Letter by Hill et al Regarding Article, “A Cost-Utility Analysis of Mechanical Thrombectomy as an Adjunct to Intravenous Tissue-Type Plasminogen Activator for Acute Large-Vessel Ischemic Stroke”
To the Editor:
Therapy for acute ischemic stroke using endovascular approaches has seen widespread adoption in North America and Europe in the absence of randomized trials demonstrating better clinical outcomes. Surrogate outcomes, particularly target vessel recanalization, have been accepted by many in the neurological community and some regulatory authorities as adequate justification for clinical use. Remuneration has followed and is likely an important driver of endovascular therapy in the United States. A recent economic analysis by Kim et al1 serves to promote the endovascular approach by arguing the case on economic terms. However, we contest their assumptions and methodology as follows.
It is true that recanalization is a major predictor of a patient's clinical outcome. However, other factors may show particular importance, including the time to recanalization, the susceptibility of the tissue to infarction, and the degree of established infarction already present. Thus, assuming that recanalization is the only relevant factor is an oversimplification.
Recanalization rates defined by transcranial Doppler are limited by operator dependence and a lack of clear evidence of blinding. Convincing intravenous recombinant tissue-type plasminogen activator (alteplase) recanalization rate data are lacking and may be underestimated here.
The Interventional Management of Stroke (IMS) studies2,3 have demonstrated that recanalization of the target arterial occlusion (eg, middle cerebral artery stem) does not necessarily lead to reperfusion of the distal arterial bed. As a corollary, the occurrence of distal emboli into arterial territories not initially underperfused (eg, anterior carotid artery emboli) as a consequence of the endovascular procedure can result in significant additional infarction.4 Thus, recanalization can be non-nutritive, but the proportion of times this occurs is poorly quantified.
Poor outcomes are not governed entirely by the symptomatic intracerebral hemorrhage rate. Symptomatic intracerebral hemorrhage is a minor overall contributor to poor outcome; the major reason for poor outcome is the severity of the initial ischemic stroke. An economic model for a condition such as stroke should use longer-term outcomes, such as 90-day outcome rates including those who did poorly because of symptomatic intracerebral hemorrhage. Further, symptomatic intracerebral hemorrhage is associated with a high 30-day mortality, which may result in endovascular therapy appearing cheaper on average.
The safety of angiography used in the model was based on a large series of patients undergoing diagnostic angiography, not intervention, for which the risk is fundamentally higher. Further, patients who undergo diagnostic cerebral angiography do not require general anesthesia, whereas general anesthesia is a frequent approach in stroke patients treated endovascularly and is a factor that has been associated with poorer outcomes.
Patients treated in the MultiMERCI study were different from those treated in CLOTBUST and in the IMS studies,2,3 largely defined by time. Although a small subgroup of patients in MultiMERCI were treated with intravenous tissue-type plasminogen activator within 3 hours of stroke onset, most were treated endovascularly much later after stroke onset. Patients treated late tend to have self-selected better collateral flow, because those without good collateral flow already have had extensive infarction defined on baseline imaging, limiting their eligibility for any reperfusion strategy.
Thus, based on available data and knowledge, the conclusions reached by Kim et al are at best a promissory note to keep us hoping until there is sufficient strong evidence to change practice. It remains entirely possible that mechanical thrombectomy/thrombolysis as currently used is not cost-effective. Strong evidence for or against this practice will be forthcoming from the planned economic analysis of the IMS3 trial.5
Michael D. Hill, MD, MSc
Calgary Stroke Program
Department of Clinical Neurosciences
Hotchkiss Brain Institute
Calgary, Alberta, Canada
Pooja Khatri, MD
Thomas A. Tomsick, MD
Cincinnati Stroke Program
University of Cincinnati
Kit N. Simpson, DrPH
Medical University of South Carolina
Joseph P. Broderick, MD
Cincinnati Stroke Program
University of Cincinnati
M.D.H., P.K., T.T., and J.B.P. are members of the executive committee of the IMS3 trial, which is funded by NINDS (NIH-NINDS U01 NS052220 and U01 NS054630). The economic substudy is funded by the National Institute of Neurological Diseases and Stroke (NINDS U01 NS054630). The trial receives recombinant tissue-type plasminogen activator from Genentech and devices from Concentric, EKOS, and Johnson & Johnson. M.D.H. has been a consultant for Hoffmann-La Roche Canada, which holds the license for marketing of tPA in Canada.
Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).
- © 2011 American Heart Association, Inc.
- Kim AS,
- Nguyen-Huynh M,
- Johnston SC
The IMS Study Investigators. Combined intravenous and intra-arterial recanalization for acute ischemic stroke: The interventional management of stroke study. Stroke. 2004;35:904–911.
The IMS II Trial Investigators. The interventional management of stroke (IMS) II study. Stroke. 2007;38:2127–2135.
- King S,
- Khatri P,
- Carrozella J,
- Spilker J,
- Broderick J,
- Hill M,
- et al