Pharmacy News

Stroke Guideline Supports Expanded Alteplase Use

[March 15, 2013, AJHP News]

Kate Traynor

BETHESDA, MD 27 Feb 2013—A revised American Heart Association and American Stroke Association (AHA–ASA) guideline on the early management of ischemic stroke seeks to build on recent gains in reducing disability and death from stroke.

According to the guideline, stroke in 2008 was the fourth-leading cause of death in the United States—an improvement from previous years, when the disease ranked third. Further gains, according to AHA and ASA, require a comprehensive approach to caring for patients in the immediate aftermath of a stroke.

A major medication-related recommendation in the guideline is the option to begin therapy with alteplase, a recombinant tissue-type plasminogen activator (t-PA), up to 4.5 hours after the onset of stroke symptoms in certain patients instead of limiting the therapy to within 3 hours after the stroke.

"It's a huge deal. It's definitely going to expand the number of patients that can be treated," said Patrick Bridgeman, emergency department pharmacist at 600-bed Robert Wood Johnson University Hospital (RWJUH) in New Brunswick, New Jersey.

AHA and ASA initially made the recommendation in a 2009 advisory bulletin, but this is the first time the expanded window has been included in the groups' official guideline, which was last updated in 2007.

The administration of alteplase beyond 3 hours after symptom onset is an off-label use of the drug. Bridgeman said having the recommendation in the guideline may increase clinicians' comfort level with the practice.

But he said the neurologists at RWJUH, a Joint Commission-certified primary stroke center, aren't worried about the labeling issue.

Bridgeman said 98 of the approximately 700 patients evaluated last year by RWJUH's stroke team, or 14%, were treated with alteplase.

"We're one of the largest users of t-PA on the East Coast right now," he said.

According to the National Institute of Neurological Disorders and Stroke (NINDS), about 5% of patients nationwide receive reperfusion therapy after a stroke, and only 40% of those are treated within "a useful time frame."

Poor outcomes are common after a stroke even when alteplase is administered. According to NINDS, 30% of alteplase recipients have a "less disabled final outcome," including 12% with little or no disability three months after an ischemic stroke.

Who gets alteplase. Eligibility criteria for alteplase administration include a diagnosis of ischemic stroke causing major neurologic defect in a patient age 18 years or older and onset of symptoms less than 3 hours before initiating alteplase therapy.

A table in the guideline lists 23 absolute or relative exclusion criteria for i.v. alteplase administration within 3 hours of symptom onset. These include heparin therapy within the past 48 hours resulting in an elevated activated partial thromboplastin time; current use of direct thrombin inhibitors or direct factor Xa inhibitors, with specific elevated coagulation test values; or current use of an anticoagulant with an International Normalized Ratio (INR) value of >1.7 or a prothrombin time of >15 seconds.

If the 3-hour window is missed in an otherwise eligible patient, alteplase administration 3–4.5 hours after stroke onset is recommended in some circumstances.

One of the major exclusion factors for alteplase administration during the expanded window is the use of any oral anticoagulant within the past 48 hours, regardless of the patient's INR value.

Alison Jennett-Reznek, clinical pharmacist in emergency medicine at Saint Vincent Hospital in Worcester, Massachusetts, said the risk of major bleeding is a serious consideration when evaluating patients for alteplase administration. Complicating the picture is the lack of a specific antidote to reverse the effects of direct thrombin inhibitors or factor Xa inhibitors.

"There's really no data, no evidence, for what's the best way to reverse the bleeding, and what's the risk of them actually bleeding," she said.

Jennett-Reznek said pharmacists have a vital role to play in the emergency room when a patient arrives after suffering a stroke.

"There are so many things to consider, not just medications," she said. "You as a pharmacist need to also understand the patient's medical history and any other comorbid conditions that they have."

Getting the medication history is important, too, she said. This may require contacting the patient's pharmacy, family, and the emergency medical services team that transported the patient.

The guideline notes that laboratory testing may help clinicians determine whether a patient has recently taken a direct thrombin inhibitor or factor Xa inhibitor. Possible tests include specific assays and evaluations of thrombin time or ecarin clotting time.

But the guideline states that these tests may not be readily available to clinicians, and the decision to administer alteplase should not await the results of coagulation tests.

"A lot of institutions don't have these, so if they're in a rush, they're going to make the decision based purely on medication history," Bridgeman said.

For all patients, the only laboratory test result necessary before initiating alteplase therapy is a glucose-level determination that can be done though a finger stick, according to the guideline. This is necessary to rule out hypoglycemia as the cause of the patient's neurologic defect.

Hospital time counts. Another important new recommendation in the AHA–ASA guideline is that i.v. alteplase administration in eligible patients should begin within 60 minutes of arrival at the hospital. This is referred to as the door-to-needle time, and just over a quarter of hospitals in an analysis cited in the guideline met the goal.

Bridgeman said RWJUH meets this goal nearly 100% of the time.

He said the biggest barrier to meeting the 60-minute goal in the past was waiting for the results of a patient's INR test, which takes about an hour.

"Now we don't even wait for the INR to come back," he said, because treatment is based on the patient's medication history.

NINDS in 2011 began a two-year process to identify high-priority areas for stroke prevention, treatment, and recovery. One major priority is to make reperfusion therapy for ischemic stroke "swifter, safer, and surer" for patients.

As part of this effort, the institute wants the door-to-needle time to approach 30 minutes for a substantial number of patients, as has been reported for some sites in Europe.

Finnish researchers late last year reported achieving a 20-minute door-to-needle time by maximizing evaluations, communications, and interventions before the stroke patients arrived at the hospital. The AHA–ASA guideline describes a similar approach and includes recommendations for ambulance dispatchers and emergency medical service personnel as well as hospital staff.

The guideline also stresses the need to increase awareness among the public about the warning signs of stroke. According to the guideline, most people do not recognize the signs of stroke and wait too long to get help, leading to poorer outcomes.


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