by John Fauber
Time is brain. Every minute wasted seeking treatment is measured in neuronal death, which is why stroke specialists were early supporters of certified stroke centers. Getting a stroke patient to the right center — a center that could administer clot-busting therapy quickly, and safely — was considered the surest way to “save brain.”
That was the concept behind the certified stroke center movement, but as Sam Denny found out last May, the real world of ischemic stroke treatment does not always mirror the concept.
An Ordinary Day
On Tuesday, May 4, Denny, 56, an executive in commercial real estate development and management, was working in his downtown office. Around 10 a.m. he felt a little lightheaded, but the lightheadedness soon went away and he felt normal, he recalled in an interview.
At 2 p.m., he left for a business meeting and at that meeting he began to have vague symptoms such as a dry mouth. Although he could walk, he realized that it took more effort than usual.
Denny, a diabetic, thought his blood sugar might be low, so after he left the meeting, he stopped to get a candy bar.
When the sensations did not go away he drove himself to a nearby urgent care clinic run by Columbia St. Mary’s Hospital. He arrived at the clinic sometime after 3 p.m.
At the clinic, the doctor said he suspected that Denny might be having a stroke, but after an exam, the doctor concluded that there was nothing wrong and he told Denny to go home.
Denny said he did not feel right and asked to go to Froedtert Hospital, the hospital where his primary care doctor works.
At that point, an ambulance was called to the scene. Denny said both the clinic doctor and the ambulance driver insisted that Denny should be transported to the closest hospital — Columbia St. Mary’s Hospital, which also was certified by the Joint Commission as a Primary Stoke Center.
Primary stroke centers — and the treatment algorithm that is the raison d’être for such centers — have been described in great detail at endless neurology conferences and in scores of scientific publications. Theoretically, these centers are specifically designed for efficacy.
Patient arrives; undergoes physical examination; imaging studies are ordered; ischemic stroke is confirmed; and recombinant tissue plasminogen activator (tPA) is administered.
It was there that Denny’s treatment should have picked up speed.
But, at Columbia St. Mary’s, the wheels fell off the neat “time is brain” scenario.
Denny was not prepped for thrombolysis. The doctors there did not administer tPA.
Michael Connor, MD, a Columbia St. Mary’s neurologist, who spoke on behalf of the hospital after reviewing Denny’s case, said his case was handled properly.
Denny, who is still undergoing rehabilitation to recover from the stroke, isn’t so sure.
Until a couple of weeks ago, Denny needed a cane to help him walk. The cane is now gone, but he struggles daily with fatigue. His goal, Denny says, is to once again play golf. Denny survived and this is certainly good news, but is his remaining disability a function of his stroke or his stroke treatment?
As a stroke patient, Denny’s story is not all that unusual because while a growing number of hospitals boast that they are equipped to deliver brain-saving therapy — and aggressively market themselves as Primary Stroke Centers. A MedPage Today/Milwaukee Journal Sentinel investigation revealed that certification does not guarantee clot-busting therapy.
While tPA is the only FDA-approved drug for treating an ischemic stroke, the number of patients who get tPA has remained dismally low — only about 5% of ischemic stroke patients have received the drug since it was approved 14 years ago.
Is the Window Open?
Often the drug is not used because the patients arrive at the hospital more than 4 1/2 hours after onset of stroke symptoms, which is considered too late for tPA to benefit the patient.
But many patients — like Denny — arrive with time to spare; yet they don’t get tPA.
The precise number of eligible patients seen at Primary Stroke Centers who are not getting the drug is not known, but data suggest it is significant, especially at nonteaching hospitals, which account for most of the centers.
Last year, a study based on data collected by the Joint Commission from stroke centers it certified found that 33% of eligible patients at nonteaching hospitals were not being treated with the drug during the first two years after a hospital had been certified. That number dropped to 26% after four years.
It took up to six years before all eligible patients were getting tPA, and only 21 stroke centers out of 418 certified by the Joint Commission had reached that point.
