IV Thrombolysis Effective in Very Elderly Stroke Patients


SAN ANTONIO — Intravenous infusion of a thrombolytic drug helped octogenarian ischemic stroke patients as much as it did middle-aged adults with stroke in a meta-analysis of data collected from more than 1,700 very elderly patients.

Octogenarian stroke patients “show significant benefit” from intravenous treatment with recombinant tissue plasminogen activator (rt-PA) and no excess harm compared with younger patients, Dr. Kennedy R. Lees said at the conference. The results showed “no diminution of efficacy with age. We have consistent evidence to disregard age when treating ischemic stroke patients with rt-PA,” he said.

Furthermore stroke patients aged at least 75 years are also, in general, the best candidates for rt-PA treatment, according to data from a second independent report at the conference.

Analysis of 1,774 adult ischemic stroke patients who presented to the emergency department at the University of Cincinnati in 2005 showed that the percentage of patients eligible for acute treatment with intravenous rt-PA reached the highest level, 10%, in patients 85 or older; 75- to 84-year-old patients comprised the subgroup with the next highest percentage of good rt-PA candidates, 9%. These rates compared with an 8% eligibility level for all adult stroke patients in the study, Dr. Dawn O. Kleindorfer said of the second report.

“We were surprised to see eligibility increase with age. It's because as patients get older they have more severe strokes,” said Dr. Kleindorfer, director of the division of vascular neurology at the University of Cincinnati.

Strokes too mild to warrant rt-PA treatment made many younger adults ineligible for intravenous treatment, the analysis showed.

Despite this new evidence of the appropriateness, efficacy, and safety of rt-PA in patients aged 75 and older, this demographic subgroup stands out as undertreated with intravenous thrombolytics.

“There is a bias at the bedside of a 90-year-old patient,” Dr. Kleindorfer said in an interview. The evidence suggests that physicians weigh factors differently for very old patients. … In the United States, we place no upper age limit [on rt-PA treatment of stroke patients], but I think there still is inherent tentativeness for treating extremely elderly patients.”

To assess the efficacy of rt-PA in octogenarians, Dr. Lees and his associates used data collected in the Virtual International Stroke Trials Archive (VISTA), a compilation of data from more than 20 stroke trials that involved more than 15,000 patients (Stroke 2007;38:1905–10).

VISTA contained data for nearly 10,000 patients who were enrolled in neuroprotection trials and had a stroke during 1998–2007. Narrowing the database down to ischemic stroke patients with complete follow-up assessment by a modified Rankin scale score yielded nearly 6,000 patients, including almost 1,200 patients who were older than 80. The total group included 1,703 patients who received intravenous rt-PA and 4,114 who didn't receive intravenous thrombolysis.

Among the octogenarians, treatment with intravenous rt-PA led to a statistically significant 34% improvement in outcomes in an analysis that adjusted for age and baseline NIH Stroke Scale score. This relative benefit closely matched the 42% benefit from rt-PA seen in patients younger than 80, said Dr. Lees, professor of cerebrovascular medicine at the University of Glasgow (Scotland).

To analyze rt-PA eligibility, Dr. Kleindorfer and her associates used data from 1,774 adults with ischemic strokes who presented to the emergency department at the University of Cincinnati during 2005. Their average age was 70, and 142 patients (8%) were judged eligible for intravenous rt-PA treatment based on Dr. Kleindorfer's retrospective review of the patients' records. Seventy-two of the rt-PA–eligible patients actually received the drug.

Among the more than 1,600 patients judged ineligible for rt-PA treatment, the most common reason, in 77%, was that their time at presentation exceeded the 3-hour time window for intravenous rt-PA treatment that existed in 2005. (The American Stroke Association last year issued guidelines that expanded the rt-PA treatment window to 4.5 hours after stroke symptom onset). Two other common reasons for ineligibility for rt-PA were a mild stroke with an NIH Stroke Scale score of less than 5, which applied to 58% of the patients, and blood pressures that were too high, in 15% of patients. (The percentages add up to more than 100% because some patients had two or more reasons for not being eligible.)

The extent of patient eligibility and the actual rate at which eligible patients received rt-PA varied significantly by age (see chart). The overall pattern of increased eligibility for rt-PA with increased age, and decreased treatment with rt-PA with increased age were both statistically significant, Dr. Kleindorfer said. The analysis also showed that patients aged 75 or older had a significantly higher rate of an international normalized ratio above 1.6, a legitimate reason for rt-PA ineligibility. But those patients also had a significantly higher rate of more severe strokes that qualified them for rt-PA treatment.


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