Changes in survival and characteristics among older stroke unit patients—1994 versus 2012

2.1 Study setting and participants

Akershus University Hospital is situated in the Oslo greater metropolitan area and serves approximately 10% of Norway's population. National policy is to admit all suspected strokes as early as possible and without prior medical examination. Emergency medical services are publically funded in Norway; therefore, patients within the catchment area are admitted to the hospital without any prior selection. Data on consecutive stroke admissions to the SU were prospectively collected from 1 March 1994 to 31 December 1995 (the 1994 cohort), and from 15 February 2012 to 15 March 2013 (the 2012 cohort). The 1994 cohort forms one arm of a quasi-randomized, controlled study investigating the effect of SU versus general medical ward care (Ronning & Guldvog, 1998a, 1998b) and is described elsewhere (Ronning & Guldvog, 1998b). The 2012 cohort is a subset of the Norwegian Stroke—Paths of Treatment (NOR-SPOT) cohort (Barra, Simonsen, & Dahl, 2016), collected to investigate delivery of health services to Norwegian stroke patients. NOR-SPOT includes all admissions to the dedicated SU, plus the few additional stroke patients admitted elsewhere due to overcrowding, but received treatment by the same stroke physicians regardless.

The inclusion criteria used in 1994 were applied to the 2012 cohort for comparability: Patients were included if they received SU treatment, were discharged with a diagnosis of stroke, presented within 24 hr of symptom onset (one calendar day in 2012), and were aged ≥60 years.

The WHO definition of stroke (WHO Task Force on Stroke and other Cerebrovascular Disorders, 1989) was used; however, patients diagnosed with stroke but with symptom resolution within 24 hr due to treatment with intravenous thrombolysis were still classified as having stroke (five cases). Both first-ever and recurrent strokes were included, but only the first admission during the study period.

2.2 The stroke unit

The SU was representative of a typical Scandinavian-model comprehensive SU (Langhorne & Pollock, 2002) in both 1994 and 2012. It is a dedicated ward with 10 beds in 1994 and 29 beds in 2012. In 2012, four were located in an intensive monitoring area. The catchment area comprised 291,905 persons in 1994 (49,303 aged ≥60 years) and 498,697 in 2012 (96,920 aged ≥60) (Official Statistics of Norway, 2018). The large increase in persons was due to the inclusion of three Oslo boroughs in 2011, which led to an increase of 45% to the catchment area. The current practice guidelines were utilized (Committee for medical technology evaluation at the Norwegian Research Council, 1995; Norwegian Directorate of Health, 2010), and the recommended features of SU care (Stroke Unit Trialists' Collaboration, 2013) were present at both time points. The unit is described in detail elsewhere (Ronning & Guldvog, 1998a, 1998b).

The main difference between 1994 and 2012 was the use of intravenous thrombolysis and endovascular interventions. In 1994, there was no recommendation for thrombolysis outside of clinical trials. In 2012, recanalization treatment (primarily thrombolysis) was considered in patients presenting within 4.5 hr and without contraindications. Thrombectomy, while available in 2012, was performed on only five patients.

Physiological parameters were systematically and intermittently registered; in 2012, continuous monitoring was available on indication. Other differences include improved imaging techniques, including MRI angiography and more use of ultrasound, and the availability of newer oral medications in 2012 versus 1994. Surgery for carotid stenosis was generally performed within 2 weeks of the stroke in 2012 versus 6 months in 1994. Combination antithrombotic therapy or monotherapy with clopidogrel was routinely prescribed in 2012, as were lipid-lowering agents. Patients in the 1994 cohort were quasi-randomized to supplemental oxygen or not for the first 24 hr as part of an additional study; (Ronning & Guldvog, 1999) however, the treating physician was instructed to administer oxygen on indication regardless of randomization.

2.3 Outcomes and measures

The primary outcome in this study was all-cause mortality during the 3 years (1,080 days) following index stroke. Mortality information was obtained via the official national register.

Stroke severity on admission was scored prospectively by the neurologist on duty. In the 1994 cohort, the Scandinavian Stroke Scale (SSS) (Scandinavian Stroke Study Group, 1985) was used, and in 2012 the National Institutes of Health Stroke Scale (NIHSS) (Brott et al., 1989). Both scales are reliable and valid (Askim, Bernhardt, Churilov, & Indredavik, 2016; Goldstein & Samsa, 1997; Lindenstrøm & Boysen, 1991). Where a prospective NIHSS score was unavailable, the first author (ASL) scored patients retrospectively using admission records and a validated algorithm (Williams, Yilmaz, & Lopez-Yunez, 2000). For between-cohort comparability, the scales were trichotomized using previously published, comparable cut-offs (Askim et al., 2016; Bernhardt et al., 2015; Govan, Langhorne, & Weir, 2009) into mild (NIHSS: 0–7; SSS: 43–58), moderate (NIHSS: 8–16; SSS: 26–42), and severe (NIHSS: 17–42; SSS: 0–25). Primary stroke type was determined via imaging (ischemic vs. hemorrhagic). Reduced consciousness at admission was defined by a score of ≤2 on item 1 of the SSS in 1994 and by a Glasgow Coma Scale score of ≤10 in 2012, as these were deemed to be equivalent. Length of stay was recorded.

