Intravenous Thrombolysis with Rt-Pa in Acute Stroke Patients Aged ≥ 80 Years

Thrombolysis with intravenous (i.v.) rt-PA administered within 3 h of symptom onset is the only proven effective reperfusion treatment for acute ischemic stroke. Alteplase was approved in the United States in 1996 and in Canada in 1999. The current European licence, given by the European Medicines Evaluation Agency in 2002, based on the strict eligibility criteria, limits the use of rt-PA to patients aged o80 years. This is due to the lack of clear evidence of safety and efficacy of this treatment in the elderly as most randomized clinical trials (RCTs) on thrombolysis in acute ischemic stroke excluded or underrepresented patients over 80 years. The reasons for this exclusion are several: the highest prevalence in the elderly patients of comorbidities with relative contraindications to thrombolysis, their presumed poorer outcome and major risk of symptomatic intracerebral hemorrhage (SICH) occurrence. But it is well known that the incidence of stroke increases exponentially with age (1). Life expectancy has increased over the past few decades, and the elderly is the fastest-growing component of the population worldwide and particularly in the western world, and it is expected to further increase in the next few years. Moreover, age is an important independent predictor for poor outcome after ischemic stroke, with a larger proportion discharged to long-term institutional care, with relevant financial implications on both health and social care system. For all these reasons, this subgroup of patients might benefit more from thrombolysis. Hence, safe implementation of this therapeutic approach also in the elderly would be an issue of utmost relevance for which clearer data are urgently required. We have few evidence from RCTs. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial (2) part I had an age limit that was subsequently removed in the second part of the study. Since then, only 42 patients over 80 years of age were included. Analysis of the data from the NINDS trial reported the efficacy of rt-PA for acute ischemic stroke independently of the subgroups, and therefore no threshold value for age was identified (3). Most phase IV studies on thrombolysis (4) included elderly patients without an age limit. None, however, stressed specifically the issue of the thrombolytic treatment in the elderly. In the last few years, some open studies on i.v. thrombolysis have addressed the issue of treatment in older patients, with controversial results. A recent systematic review (5) selected some of these cohort studies collecting data on 2244 patients, of whom 477 (ranging from 12 to 31% in the different studies) were aged Z80 years. In a few studies, the older patients were less likely to recover favorably as compared with the young patients. In other studies, there was no difference among age groups. All these studies have discrepancies due to the lack of homogenous baseline characteristics between the two age groups. Furthermore, the definition of SICH varied among the studies, being defined as any kind of CT/MR-documented hemorrhage, in some studies concomitant with an increase of Z4 points in the NIHSS score or in-hospital death, in other studies associated with any clinical deterioration. Therefore, these studies do not allow to draw any conclusion about the effectiveness of thrombolysis. However, they seem to suggest that older patients have less likely a favorable functional outcome (OR 0 53; 95% CI 0 42–0 66; Po0 001), a higher mortality rate (OR 3 09; 95% CI 2 37–4 03; Po0 001) and a similar risk of SICH (OR 1 22, 95% CI 0 77–1 94; P 5 0 34) as compared with younger patients. Data from an Italian cohort of patients confirmed these results (6). Intra-arterial (i.a.) thrombolytic studies comparing outcomes in the very elderly to younger patients yielded encouraging results (7), similar to those of observational i.v. thrombolysis studies, but further studies are needed to better explore the use of i.a. thrombolysis in the very old. Recently, it has been suggested that new neuroimaging methods could be useful for a better and safer selection of the elderly patients likely to benefit from thrombolysis. In fact, in a recent study none of the patients aged Z80 years selected by multiparametric MR for thrombolysis had an SICH, even if there was no decrease in the in-hospital mortality or an improvement of the clinical outcome compared with the patients not screened with MRI (8). Correspondence: Danilo Toni , Unit di Trattamento Neurovascolare, Department of Neurological Sciences, University of Rome ‘La Sapienza’, Viale del Policlinico 155-00161, Rome, Italy. Tel: 139 06 4997 9595; 139 06 4997 9529; Fax: 139 06 4997 9526; e-mail: danilo.toni@uniroma1.it