Outcomes of basilar artery occlusion in patients aged 75 years or older in the Basilar Artery International Cooperation Study

Patients with an acute basilar artery occlusion (BAO) have a high risk of long-lasting disability and death. Only limited data are available on functional outcome in elderly patients with BAO. Using data from the Basilar Artery International Cooperation Study, we aimed to determine outcomes in patients ≥75 years. Primary outcome measure was poor functional outcome (modified Rankin scale score 4–6). Secondary outcomes were death, insufficient vessel recanalization (defined as thrombolysis in myocardial infarction score 0–1) and symptomatic intracranial hemorrhage (SICH). Patients were divided into four age-groups, based on quartiles: 18–54, 55–64, 65–74, and ≥75 years. Outcomes were compared between patients ≥75 years and patients aged 18–54 years. Risk ratios with corresponding 95 % confidence intervals (CI) were calculated and Poisson regression analyses were performed to calculate adjusted risk ratios (aRR). We included 619 patients [18–54 years n = 153 (25 %), 55–64 years n = 133 (21 %), 65–74 years n = 171 (28 %), and ≥75 years n = 162 (26 %)]. Compared with patients aged 18–54 years, patients ≥75 years were at increased risk of poor functional outcome [aRR 1.33 (1.14–1.55)] and death [aRR 2.47 (1.75–3.51)]. Nevertheless, 35/162 (22 %, 95 % CI 15–28 %) of patients ≥75 years had good functional outcome. No significant differences between age groups were observed for recanalization rate and incidence of SICH. Although patients ≥75 years with BAO have an increased risk of poor outcome compared with younger patients, a substantial group of patients ≥75 years survives with a good functional outcome. Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6498-2) contains supplementary material, which is available to authorized users.


Introduction
Patients with an acute basilar artery occlusion (BAO) have a high risk of long-lasting disability and death [1,2]. Although higher age, analyzed as a continuous variable, has been associated with poor functional outcome after BAO, only limited data are available on functional outcome in elderly patients [3][4][5][6][7][8]. One small case series suggested that all patients C75 years have poor functional outcome [6]. In another study, the eldest surviving patient in whom recanalization was successful was 63-year-old [3]. We analysed data from the Basilar Artery International Cooperation Study (BASICS) to determine outcomes in patients with BAO C75 years.

Methods
BASICS is a prospective, observational, registry of 619 consecutive patients C18 years with an acute symptomatic BAO [2,9]. The protocol was approved by the ethics committee of the University Medical Center Utrecht, the Netherlands. Embolic BAO was defined as complete recanalization on follow-up and no indication of dissection, or maximum deficit from onset and cardiac or vertebral source of embolism, or maximum deficit from onset with complete absence of other atherosclerotic cerebrovascular lesions. Atherosclerotic BAO was defined as known symptomatic basilar artery stenosis ([50 %) prior to occlusion, or residual stenosis after recanalization and no evidence of cardiac or vertebral artery source of embolism, or prior TIAs or stroke in the basilar artery territory and no evidence of cardiac or vertebral artery source of embolism. Dissections were not predefined, but scored according to the investigators.
Primary outcome was poor functional outcome after 1 month [predefined as modified Rankin scale (mRS) score [4][5][6]. Secondary outcomes were death, insufficient vessel recanalization [defined as thrombolysis in myocardial infarction (TIMI) score 0-1] and symptomatic intracranial hemorrhage (SICH). We also investigated if our conclusions changed if poor functional outcome was defined as an mRS of 3-6. SICH was not predefined by the registry, and the reporting of SICH was done on the basis of each investigator's judgment. For the purpose of this study, patients were divided into four age-groups, based on quartiles: 18-54, 55-64, 65-74, and C75 years. Outcomes were compared between patients C75 years and patients aged 18-54 years. Risk ratios (RR) and corresponding 95 % confidence intervals (CI) were calculated. Variables that affected the crude risk ratio most were used simultaneously in Poisson regression analyses to calculate adjusted risk ratios (aRR) [2]. Missing baseline data (\5 % for each variable) were imputed with regression imputation [10]. Finally, we explored the incidence of poor functional outcome in patients 75-79, 80-84, 85-89, and 90 years or older.

Results
Baseline characteristics are listed in Table 1. In total, 162 patients (26 % of total cohort) were C75 years. In this group of patients, the most common cause of stroke was embolism and 64 % had an NIHSS score [20. Treatment of any kind was initiated in 148 patients (91 %).
Modified Rankin Scale scores for all age groups are presented in Fig. 1. Patients C75 years had a higher risk of poor functional outcome [aRR 1.33 (1.14-1.55),  an NIHSS score of 21 on admission. This patient was treated with intravenous recombinant tissue plaminogen activator (rtPA) only, and had an mRS score of 2 at 1 month follow-up.

Discussion
The BASICS study shows that patients C75 years with BAO have an increased risk of poor functional outcome and death compared with younger patients, despite comparable recanalization rates. In contrast with a small previous study [6], our data show that a substantial group of patients C75 years survives with good functional outcome. Previously, it has been suggested that the increased risk of poor functional outcome in elderly patients resulted from a higher prevalence of atherosclerotic occlusions and consequently lower recanalization rates [3]. However, in our study population patients C75 years were more likely to have an embolic rather than an atherosclerotic cause of BAO, mainly due to a higher prevalence of atrial fibrillation. Patients C75 years with an embolic cause of BAO had a similar risk of poor functional outcome compared with patients in this age group with an atherosclerotic cause of BAO. Sufficient recanalization was achieved in 71 % of patients in this age group.
In patients C75 years, several baseline-and treatmentrelated characteristics were associated with an increased risk of poor functional outcome. A recent large case series of patients with BAO, in which only a minority of patients was C75 years, identified similar risk factors for poor functional outcome and death [7].  The strength of this study is that BASICS was a prospective registry of consecutive patients, and therefore our results are representative for daily practice. A limitation of this study is that this was a post hoc analysis of non-randomized data, and therefore the data regarding treatmentdependent outcomes are prone to bias. Due to the prospective collection of detailed data, we were able to perform Poisson regression analyses to adjust for important confounding baseline characteristics.
We conclude that a substantial group of elderly patients survives with a good functional outcome. This study cannot answer the question which treatment option is superior in elderly patients, nor can it define an upper age limit above which treatment is no longer effective. These and other questions may be answered in the recently started BASICS trial in which patients with BAO of up to 85 years of age are randomized between intravenous thrombolysis (IVT) alone vs. IVT followed by additional intra-arterial therapy (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC= 2617; accessed February 1, 2012).