TPA for Acute Ischemic Stroke - Oren Zarif - TPA Stroke

The current evidence supporting the use of tPA to treat acute ischemic stroke is mixed. The American College of Emergency Physicians (ACEP) and the Academy of Neurology appointed a joint development panel to draft clinical guidelines. The results were presented at the AAN annual meeting. A second panel of independent experts was appointed to evaluate the clinical effectiveness of tPA in the treatment of acute ischemic stroke. Its findings are based on extensive research.

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Although tPA is the only treatment currently approved by the FDA for acute ischemic stroke, it is associated with significant risks, including increased rates of hemorrhage, reperfusion injury, and mortality. Additionally, delayed tPA administration may lead to an increased risk of mortality and reperfusion injury. Moreover, tPA can activate matrix metalloproteases, which can disrupt the blood-brain barrier (BBB) further.

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One trial, the IST-3, aimed to evaluate the effects of tPA in patients with ischemic stroke within six hours after symptom onset. However, the vast majority of IST-3 patients had contraindications to tPA and ECASS-3. Because the study was based on a different cohort of patients than those who were eligible for tPA treatment in this guideline, the results from IST-3 were not applicable to the current guidelines. Because of these limitations, future studies should focus on advancing neuroimaging and improving the ability of physicians to identify patients who are at high risk for tPA stroke.

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The initial studies on tPA were conducted in the early 1980s. However, they were performed on animals and a small number of stroke patients. A major breakthrough in biotechnology made it possible for scientists to clone genes and directly express protein in cell cultures. Genentech was able to successfully produce recombinant tPA in sufficient quantities for commercial use. The National Heart, Lung, and Blood Institute (NHLBI) supported the first multicenter randomized clinical trial in 1984.

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Another clinical trial examined the effect of tPA on ischemic brain tissue. Researchers found that PDTC significantly reduced the incidence of HT and ICH in patients with ischemic stroke. It also inhibited the phosphorylation of the nuclear factor NF-kB, which is thought to be prosurvival. Interestingly, PDTC was administered at the same time as tPA to rats with acute ischemic stroke.

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tPA was approved for use in the United States by the Food and Drug Administration (FDA) in 1996. The study was funded by the NINDS and the National Institutes of Health (NIH). The study also found that tPA improved the outcome without increasing mortality. In the meantime, the FDA continues to evaluate tPA for other uses. The results of that study are crucial for the development of stroke therapies. Once approved, tPA will continue to prove its effectiveness.

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In a Class III trial, a network of German hospitals found that tPA stroke patients treated by doctors in rural areas and by inexperienced centers had similar in-hospital hemorrhage and mortality rates. The trial showed that "telemedicine" consultations provided more accurate diagnoses and decisions. Therefore, the American Heart Association published guidelines on the use of tPA in acute stroke care. The American Heart Association's guidelines on telemedicine in stroke care are a good start.

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Although the FDA has approved intravenous tPA for acute ischemic stroke, the practice of administering it has created a malpractice risk for physicians. Physicians who refuse to use tPA are subject to medical malpractice litigation. Although tPA is considered a safe and effective treatment for ischemic stroke, it is still significantly underutilized. The risk of malpractice for physicians involved in this practice should not be underestimated.

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The combined therapy was effective for patients with AIS, but the trial did not prove that it is better than tPA alone. Patients with AIS treated with tPA-based therapy had a lower rate of re-occlusion at 24 hours and better functional outcomes at three months. Further research is needed to determine which treatment is best for patients with AIS. So, in order to evaluate the safety and efficacy of tPA, you should consider combining tPA with another therapy.