Safety and efficacy of ultrasound-enhanced thrombolysis

A comprehensive review and meta-analysis of randomized and nonrandomized studies

Georgios Tsivgoulis, Jürgen Eggers, Marc Ribo, Fabienne Perren, Maher Saqqur, Marta Rubiera, Theodoros N. Sergentanis, Konstantinos Vadikolias, Vincent Larrue, Carlos A. Molina, Andrei Alexandrov

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Background and Purpose-Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). SUBJECTS AND Methods-Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cérébral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (μS), tPA+TCCD±μS, and tPA+low-frequency ultrasound. Results-A total of 6 randomized (n=224) and 3 nonrandomized (n=192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA+TCD, 3.8% (95% CI, 0%-11.2%); tPA+TCCD, 11.1% (95% CI, 0%-28.9%); tPA+low-frequency ultrasound, 35.7% (95% CI, 16.2%-61.4%); and tPA alone, 2.9% (95% CI, 0%-8.4%). Complete recanalization rates were higher in patients receiving combination of TCD with tPA 37.2% (95% CI, 26.5%-47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%-24.9%). In 8 trials of high-frequency (TCD/TCCD) ultrasound-enhanced thrombolysis, tPA+TCD/ TCCD±μS was associated with a higher likelihood of complete recanalization (pooled OR, 2.99; 95% CI, 1.70-5.25; P=0.0001) when compared to tPA alone. High-frequency ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled OR, 1.26; 95% CI, 0.44-3.60; P=0.67). Conclusions-The present safety and signal-of-efficacy data of high-frequency ultrasound-enhanced thrombolysis should be taken into account in the design of future randomized controlled trials.

Original languageEnglish (US)
Pages (from-to)280-287
Number of pages8
JournalStroke
Volume41
Issue number2
DOIs
StatePublished - Feb 1 2010

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Tissue Plasminogen Activator
Meta-Analysis
Safety
Cerebral Hemorrhage
Color
Standard of Care
Reperfusion
Publications
Ischemia
Randomized Controlled Trials
Stroke

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Safety and efficacy of ultrasound-enhanced thrombolysis : A comprehensive review and meta-analysis of randomized and nonrandomized studies. / Tsivgoulis, Georgios; Eggers, Jürgen; Ribo, Marc; Perren, Fabienne; Saqqur, Maher; Rubiera, Marta; Sergentanis, Theodoros N.; Vadikolias, Konstantinos; Larrue, Vincent; Molina, Carlos A.; Alexandrov, Andrei.

In: Stroke, Vol. 41, No. 2, 01.02.2010, p. 280-287.

Research output: Contribution to journalArticle

Tsivgoulis, G, Eggers, J, Ribo, M, Perren, F, Saqqur, M, Rubiera, M, Sergentanis, TN, Vadikolias, K, Larrue, V, Molina, CA & Alexandrov, A 2010, 'Safety and efficacy of ultrasound-enhanced thrombolysis: A comprehensive review and meta-analysis of randomized and nonrandomized studies', Stroke, vol. 41, no. 2, pp. 280-287. https://doi.org/10.1161/STROKEAHA.109.563304
Tsivgoulis, Georgios ; Eggers, Jürgen ; Ribo, Marc ; Perren, Fabienne ; Saqqur, Maher ; Rubiera, Marta ; Sergentanis, Theodoros N. ; Vadikolias, Konstantinos ; Larrue, Vincent ; Molina, Carlos A. ; Alexandrov, Andrei. / Safety and efficacy of ultrasound-enhanced thrombolysis : A comprehensive review and meta-analysis of randomized and nonrandomized studies. In: Stroke. 2010 ; Vol. 41, No. 2. pp. 280-287.
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T1 - Safety and efficacy of ultrasound-enhanced thrombolysis

T2 - A comprehensive review and meta-analysis of randomized and nonrandomized studies

AU - Tsivgoulis, Georgios

AU - Eggers, Jürgen

AU - Ribo, Marc

AU - Perren, Fabienne

AU - Saqqur, Maher

AU - Rubiera, Marta

AU - Sergentanis, Theodoros N.

AU - Vadikolias, Konstantinos

AU - Larrue, Vincent

AU - Molina, Carlos A.

AU - Alexandrov, Andrei

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Background and Purpose-Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). SUBJECTS AND Methods-Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cérébral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (μS), tPA+TCCD±μS, and tPA+low-frequency ultrasound. Results-A total of 6 randomized (n=224) and 3 nonrandomized (n=192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA+TCD, 3.8% (95% CI, 0%-11.2%); tPA+TCCD, 11.1% (95% CI, 0%-28.9%); tPA+low-frequency ultrasound, 35.7% (95% CI, 16.2%-61.4%); and tPA alone, 2.9% (95% CI, 0%-8.4%). Complete recanalization rates were higher in patients receiving combination of TCD with tPA 37.2% (95% CI, 26.5%-47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%-24.9%). In 8 trials of high-frequency (TCD/TCCD) ultrasound-enhanced thrombolysis, tPA+TCD/ TCCD±μS was associated with a higher likelihood of complete recanalization (pooled OR, 2.99; 95% CI, 1.70-5.25; P=0.0001) when compared to tPA alone. High-frequency ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled OR, 1.26; 95% CI, 0.44-3.60; P=0.67). Conclusions-The present safety and signal-of-efficacy data of high-frequency ultrasound-enhanced thrombolysis should be taken into account in the design of future randomized controlled trials.

AB - Background and Purpose-Ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3 different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care (intravenous tPA). SUBJECTS AND Methods-Through Medline, Embase, and Cochrane database search, we identified and abstracted all studies of ultrasound-enhanced thrombolysis in acute cérébral ischemia. Principal investigators were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage (sICH) and recanalization rates were compared between tPA, tPA+TCD±microspheres (μS), tPA+TCCD±μS, and tPA+low-frequency ultrasound. Results-A total of 6 randomized (n=224) and 3 nonrandomized (n=192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA+TCD, 3.8% (95% CI, 0%-11.2%); tPA+TCCD, 11.1% (95% CI, 0%-28.9%); tPA+low-frequency ultrasound, 35.7% (95% CI, 16.2%-61.4%); and tPA alone, 2.9% (95% CI, 0%-8.4%). Complete recanalization rates were higher in patients receiving combination of TCD with tPA 37.2% (95% CI, 26.5%-47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%-24.9%). In 8 trials of high-frequency (TCD/TCCD) ultrasound-enhanced thrombolysis, tPA+TCD/ TCCD±μS was associated with a higher likelihood of complete recanalization (pooled OR, 2.99; 95% CI, 1.70-5.25; P=0.0001) when compared to tPA alone. High-frequency ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled OR, 1.26; 95% CI, 0.44-3.60; P=0.67). Conclusions-The present safety and signal-of-efficacy data of high-frequency ultrasound-enhanced thrombolysis should be taken into account in the design of future randomized controlled trials.

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