And that may be a rosier picture than actually exists because much of the Joint Commission data were self-reported by the hospitals and not audited or verified by a third party.
Or that 33% estimate may be high, according to Mark Alberts, MD, a neurologist at Northwestern’s Feinberg School of Medicine in Chicago and a consultant to the Joint Commission who led the survey research. Albert estimated that less than 10% of Primary Stroke Centers are actually not offering tPA to eligible patients.
“There is a small group of bad players, but they need to be called out,” said Ralph Sacco, MD, a neurologist at the University of Miami and neurologist the president of the American Heart Association, said the situation is improving, although more patients need to be treated.
“Yes, there still are doubting Thomases out there,” he said. “I think it is becoming less prevalent.”
Part of the problem is that the Joint Commission does not require hospitals to actually treat a certain level of eligible patients as a criterion for certification as a stroke center. Hospitals only need to demonstrate that they have the ability to offer the drug.
The commission does not look at medical charts and determine if a patient should have received the drug, said Jean Range, RN, MS, executive director of the commission’s certification program for various diseases.
“We don’t prescribe medical process or do peer review,” she said.
The commission also does not release performance data such as the rate of tPA use at individual hospitals.
Barriers to Use
Moreover, some of the under use of the drug is due to legitimate medical differences over how and when to use it.
Because the drug can cause bleeding in the brain in about 5% of cases, some doctors worry about getting sued, even though such cases are rare and a doctor is more likely to be sued for not using the drug, according to stroke specialists interviewed for this story.
Another financial disincentive is the small amount of reimbursement – as little as $200 – neurologists receive when they are called from a busy office practice with waiting patients to the emergency room to decide whether to use the drug, they said.
“You get as much reimbursement for administering tPA as you do burning off warts in a dermatologist’s office,” said Dawn Kleindorfer, MD, a stroke specialist and associate professor of neurology at the University of Cincinnati College of Medicine.
Stroke as a Growth Industry
Stroke is the leading cause of serious disability in the United States. With nearly 800,000 strokes each year and there has been a steady increase in the number of hospitals willing to pay the $4,600 annual fee that the Joint Commission charges for certification as a booming Primary Stroke Center.
And with the growth in stroke centers the issue of tPA use has come into sharp focus.
Good Medicine or Good Marketing?
While the Primary Stroke Center program has helped get the drug to more people, many stroke doctors claim it also is being used as a marketing tool by hospitals.
For example, the Joint Commission offers a publicity kit to certified hospitals and suggests that hospitals use its Gold Seal of Approval in everything from advertising to stationery. It advises hospitals to call news conferences and to invite local reporters in to do interviews with executives.
The Commission also provides a sample press release.
Since 2003, 725 hospitals, including 29 in Wisconsin, have received stroke center certification.
For neurologists who treat strokes and for several major medical organizations, there is no debate about the efficacy of tPA.
Even with a recognized bleeding risk, tPA substantially reduces the risk of disability in patients who are treated quickly.
“It is the best thing we have for acute ischemic stroke,” said the AHA’s Sacco.
Groups such as the Heart Association and the American Stroke Association were so convinced of the drug’s benefits that last year they issued guidelines based on new research extending its use to up to 4.5 hours after the onset of symptoms in certain patients. When tPA, which typically is administered by IV, was approved in 1996, its use was limited to three hours after symptoms began.
The Sooner, the Better
In patients treated within three hours of the onset of symptoms, there is a 32% chance of having a better outcome than without treatment, including a 12% better chance of having little or no disability, said neurologist Jeffrey Saver, MD, director of the UCLA stroke center.
Factored into that is 2% to 3% chance of bleeding in the brain that will cause a worsening of the patient’s condition.
Saver said he tells patients that for every 100 people who are treated, 32 will have a better outcome and three will have a worse outcome as the result of treatment. In the rest, there is no effect.
