.52-1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R2 value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies. Conclusion: Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.",
author = "Georgios Tsivgoulis and John Alleman and Katsanos, {Aristeidis H.} and Barreto, {Andrew D.} and Martin Kohrmann and Schellinger, {Peter D.} and Molina, {Carlos A.} and Andrei Alexandrov",
year = "2014",
month = "11",
day = "1",
doi = "10.1002/brb3.279",
language = "English (US)",
volume = "4",
pages = "789--797",
journal = "Brain and Behavior",
issn = "2157-9032",
publisher = "John Wiley and Sons Inc.",
number = "6",

}

TY - JOUR

T1 - Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke

T2 - A comprehensive benefit-risk analysis of clinical trials

AU - Tsivgoulis, Georgios

AU - Alleman, John

AU - Katsanos, Aristeidis H.

AU - Barreto, Andrew D.

AU - Kohrmann, Martin

AU - Schellinger, Peter D.

AU - Molina, Carlos A.

AU - Alexandrov, Andrei

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Background: Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit-risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT). Methods: A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0-1) or functional independence (BRR2, mRS score: 0-2) at 3 months divided by the percentage of patients who died during the same period. Results: A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31-0.65; BRR2 range, 0.52-1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R2 value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies. Conclusion: Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.

AB - Background: Numerous acute reperfusion therapies (RPT) are currently investigated as potential new therapeutic targets in acute ischemic stroke (AIS). We conducted a comprehensive benefit-risk analysis of available clinical studies assessing different acute RPT, and investigated the utility of each intervention in comparison to standard intravenous thrombolysis (IVT) and in relation to the onset-to-treatment time (OTT). Methods: A comprehensive literature search was conducted to identify all available published, peer-reviewed clinical studies that evaluated the efficacy of different RPT in AIS. Benefit-to-risk ratio (BRR), adjusted for baseline stroke severity, was estimated as the percentage of patients achieving favorable functional outcome (BRR1, mRS score: 0-1) or functional independence (BRR2, mRS score: 0-2) at 3 months divided by the percentage of patients who died during the same period. Results: A total of 18 randomized (n = 13) and nonrandomized (n = 5) clinical studies fulfilled our inclusion criteria. IV therapy with tenecteplase (TNK) was found to have the highest BRRs (BRR1 = 5.76 and BRR2 = 6.82 for low-dose TNK; BRR1 = 5.80 and BRR2 = 6.87 for high-dose TNK), followed by sonothrombolysis (BRR1 = 2.75 and BRR2 = 3.38), while endovascular thrombectomy with MERCI retriever was found to have the lowest BRRs (BRR1 range, 0.31-0.65; BRR2 range, 0.52-1.18). A second degree negative polynomial correlation was detected between favorable functional outcome and OTT (R2 value: 0.6419; P < 0.00001) indicating the time dependency of clinical efficacy of all reperfusion therapies. Conclusion: Intravenous thrombolysis (IVT) with TNK and sonothrombolysis have the higher BRR among investigational reperfusion therapies. The combination of sonothrombolysis with IV administration of TNK appears a potentially promising therapeutic option deserving further investigation.

UR - http://www.scopus.com/inward/record.url?scp=84907959562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907959562&partnerID=8YFLogxK

U2 - 10.1002/brb3.279

DO - 10.1002/brb3.279

M3 - Review article

VL - 4

SP - 789

EP - 797

JO - Brain and Behavior

JF - Brain and Behavior

SN - 2157-9032

IS - 6

ER -