Meta-Analysis of Studies Supports Ultrasound-Enhanced Thrombolysis

In Stroke, Georgios Tsivgoulis, MD, et al published a review of the safety and efficacy data for ultrasound-enhanced thrombolysis (2010;41:280-287).

According to the investigators, ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, three 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. In this study, the investigators performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care, intravenous tPA.

From their findings, the investigators concluded that 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.

As detailed in Stroke, the investigators used Medline, Embase, and Cochrane database searches to identify and abstract all studies of ultrasound-enhanced thrombolysis in acute cerebral ischemia. Principal investigators of those studies were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage and recanalization rates were compared between tPA, tPA + TCD ± microspheres (µS), tPA + TCCD ± µS, and tPA + low-frequency ultrasound.

The investigators reported that a total of six randomized (n = 224) and three nonrandomized (n = 192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA + TCD, 3.8% (95% confidence interval [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 a 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 eight trials of high-frequency (TCD/TCCD), ultrasound-enhanced thrombolysis, tPA + TCD/TCCD ± µS was associated with a higher likelihood of complete recanalization (pooled odds ratio, 2.99; 95% CI, 1.7–5.25; P = .0001) when compared to tPA alone. High-frequency, ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled odds ratio, 1.26; 95% CI, 0.44–3.6; P = .67).