Yet while the drug is considered safe and effective by the FDA and has been in use since 1996, some doctors – mostly emergency room physicians – remain unconvinced about its effectiveness.
Much of the reluctance to use the drug dates back to the original NIH-funded research done in 1995, said Robert Solomon, MD, a spokesman for the American College of Emergency Physicians.
He said it is just not that impressive and guessed that only 25% of emergency room doctors are enthusiastic about the drug, 25% are skeptical and the rest are “nervous.”
There is no question that those who are treated in less than 90 minutes do better than those who are treated in less than 180 minutes, said Solomon, an ER doctor at the Southwest Regional Medical Center in Waynesburg, Pa.
He said that when he explains the risks vs. benefits of the drug to eligible patients and tells them, “It’s your call,” about half opt not to get the drug.
Solomon, who said he remained a skeptic, acknowledged that when stroke neurologists, who interpret the research differently, explain the risks and benefit a much higher number of patients want the drug.
In fact, the two specialties have battled over whether the drug should even be used.
For several years after the drug was approved, a number of papers from emergency medicine specialists raised concerns about its effectiveness and the risk of bleeding in the brain.
The drug became an advance that disrupted the way medicine was practiced, said neurologist Saver of UCLA.
Neurologists who were not used to acting in emergencies did not want to come into the ER. Radiologists were not anxious to read CT scans in an emergency setting.
“This left emergency doctors holding the bag, caring for patients who had a complex brain disease without adequate support from the brain and imaging specialists,” said Saver, a professor of neurology.
Some of them responded by saying the therapy was unproven, despite FDA approval of the drug, and that ER doctors did not have to give it, which helped protect them from malpractice suits, but left patients in the lurch, he said.
“The whole culture of treating stroke hasn’t caught up with the science,” said Diane Book, MD, medical director of the stroke program at Froedtert Hospital where Sam Denny now is undergoing physical therapy. “It is like trying to move glaciers in changing attitudes. The system tries to find reasons not to treat rather than to treat (with tPA).”
And “the system” appears to be very good at finding those reasons.
Sixty-four percent of hospitals in the U.S. did use tPA at all between 2005 and 2007, according a 2009 study in the journal Stroke. The study looked at the overall use of the drug at 4,750 hospitals and in 495,186 stroke cases. The nonusers tended be smaller facilities or were located in the Midwest and South.
Last November, a report from the CDC found that only 40% of eligible stroke patients received tPA. The study involved 57,000 patients treated between 2005 and 2007 at 195 hospitals in Georgia, Illinois, Massachusetts and North Carolina that were part of a national registry designed to improve stroke care.
At Columbia St. Mary’s, where Denny received his initial treatment, the hospital maintains that it has treated 94% of eligible patients with tPA since it became a Primary Stroke Center in 2006.
Connor said Denny was not offered IV tPA because doctors determined that his symptoms started at 10 a.m., which put him outside the treatment window.
“If this was a clear cut case and we missed it, I’d say, ‘yeah, we’re guilty,'” he said. “This was not a clear cut case. This patient had excellent care at Columbia.”
However, Book, Denny’s doctor at Froedtert Hospital, where he eventually was transferred, said that if he had come to Froedtert from the urgent care facility, she would have offered him IV tPA.
She said his lightheadedness in the morning might not have been a stroke symptom. Beyond that, once that symptom cleared – Denny said he felt normal until after 2 pm. – a new treatment window began, Book said.
“You can say there is a new stroke occurring and the clock restarts,” said Book, an associate professor of neurology at the Medical College of Wisconsin.
However, she said that is a clinical judgment and other doctors might have a different opinion.
Two other stroke specialists contacted by the Journal Sentinel who asked not to be identified offered a similar view on the case.
One doctor said if symptoms go away and the person is back to feeling normal or, better yet, they are examined by a doctor who finds them to be normal, then the clock restarts.
“I have treated a fair number of people with a TIA (transient ischemic attack, the so-called mini-stroke) earlier in the day that resolved, and then the symptoms returned,” the doctor said.
