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Review
. 2014;4(6):789-97.
doi: 10.1002/brb3.279. Epub 2014 Sep 11.

Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit-risk analysis of clinical trials

Georgios Tsivgoulis  1 , John Alleman  2 , Aristeidis H Katsanos  3 , Andrew D Barreto  4 , Martin Kohrmann  5 , Peter D Schellinger  6 , Carlos A Molina  7 , Andrei V Alexandrov  8
Affiliations
Review

Comparative efficacy of different acute reperfusion therapies for acute ischemic stroke: a comprehensive benefit-risk analysis of clinical trials

Georgios Tsivgoulis et al. Brain Behav. 2014.

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 (R (2) 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.

Keywords: Acute stroke; analysis; benefit-to-risk ratio; reperfusion therapies.

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Figures

Figure 1
Figure 1
Histogram of baseline NIHSS values across included studies. NIHSS, National Institute of Health Stroke Scale.
Figure 2
Figure 2
Plot of 90-day modified Rankin Scale scores versus time to treatment.
Figure 3
Figure 3
Benefit-to-risk ratio versus onset-to-treatment time. IV, intravenous; TCD, transcranial; SOC, standard of care.
See this image and copyright information in PMC

References

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