True believers in the oft-debated tPA are pushing to expand the treatment window yet again
Indication creep seems to be the natural course for medical advancement in the United States. The FDA gives an inch of approval, and we take a mile. tPA is no different. But this article is not about the controversy surrounding the efficacy and safety of tPA. The issues with tPA have gone way beyond professional disagreements about efficacy, safety and time windows.
Two areas of indication creep are becoming common if not pervasive. They focus around consent, and identification of symptom onset, the “wake up stroke.”
All too often, an overzealous physician or hospital administrator will confuse the concepts of standard of care and informed consent. We’ll save the debate about whether or not tPA is the standard of care in ischemic stroke for another day. What is important to recognize is that whether tPA is the standard of care or not is completely irrelevant with respect to the need to obtain informed consent to deliver it. What used to be the few has grown to the many who believe that “because tPA is the standard of care” informed consent is not necessary. This assertion is rooted in a fundamental misunderstanding of the law and a lack of regard for patient autonomy and decision-making. Don’t patients have the right to decide what is best for them? Aren’t they entitled to a full explanation of the risks and benefits of a proposed treatment so that they can make an informed decision?
The standard of care is generally defined as what a reasonable provider with similar training, in similar circumstances, would do. In short, it is based on the reasonableness of the provider’s actions. Not withstanding that there are standards of care to be met with obtaining consent, these are generally unrelated concepts.
Although a bit of an oversimplification, informed consent is necessary when the risks and benefits are not intuitive to the patient. When a patient presents to the ED for a laceration repair, we don’t obtain consent for the repair, as a reasonable patient is expected to understand that the wound will be anesthetized, cleansed and repaired. However, if procedural sedation is deemed necessary, informed consent should be obtained for the sedation, as with this the risks and benefits are not well known. A reasonable patient is not expected to understand the nuances without explanation. In contrast to lacerations, the decision to deliver tPA is, perhaps, one of the most complex decisions a clinician is faced with. If the decision is so complex for us, with so much controversy remaining over the interpretation of the evidence, how in the world do we think patients can make a rational decision without being fully informed first?
Affirming that this decision is incredibly complex, some physicians have gone the perplexing route of taking matters entirely into their own hands – not obtaining informed consent. Acknowledging the complexity of this very important decision should emphasize the need for an informed discussion, not take away the opportunity for patients to decide their own fate.
Some feel so strongly about tPA that they believe no reasonable patient would ever choose not to accept it. “If informed refusal, the patient wasn’t appropriately informed.” (Liang, B.A., et al, Review Of Tissue Plasminogen Activator, Ischemic Stroke, And Potential Legal Issues. Arch Neurol 65(11):1429, November 2008.) Just because you might want tPA has no bearing on whether or not your patient should be given the opportunity choose.
The “Wake up stroke” (WUS) is a concept that is slowly gaining momentum with tPA supporters. In short, why should patients who wake up with their symptoms be disallowed the benefit (or potential harm) of tPA? Those who are asking this question are often supportive of the concept that if you wake up with your symptoms, forget the time frame (0-3 or even 4.5 hours). You’re eligible. This is truly a case of indication creep. Assuming for a moment that tPA were completely safe if given during the NINDS or ECASS-III defined time frames, why do some feel empowered to disregard these strict time lines if a patient was asleep during the onset of their stroke? Most of us sleep for 6-8 hours. Unless someone woke up after a 20-minute catnap, there is no way to determine how long they have had their symptoms. Thus, the time window could easily be extended to 6 or 8 hours if the WUS concept is adopted. The leap of faith taken with this concept is truly amazing.
Barreto’s study group concluded the following about WUS patients receiving tPA:
“Thrombolysis may be safe in WUS patients. Our center’s experience supports considering a prospective, randomized trial to assess the safety and outcome of thrombolysis for this specific patient population.” However, 15% of WUS patients who received tPA died, compared to none of those not receiving tPA. (Barreto AD, et al. Thrombolytic Therapy for Patients Who Wake-Up With Stroke; Stroke. 2009;40:827-832.)
A second study, published in 2012, also retrospectively reviewing registry data, reported a reduction in mortality for those WUS patients treated with tPA versus those treated within 4.5 hours. However, this difference was not statistically significant. (Manawadu D, et al. Abstract 56: Thrombolysis in Selected Patients with Wake Up Stroke is Feasible with Similar Safety as Thrombolysis in 0-4.5 Hours; Stroke. 2012; 43: A56).
These were retrospective reviews with small numbers of patients. They don’t reflect safety or efficacy, just the fact that despite the existence of well-established eligibility criteria (administration time frames), some clinicians ignore the recommended guidelines to give this drug to patients who were never intended to receive it.
The decision to administer tPA to ischemic stroke patients is often complicated by physician bias. Those who are non-believers are biased against delivery, while those who are zealots for its use strongly favor delivery. Bias, based on critical appraisal of the literature, is expected and reasonable. However, when bias is so great that it empowers physicians to make decisions for others or offer tPA to populations that have never been studied in a randomized, controlled trial, the rules have been more than bent.
Some feel so strongly about tPA that they believe no reasonable patient would ever choose not to accept it. According to a 2008 piece on the subject in Archives of Neurology*, “If informed refusal, the patient wasn’t appropriately informed.” Just because you might want tPA has no bearing on whether or not your patient should be given the opportunity choose.
*Liang, B.A., Et Al, Review Of Tissue Plasminogen Activator, Ischemic Stroke, And Potential Legal Issues Arch Neurol 65(11):1429, November 2008.