Drug Therapy for Strokes

One Saturday morning last November, Peggy Code collapsed outside a suburban Calgary mall. Helped to a nearby bench, the 64-year-old nurse realized she was drooling and that the entire left side of her body was insensate.

Drug Therapy for Strokes

One Saturday morning last November, Peggy Code collapsed outside a suburban Calgary mall. Helped to a nearby bench, the 64-year-old nurse realized she was drooling and that the entire left side of her body was insensate. "Oh, no, I'm having a stroke," said Code, who knew the symptoms well from her work. An ambulance arrived five minutes later and rushed her to Foothills hospital, where Code worked three days a week. She was immediately sent for a CAT scan, which confirmed that she was an ideal candidate for an anti-clotting drug known as t-PA (tissue plasminogen activator). Within the hour that it takes to administer t-PA intravenously, Code could lift her left leg and arm; by the next morning, she felt no residual effects from the stroke. Although feeling fit, Code, who was due to retire next September, has decided not to return to work. Still, her recovery "was a miracle," says Code, her voice breaking with emotion. "I feel that I'm just so lucky."

As someone who has watched patients spend months, even years, struggling to overcome the physical disabilities inflicted by a stroke, Code takes her good fortune to heart. She benefited from the fact that Calgary is at the centre of an 18-month national trial using t-PA to treat victims of ischemic stroke. That effort follows a 30-month tracking of 68 stroke patients - the largest single sampling to date in Canada - treated at Foothills between April, 1996, and December, 1998. The results of the Calgary study, published last month in the Rochester, N.Y.-based journal Neurology, provide new hope for stroke victims and their families.

Of the patients who adhered to the treatment guidelines for t-PA, 67 per cent recovered to the point that they could function independently - compared with the norm of only 26 per cent when no drug treatment is offered. Observes Alastair Buchan, a leading stroke expert and director of Foothills hospital's acute-stroke program: "If we can convert a patient with a disabling stroke into someone who can walk out of the hospital without assistance, then that's a save."

Under review is not just a new drug, but a radically new way of dealing with stroke victims. Traditionally, Buchan says, stroke has been the "Humpty Dumpty" syndrome ("all the king's horses and all the king's men couldn't put Humpty Dumpty together again"). The brain damage that an average stroke inflicts is so severe that doctors believed little could be done in the way of treatment. But with the advent of t-PA - and the promise of other chemical and surgical interventions on the horizon - all that is changing.

First approved by the U.S. government in 1987 for cardiac disease, t-PA has only recently become available for stroke. The drug literally eats away the protein that causes blood cells to clump together into a stroke-provoking clot. To be effective, though, t-PA must be administered within three hours of the stroke's onset - and that's where the real challenges to the medical community come into play.

In Calgary, health officials have taken the lead by streamlining emergency measures to respond to stroke with the same urgency as serious trauma. The effort was aided by the consolidation, starting in 1995, of the city's three hospitals and a host of other facilities and services into the Calgary Regional Health Authority. In 1996, the new authority decreed that all neurological services be centred at Foothills and that all suspected stroke victims be delivered to that hospital.

A key priority was to ensure that the city's paramedics recognize the first signs of stroke - including sudden weakness down one side, confusion and difficulty of speech - and move the right patients to the right place as quickly as possible. Once patients arrive at Foothills, a triage nurse checks their blood pressure and glucose levels to make sure they are stable, then directs them to a CAT scanner in the emergency room that has been reserved for this purpose. The resulting brain image tells the attending neurologist what kind of stroke the patient is suffering. In about 20 per cent of cases, it will be a hemorrhagic attack, involving bleeding inside the brain, in which case t-PA cannot be used because it could aggravate the problem. Of the remaining 80 per cent of cases - the ischemic strokes - other patients will be ruled out because their stroke is too severe for the drug to do much good or because it is mild enough that they might recover on their own.

If a stroke victim is a candidate for t-PA, and if the family consents, the patient is wheeled to a 15-bed stroke unit, where everything is ready to begin the infusion of the drug. While the outside window for treatment is three hours, Buchan says that, if all goes as it should, patients receive t-PA no later than 90 minutes after the onset of a stroke. "None of this is rocket science," observes Buchan. "It's all about organizing and treating stroke as an emergency."

Starting in February, 1999, Buchan and his associates were also put in charge of collecting information on patients who are being treated with t-PA at other centres across the country. The results of the 18-month trial will determine if Canada upgrades its provisional licensing of t-PA for stroke victims to a formal approval. One aspect that bears close monitoring is that, in some cases, t-PA can induce hemorrhaging, increasing the severity of a stroke and even leading to death. "The risk," says Buchan, "makes us very, very careful."

In the Canadian cases to date, he says, the drug has been shown to increase the risk of hemorrhaging in about four per cent of patients. Results from two separate studies on t-PA usage in the United States, published in this month's Journal of the American Medical Association, peg the increased risk to anywhere from 3.3 per cent to 11 per cent of patients. In many U.S. cases, the higher incidence of hemorrhaging appears to be linked to t-PA being administered outside the prescribed three-hour limit or by physicians without the best experience with stroke and new stroke interventions.

Under the right circumstances, though, t-PA has the potential to be a major new force in combating stroke. Every year, at least 50,000 Canadians suffer a stroke, with a third of them fatal. That makes stroke the nation's third-leading killer, after cancer and heart disease. But stroke is also the number 1 cause of disabilities, with 300,000 or more survivors struggling daily with afflictions ranging from loss of vision or speech to crippling paralysis. On average, a stroke survivor will spend 30 days in hospital and three or four months in rehabilitation. Beyond the individual suffering, strokes exert considerable pressure on health-care resources. The Heart and Stroke Foundation of Canada - which pays Buchan's salary as the country's only professor of stroke research - estimates that it costs a total of $3 billion a year to deal with the aftermath of stroke.

For people like Peggy Code, the benefits are tangible. Instead of spending this past Christmas languishing in a hospital or in rehabilitation therapy, Code cooked dinner at home for 15 guests, then headed off for a two-week holiday in California with her husband, Bill. "It's been absolutely amazing," says Code. "Life is good." As new medical advances are showing, sometimes Humpty Dumpty can be put back together again.

Maclean's March 20, 2000