Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials

Abstract

Background Since its approval, the use of alteplase had been limited to patients aged ≤80 years. Aims TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. Methods TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0–2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. Results Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69–2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. Conclusions The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.