Some of the reasons clinical trials with IV-tPA excluded older patients included impaired rate of tPA clearance, increased rate of cardioembolic strokes, and the presence of amyloid angiopathy that could increase the rate of SICH [6
]. Mortality rates and the proportion of moderate or severe functional impairment after an acute ischaemic stroke are higher in the elderly [12
]. In general, the series of patients older than 80 years treated with IV-tPA have had increased mortality, and the proportion of patients with good functional outcome was smaller in comparison with younger patients [6
]. Furthermore, Sarikaya et al. [27
] have suggested less favourable outcomes in nonagenarians as compared with octogenarians after IV-tPA. However, very recently, the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) has provided the largest amount of data on the safety and outcome in thrombolysis in patients >80 years of age. This group concluded that these patients had a similar rate of SICH, and the higher mortality and the poorer functional outcomes were consistent with the overall worse prognosis seen in the natural history of this age group; therefore, patients in this age group are appropriate candidates for thrombolysis [25
]. Moreover, this group performed an adjusted controlled comparison of outcomes between stroke patients who underwent thrombolysis through the SITS-ISTR, with untreated stroke patients from neuroprotection trials held within the Virtual International Stroke Trials Archive (VISTA). Although increasing age is associated with a poorer outcome, the association between thrombolysis treatment and improved outcome is maintained in very old patients [25
]. Mateen et al. [26
] compared the outcomes of thrombolysis in octogenarians and nonagenarians and found that there were no significant differences in functional outcome or rate of SICH.
Our analysis of prospectively collected data indicates that a small cohort of very old patients were treated using thrombolysis (7% of all patients treated). One possible explanation is that our registry started in 2004, when information about IV-tPA in old patients was scarce. The majority (78.3%) of older patients were treated in the last two years of the registry. Alshekhlee et al. [23
] also found very low rates of thrombolysis among very old patients and a trend of increasing IV-tPA use in this age segment over the recent years.
Our results show that a large proportion of OO patients treated with IV-tPA were functionally independent at 90 days (40.2%), although this figure was significantly higher in the group of patients <85 years (58.7%). Furthermore, the mortality rate was higher in the elderly group (28%). As we can see in our multivariable analysis, the worse functional recovery can be explained by confounding factors, whereas mortality was worse in the OO, despite adjustment. We feel that this fact is due the expected major fragility of this age group. Pneumonia was the most common cause of death in the OO group. The rate of SICH in both groups was similar. We did not find any significant differences in the times of management of the stroke inside the hospital, and only stroke-onset-to-door time was significantly longer when compared to the total group of the registry.
This study has several limitations. First, it reports the results of a small cohort of very old patients, and the cohort was compared with a more numerous cohort of patients < 85 years old. Second, the study is a post hoc analysis of a registry, and selection bias is an important limitation to the data set. The decision to administer IV-tPA was made by multiple different treating neurologists, and some factors, not limited to age and prior functional status, could bias treating very old patients with IV-tPA. Finally, the main limitation of the study is the lack of a concurrent untreated control group.
This study supports the use of thrombolytic treatment for very old patients, with safety results similar to younger patients. Although OO patients may have a higher mortality at three months, they still do better than those who do not receive IV-tPA.
As evidence of safety of thrombolysis in very old is increasing, more elderly patients are now treated with IV-tPA. However, reliable evidence on the risk-benefit balance of intravenous thrombolysis in this age group can only be evaluated using randomised controlled thrombolysis trials, such as the ongoing Third International Stroke Trial or the Thrombolysis in Elderly Stroke Patients [35