Practicing Evidence-Based Stroke Medicine

The practice of evidence-based medicine depends on several steps: a basic science derived understanding of disease pathophysiology, epidemiological research, and the results of well-conducted and appropriately analyzed randomized clinical trials (RCTs). The approval of new therapies by regulatory agencies is also based largely on RCT determination of the safety and therapeutic efficacy of drugs and devices. Once a new therapy is approved for use in clinical practice, clinicians typically begin to use it in a manner which mirrors the clinical trial design, for example, in the population for who risk and benefit have been established. It must be acknowledged that in the United States and in other countries, clinicians have leeway in their therapeutic decision making and it is not uncommon for therapies to be used for situations not tested in the RCTs that led to approval, the so-called off-label use. The off-label use of stroke-related therapies is relatively common, and we will consider the appropriateness of doing this in 3 common clinical scenarios.The relatively recent demonstration of the efficacy of thrombectomy within 6 hours of stroke onset in 6 well-conducted RCTs provides convincing evidence that this treatment is highly effective in improving functional outcome.1,2 These RCTs carefully selected patients with small-to-moderate ischemic cores, primarily by assessing the pretreatment Alberta Stroke Program Early CT Score (ASPECTS) on a noncontrast head CT, but computerized tomography perfusion (CTP) and diffusion-weighted magnetic resonance imaging were also acquired in some patients. In these trials, the median baseline ASPECTS score was 9, indicating a very small ischemic core and in 3 of the trials a baseline score of ≤5 was an exclusion. Even in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a trial which did not specify an ASPECTS exclusion criterion, the …