[Industry-funded therapy studies: what is in the pipeline?]. / Industriegeförderte Therapiestudien : Was ist in der Pipeline?

Several acute stroke trials are underway or have been recently completed. Among the latter are the ICTUS trial and the IST-3 trial. Several other approaches are being tested for thrombolytic therapy among them modern imaging-based patient selection and new thrombolytic agents, such as desmoteplase and tenecteplase. Other strategies include neuroprotection and neurorestoration, biophysical approaches, such as near infrared laser therapy, hemodynamic augmentation and sphenopalatine ganglion stimulation. Mechanical thrombectomy is practiced in many centers although randomized trials are pending and the IMS-3 trial was stopped. This overview will cover the very recently completed and currently recruiting acute ischemic stroke trials.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. METHODS: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. RESULTS AND RECOMMENDATIONS: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

Clopidogrel in the management of cerebrovascular events.

The inhibition of platelet function has proved its effectiveness in the reduction of vascular events in many large trials for many different compounds such as ASA, ticlopinin, dipyridamole or clopidogrel. In this overview, the authors analyse the results of recent trials and present ongoing or future trials with clopidogrel. Clopidogrel has proved its superiority in prevention of vascular events as compared to ASA, being even higher in high-risk groups such as diabetic patients. For the post-interventional treatment of patients undergoing stent-protected dilatation of coronary arteries, the combination of ASA and clopidogrel has become a standard procedure. There is also evidence that the combination of ASA and Clopidogrel is better than ASA alone in long-term treatment up to at least 9 months. The long-term combination therapy seems to be very promising and is currently analysed in three large trials in over 30,000 patients with a large number of stroke patients. These trials will also answer the question, whether the combination therapy is safe in long-term secondary stroke prevention. However, there is still a widespread reluctance in doctors to prescribe Clopidogrel for its costs. Cost-effectiveness studies predict up to tenfold higher cost in the prevention of vascular events when compared to ASA, in times of shrinking health budgets a topic of interest.

Thrombolytic therapy for ischemic stroke--a review. Part II--Intra-arterial thrombolysis, vertebrobasilar stroke, phase IV trials, and stroke imaging.

OBJECTIVE: Intra-arterial thrombolytic therapy for carotid and vertebrobasilar stroke may result in a more rapid clot lysis and higher recanalization rates than can be achieved with intravenous thrombolysis and thus may warrant the more invasive and time-consuming therapeutic approach. We present an overview of all hitherto completed trials of intra-arterial thrombolytic therapy for carotid and vertebrobasilar artery stroke including recommendations for therapy and a meta-analysis. Furthermore, new imaging techniques such as diffusion- and perfusion-weighted magnetic resonance imaging and their impact on patient selection are discussed. Finally, phase IV trials of thrombolysis in general and cost efficacy analyses are presented. DATA SOURCES: We performed an extensive literature search not only to identify the larger and well-known randomized trials but also to identify smaller pilot studies and case series. Trials included in this review, among others, are the PROACT I and PROACT II studies and the Cochrane Library report. CONCLUSION: Intra-arterial thrombolytic therapy of acute M1 and M2 occlusions with 9 mg/2 hrs pro-urokinase significantly improves outcome if administered within 6 hrs after stroke onset. Seven patients need to be treated to prevent one patient from death or dependence. Vertebrobasilar occlusion has a grim prognosis and intra-arterial thrombolytic therapy to date is the only life-saving therapy that has demonstrated benefit with regard to mortality and outcome, albeit not in a randomized trial. New magnetic resonance imaging techniques may facilitate and improve the selection of patients for thrombolytic therapy. Presently, thrombolytic therapy is still underutilized because of problems with clinical and time criteria, and lack of public and professional education to regard stroke as a treatable emergency. If applied more widely, thrombolytic therapy may result in profound cost savings in health care and reduction of long-term disability of stroke patients.