TPA improved stroke patients' functional outcomes, quality of life

LONDON – Intravenous thrombolysis administered within 6 hours of a stroke resulted in a significantly greater percentage of patients with better functional outcomes and quality of life after 18 months than did standard stroke care in an analysis of secondary endpoints in the Third International Stroke Trial.

At 18 months’ follow-up, a significant overall difference in quality of life on the EuroQoL-5 Dimensions (EQ-5D) instrument was seen in favor of tissue plasminogen activator (TPA) rather than placebo treatment (P = .03).

Furthermore, four out of the five domains measured by the EQ-5D were significantly improved, including mobility (P = .02), self-care (P = .001), usual activities (P = .008), and pain or discomfort (P = .03). The results of the Third International Stroke Trial (IST-3) at 18 months’ follow-up were recently published (Lancet Neurol. 2013;12:768-76).

^{Sara Freeman/IMNG Medical Media}

Dr. Peter Sandercock

"If you survive a stroke, you have to live with it for rather a very long time," said IST-3 chief investigator Dr. Peter Sandercock, who presented these secondary endpoint findings at the annual European Stroke Conference.

"I think this is something that many trials today have forgotten," said Dr. Sandercock, who is professor of medical neurology in the Centre for Clinical Brain Sciences at the University of Edinburgh (Scotland) and director of Edinburgh Neuroscience there. He added that treatments that produce relatively modest improvements in pathological outcomes in the short term might turn out to be cost effective in the long term.

Indeed, few trials in stroke to date have considered the longer-term quality-of-life effects of stroke treatment. The INTERACT2 trial (N. Engl. J. Med. 2013;368:2355-65) recently reported positive findings for blood pressure reduction in intracerebral hemorrhage, Dr. Sandercock noted, but IST-3 is the largest, and first, to report on the long-term benefits of thrombolysis in a stroke population. IST-3 is a randomized, controlled, open-treatment trial of 3,035 patients enrolled at 156 hospitals in 12 countries who were treated with intravenous thrombolysis or placebo within 6 hours of a stroke.

The primary endpoint results of IST-3 were published last year (Lancet 2012;379:2352-63) and showed a similar percentage of patients treated with TPA (37%) or placebo (35%) were "alive and independent" at 6 months, as signified by a score of 0-2 on the Oxford Handicap Scale (OHS). The OHS is similar to the modified Rankin Scale, with lower scores indicating no or minimal functional problems.

Now with longer follow-up out to 18 months, however, a higher percentage of TPA-treated patients had an OHS score of 0-2 (35% vs. 31% for the control group; odds ratio, 1.28; P = .024).

This result equates to an absolute difference of 36 more patients per 1,000 being alive and independent at 18 months if they received thrombolysis, Dr. Sandercock said. At 6 months, the absolute difference was not significant, with 14 more patients per 1,000 being independent if they received thrombolysis.

An ordinal shift analysis of OHS scores at 18 months showed that there was a similar percentage of deaths, at 37% for both treatment arms, but that all other scores were shifted in favor of TPA treatment (OR, 1.3; P = .002).

Of the 3,035 patients who participated in IST-3, 2,348 from 10 recruiting countries were eligible for inclusion in the 18-month follow-on study. Of these, 1,169 were treated with intravenous TPA, and the remainder were given a placebo injection.

Follow-up was by postal questionnaires, 44% of which were completed by a patient and 56% by a caregiver. If there was no response, a telephone-based interview was conducted. The investigators assessed QoL by the EQ-5D, EQ index, and EQ visual analog scale, as well as by an assessment of where the patient was living.

There was a marginal difference in patients’ living situations in favor of TPA treatment, with the agent being administered to 85.1% of patients living at home rather than in an institution versus 83.9% of patients given placebo (P = .05).

Boehringer Ingelheim donated the thrombolytic agent alteplase (Actilyse) to the first 300 patients but had no other role in the study. Dr. Sandercock disclosed that he has served as a speaker for Boehringer Ingelheim.