The relatively low U.S. rates of intravenous tissue plasminogen activator therapy for acute stroke may be due in substantial part to widespread use of additional eligibility restrictions beyond the product labeling, Fern Cudlip said at the International Stroke Conference sponsored by the American Heart Association.
Her national survey showed that 81% of U.S. certified stroke centers employ additional inclusion and exclusion criteria not contained in the TPA (Activase) labeling.
Fern Cudlip of Castro Valley, CA
"The use of additional exclusion criteria is so common that it implies perhaps there’s a tendency to try to find a reason not to treat," observed Ms. Cudlip, a nurse practitioner who is stroke program coordinator at Eden Medical Center, Castro Valley, Calif.
Her proposed solution: Organizations that certify stroke centers should require adherence to the TPA-label–defined treatment criteria as a means of improving the nation’s low intravenous TPA treatment rates.
The impetus for the national survey presented by Ms. Cudlip was a sense of frustration that 16 years after Food and Drug Administration approval of intravenous TPA as the first and to date still the only proven therapy for acute stroke, treatment rates remain lower than in many other countries. That’s the case even though access to treatment is better than ever, since there are now more than 900 certified U.S. stroke centers.
In talking informally with colleagues around the country, Ms. Cudlip said she and her coinvestigators realized that many hospitals tack on additional nonstandard requirements for intravenous TPA beyond those specified in the labeling. The investigators decided to document these practices.
Representatives from 229 stroke centers in 43 states and Washington, D.C., completed the 15-minute survey. Sixty-nine percent of the stroke centers were located in community hospitals; the other 31%, in academic medical centers. The centers handled an average of 374 ischemic stroke patients per year, with an overall 8.7% intravenous TPA treatment rate. The rate was significantly higher in academic centers: 10.8%, compared with 8.0% in stroke centers in community hospitals.
The survey questions on nonlabel inclusion and exclusion criteria were restricted to patients who present within the 3-hour treatment window opening at stroke onset. For patients who present within 3 hours, 35% of stroke centers impose as an additional treatment criterion a National Institutes of Health Stroke Severity (NIHSS) score of at least 4, and 26% of centers will give intravenous TPA only if CT angiography shows an occlusion. Neither of these inclusion restrictions are part of the product labeling.
Numerous exclusion criteria beyond the TPA labeling are in use. For example, 44% of stroke centers won’t administer intravenous TPA to a patient who presents within 3 hours of stroke onset if the patient shows rapid improvement, even though a disabling deficit remains. Thirty percent exclude from treatment those patients with an NIHSS score greater than 22; a concurrent acute MI is a contraindication to intravenous TPA at 26% of stroke centers; 22% exclude patients on any form of anticoagulation, regardless of the coagulation laboratory results; 20% exclude patients with a suspected but unwitnessed seizure; 16% routinely exclude patients over age 80; 14% exclude patients with a large-vessel occlusion deemed amenable to intra-arterial therapy; 7% won’t treat a patient on nicardipine for blood pressure control; and 5% won’t treat an otherwise-qualified patient who is on dual-antiplatelet therapy.
The number of nonstandard inclusion and exclusion criteria in place at a stroke center showed a significant inverse relationship with the institutional intravenous TPA treatment rate. Smaller community hospitals with lower ischemic stroke admission volumes tended to have a longer list of nonstandard treatment criteria, according to Ms. Cudlip.
Several audience members rose to voice frustration at the list of off-label impediments to prompt intravenous TPA therapy at their home institutions. One physician, noting that institutional change can be difficult to achieve, asked Ms. Cudlip which two common nonlabel treatment criteria she’d make her top priority for elimination.
Ms. Cudlip answered without hesitation: The requirement that a patient has to have an NIHSS score of 4 or more, which according to her survey is in use at more than one-third of stroke centers, needs to go.
"I can have an NIHSS score of 3 and yet have completely lost my speech. That’s pretty disabling, right? I’d really want you to treat me. I need to speak," she said.
The other widely used nonlabel criterion Ms. Cudlip would target for elimination immediately is the treatment exclusion for patients with rapidly improving symptoms despite a remaining disabling deficit.
A physician audience member chimed in that he finds particularly disturbing the policy of not treating patients over age 80, which is in place at 16% of stroke centers. Ms. Cudlip was fully on board with getting rid of that restriction, as well.