The other doctor said a good argument could be made that the safest thing to do was not offer tPA. However, because Denny’s stroke occurred in the brain stem, it had the potential to be catastrophic, the doctor said. Therefore more aggressive treatment using tPA also was reasonable.
“Two stroke neurologists who are on different ends of the spectrum of favoring or distrusting/hating…tPA can hear these data and come to completely different conclusions and neither one is clearly wrong,” the doctor said.
And Connor said the location of the stroke in the brain did not matter because doctors had already determined that he was outside the window for receiving the drug.
When in Doubt
Physicians interviewed by MedPage Today/Milwaukee Journal Sentinel, agreed there was a bias against using tPA when the presentation is not clear-cut or when other issues-such as insurance-are a consideration.
For example, Justin Sattin, MD, a stroke specialist at the University of Wisconsin – Madison, recalled a case this year involving a veteran who first went to a local hospital where doctors debated whether to treat him with tPA or send him to the VA Hospital. The doctors seemed more interested in where he should go than treating his stroke, said Sattin, an assistant professor of neurology at UW School of Medicine and Public Health.
“Unfortunately it’s not that rare,” he said. “Several times a year we get these folks where it looks like they should have gotten the drug and they did not. And then you get the ones where you go, ‘Oh my gosh, Why didn’t this person get it?'”
Book, of Froedtert Hospital, said she sometimes sees such patients at her hospital after they are transferred there.
“They weren’t even aware it (tPA) was an option,” she said.
Brett Kissela, MD, a stroke researcher and associate professor of neurology at the University of Cincinnati, a nationally recognized stroke research center, said he knows of doctors who are opposed to using tPA, but who go through the motions of Primary Stroke Center certification anyway.
“It’s a shame that people can talk a good game and not go through with it,” he said. “There are several stroke-certified centers that I wouldn’t want to go to.”
Indeed, a 2009 report in the Journal of Brain Disease found that only 48% of emergency room doctors responding to a survey thought tPA was effective and only 52% said they would use it even under ideal conditions. About half of those doctors worked at Primary Stroke Centers.
Denny said doctors at Columbia St. Mary’s spent a lot of time trying to figure out if the treatment window still was open.
He said they asked him if he would be willing to live with the reduced function he was experiencing, which at that moment was not substantial, although it would get dramatically worse a short time later. His wife, Marsha, said they told him there was a 10% chance of serious bleeding in the brain.
She said that within about an hour of being told he was outside the treatment window, his symptoms got much worse.
His face drooped, his speech was unintelligible and he could not move his left hand or leg, she said.
“He was just lying there,” she said.
Later that night, he was transferred to Froedtert Hospital in hopes that doctors there might be able to eliminate the clot by using a device that is threaded through an artery in the groin directly up to the brain.
However, the clot was in a blood vessel that was too small to use the device.
Denny now is undergoing physical therapy at Froedtert and his function has improved dramatically.
He had been walking with a cane until earlier this month.
His biggest problem now is fatigue and a lack of coordination when his muscles get weak. If he walks or even types for more than 10 minutes his left side gets weak.
“I can do almost anything,” he said. “I just don’t have the stamina. I think I’ll be fully recovered in a year.”
In hindsight, he said he is troubled about whether he should have received tPA.
“I’m not dwelling on it,” he said. “It’s not going to do me any good.”
But among neurologists and those who oversee stroke care, the use and possible under use of tPA remains a concern. As a sign of that concern, earlier this year the Joint Commission created a new voluntary measure for the hospitals it certifies as Primary Stroke Centers.
In the past, the commission had collected only self-reported data on tPA use from hospitals. As of January, the organization said hospitals could send that information to an outside party for an independent audit.
So far, only about 20 of the more than 700 Joint Commission certified stroke centers have elected to do so.
John Fauber is a Milwaukee Journal Sentinel/MedPage Today reporter.