Wednesday, October 22, 2014: 10:15 AM

Ankur Pandya, PhD, Ashley A. Eggman, MS, Hooman Kamel, MD, Ajay Gupta, MD, Bruce R. Schackman, PhD and Pina C. Sanelli, MD, MPH, Weill Cornell Medical College, New York, NY

Purpose: Thrombolytic treatment (tissue-type plasminogen activator [tPA]) is only recommended for acute ischemic stroke patients with stroke onset time <4.5 hours due to higher bleeding risks with onset time >4.5 hours. tPA is not recommended when stroke onset time is unknown (14-28% of ischemic strokes). Magnetic resonance imaging (MRI) of the brain can be used to estimate stroke onset time with considerable accuracy. We projected health benefits, risks, and costs of image-based treatment decisions versus the current recommendation (no treatment) for acute stroke patients with unknown stroke onset time.

Methods: We developed a micro-simulation model that assigned patients a true stroke onset time from a beta distribution (average value 6.5 hours with uniform probability between 2.5-10.5 hours). Brain MRI used to estimate stroke onset time had estimated sensitivity and specificity of 0.62 and 0.78 respectively from the literature, cost $488, and delayed treatment by 30 minutes. True stroke onset time affected the impact of tPA on the probability of a favorable acute stroke outcome (modified Rankin score of 0-1 [mRS0-1]; odds ratio range 1.0-2.6 depending on true onset time) and the risk of major bleeding events (substantial intracerebral hemorhrage [sICH]; odds ratio range 3.5-8.5). Cost, utility, and disease progression parameters were estimated from published sources and depended on treatment status (tPA cost $16,740), mRS (utility values range 0.2-0.8), and sICH (54% fatal) outcomes. Discounted lifetime costs and health benefits (quality-adjusted life years [QALYs]) were projected for each strategy. In a sensitivity analysis, true stroke time was assumed to be left-skewed (average 4.8 hours with skewed beta distribution).

Results: With no treatment, 45.1% and 1.0% patients with unknown stroke time experienced mRS0-1 and sICH outcomes, respectively, with 5.125 lifetime QALYs and $86,949 lifetime costs; the image-based strategy resulted in 46.4% mRS0-1, 3.0% sICH, 5.150 QALYs, and $92,356 costs. The incremental cost-effectiveness ratio (ICER) for image-based treatment versus no treatment was $220,000/QALY. The ICER using a left-skewed beta distribution was $91,000/QALY. Results were sensitive to MRI sensitivity and specificity (Figure).

Conclusions: The cost-effectiveness of image-based treatment decisions versus the current recommendation of no tPA treatment for acute stroke patients with unknown onset time is sensitive to assumptions about true stroke onset time. Cost-effective image-based treatment (<$100,000/QALY) for these patients could be achieved with improved MRI diagnostic performance.