By Charles A. Pilcher MD FACEP
February, 2014
This newsletter has published 4 previous “Perspective” essays on the standard of care for management of acute stroke. One of those standards is the use of tPA (alteplase, or tissue plasminogen activator), the “clot-buster drug,” in those patients presenting within the (now) 4 1/2 hour window from the time they were “last seen normal.” The American College of Emergency Physicians has published a “Guideline” on the subject, recommending that use of the drug be “considered” and every patient “offered” the medication. While less than a ringing endorsement, tPA is the current standard of care. (Other treatment modalities exist, such as mechanical extraction of an obstructing clot, but those will be covered in a future “Perspective.”)
I monitor the literature on this subject assiduously, and have been wondering why I have seen zero news in the past 3-4 years about lawsuits for failure to treat an acute stroke with tPA. Are emergency physicians just better at diagnosing stroke and treating appropriate patients early? Are patients being better informed of the various risks, benefits and contraindications to the drug? Or are plaintiff attorneys now aware of the difficulty in proving causation if the drug is not used?
I believe the answer to be a combination of the above, plus other factors, but clearly lawsuits on the subject are not making news.
The data on the use of tPA in stroke is definitely mixed. The drug has been criticized by several highly regarded specialists in the field. Most of the data in support of the drug’s use have been provided by researchers and institutions whose ties to the manufacturer are clear – or are supposed to be) And the objectivity of Genentech, alteplase’s manufacturer, in the conduct of studies and marketing of the drug has billions of dollars in revenue at stake and has contributed over $10,000,000 to the American Heart Association, developer of the “Brain Attack” guidelines recommending its use. Finally, there has been enough angst among emergency physicians regarding ACEP’s even less-than-ringing endorsement of tPA that the organization is reviewing the matter – only a year after adoption of the policy. And the Society for Academic Emergency Medicine, while rescinding its previous policy against the use of tPA in the ED in 2009, has not yet approved a policy supporting its use.
An attorney client recently brought to my attention a June, 2009, decision from the 5th Circuit Court of Appeals on a case out of Texas that may partially explain the dearth of tPA lawsuits in stroke cases since that date. In that case, against Memorial Hermann Hospital in Houston, a 37 year old man suffered an acute stroke and was seen in the ED in a timely manner but not treated with tPA. The family sued, but the hospital won an MSJ on plaintiff’s failure to provide evidence that the drug would have likely resulted in a superior outcome. At the time, the experts for the plaintiff appear to have relied primarily on the original 1995 study from the National Institute of Neurological Diseases and Stroke (NINDS) for their case.
The 5th Circuit found the following:
[The] plaintiffs in a medical malpractice or health care liability suit must show a “reasonable medical probability” that “their injuries were caused by the negligence of one or more defendants.” This “mean[s] simply that it is ‘more likely than not’ that the ultimate harm or condition resulted from such negligence.” The Supreme Court of Texas, like many courts, has equated the “more-likely-than-not” causation requirement to a more than 50% probability that a defendant’s wrongful conduct caused the harm or injury.
The court, using the same data from the NINDS study as the trial court used, noted that 58% of the patients treated with placebo had an unfavorable outcome, and 41% of the patients treated with t-PA had an unfavorable outcome. Thus, an unfavorable outcome can be expected in only 17% fewer patients treated with tPA than those not treated. [Editor’s Note: I tip my hat to the jurists who recognized the difference between absolute and relative risk reduction.] Clearly, this difference does not meet the requirement of a “50% probability that [the] defendant’s wrongful conduct caused the harm or injury.”
While the standard of care remains that tPA should be “considered” and “offered” to patients with an acute stroke, the data provides little if any support for those plaintiffs attempting to prove causation.
More recent studies have not resolved the dispute. In fact, the website thennt.com summarizes the 12 major studies of the drug and reaches the following conclusions:
No benefit:
- MAST-I
- ECASS-1
- NINDS-1
- DIAS-2
- ECASS-2
- IST-3
Stopped early:
- MAST-E (Deaths 9%)
- ASK (Deaths 16%)
- Atlantis-A (Deaths 16%)
- Atlantis-B (Deaths 4%)
Some benefit:
- NINDS-2 (12% disability benefit, no mortality benefit)
- ECASS-3 (8% disability benefit, no mortality benefit)
[Editor’s Note: Here’s the slide of the above that was shown at ACEP’s Scientific Assembly in Seattle in October, 2013.]
There may still be hope for plaintiff attorneys – and reason for caution by the defense – in those states where “loss of chance” or “loss of opportunity” may be included in a medical malpractice suit. In those states causation does not apparently require the 50% plus caveat, so a plaintiff might have a better chance to prevail. But even so, defendants will have little difficulty finding high-powered academic experts with impeccable credentials [and often an astounding hourly fee] who can effectively argue that tPA should never be used.