Patient demographics, medication use and the following comorbidities and stroke risk factors were registered at admission: previous cerebrovascular disease (transient ischemic attack or stroke), myocardial infarction, treated hypertension or diabetes, any cancer diagnosis, and current smoking status. Atrial fibrillation was considered present if previously diagnosed or shown on electrocardiogram during admission.

Level of function poststroke was graded using the Barthel Index (BI) (Mahoney & Barthel, 1965) or modified Rankin Scale (mRS) (Swieten, Koudstaal, Visser, Schouten, & Gijn, 1988). BI was scored in 1994, and either BI or mRS in 2012. The scales are highly correlated (Uyttenboogaart, Luijckx, Vroomen, Stewart, & Keyser, 2007), and patients were classified as being independent by either BI score ≥85 or mRS score ≤2. These cutoffs are shown to be comparable (Sulter, Steen, & Keyser, 1999; Uyttenboogaart et al., 2007) and are commonly used to indicate “good outcome.” Function was scored on day 4 or 5 of admission in 1994, and in 2012 on median day 4 (interquartile range [IQR]: 2–6).

2.4 Statistical analysis

Continuous variables are presented as mean and standard deviation (SD), or median and IQR, and categorical variables as frequency and percentage. Independent samples t tests were used to test differences between continuous outcomes, chi-squared tests for categorical outcomes. Adjusted odds ratios (ORs) were estimated using logistic regression. Survival analysis was performed using Kaplan–Meier survival plots and the log-rank test for between-group differences. Hazard ratios (HRs) were estimated using Cox regression for the entire follow-up time, and in a subanalysis of different time points and intervals poststroke. We allowed a minimum of ten events-per-variable for adjusted HRs. Variables entered into the models were selected based on current knowledge, without using a computerized selection process. We were unable to construct fully adjusted models for ischemic and hemorrhagic stroke separately due to the study's moderate sample size; however, we included a dummy ICH variable in the overall Cox regression model to partially compensate for this while still retaining power, and also constructed smaller adjusted Cox regression models for each stroke type separately, the results of which were not significant. Due to relatively few events at 7 days, we limited adjustments in the subanalysis to the seven variables, including cohort, we deemed most relevant. Assessments for collinearity, missed confounding due to baseline differences, and the proportional hazards assumption were performed and found to be satisfactory. SPSS version 21 was used for all analyses.

2.5 Ethical considerations

Collection of the 1994 cohort data was approved by the Regional Committee for Medical and Health Research Ethics (REC; approval number S-93231), and consent obtained prior to recruitment. The NOR-SPOT project was classified as a quality assurance project by REC so ethical approval was granted by the Data Protection Officer at Akershus University Hospital (approval number 11-076), in accordance with REC's recommendation. Permission for the use of data from 1994 for the current study was deemed by REC to fall outside of its mandate since the data were fully anonymized. Consequently, approval for its use was granted by the hospital's Data Protection Officer under NOR-SPOT's existing approval number.

3.1 Demographics, risk factors and clinical features

Patients in the 2012 cohort were older than in 1994 (mean age 78.8 vs. 76.7 years, p = 0.001), Table 1. Almost half (48.6%) of the patients in 2012 were aged 80 years and above, compared to 32.1% in 1994, Figure 2a. The shift toward higher age strata was most apparent in females, Figure 2b. Similar proportions of included patients were female, married, and living alone; however, more patients were admitted from nursing homes in 2012 (9.9% vs. 2.2%, p < 0.001). Smoking rates were unchanged.

There were significantly more patients in 2012 with atrial fibrillation (33.7% vs. 21.4%, p < 0.001), malignancy (19.2% vs. 8.9%, p < 0.001), and using antiplatelets (46.9% vs. 26.2%, p < 0.001), warfarin (16.3% vs. 5.5%, p < 0.001), and antihypertensives (69.6% vs. 56.1%, p < 0.001) at admission, even after adjusting for age and sex. Patients were still more likely to be taking antiplatelets (OR: 2.90; 2.05–4.11) and warfarin (OR: 2.98; 1.62–5.48) at admission after also adjusting for relevant previous diagnosed illnesses. Rates of hypertensive prescription were no longer significantly different after these adjustments.

A similar proportion of patients were admitted with intracerebral hemorrhage and reduced consciousness; however, stroke severity was significantly milder in 2012, with a general shift toward milder strokes (Figure 3). Length of stay was shorter in 2012: median 6.9 (IQR: 4.2–9.7) versus 8.0 (IQR: 5.0–13.0), p < 0.001.

Data on functional independence on day 4–5 were available for 661 patients. In 2012, 46.4% were classified as independent compared to 35.7% in 1994, p = 0.007; however, this was no longer statistically significant after adjusting for age, sex, stroke severity and type.

3.2 Survival

During the two distinct 3-year observation periods, 125 patients (46.1%) in 1994 and 240 (44.0%) in 2012 died. The crude survival plots (Figure 4) show overall nonsignificant differences in survival. Adjusting for potential confounders did not change this observation; the adjusted HR for 3-year survival in 2012 versus 1994 was 0.99 (95% CI: 0.77–1.28), see Supporting Information Table S1 for full model.

Adjusted HRs for death were estimated for different times following stroke (Table 2). Seven-day case fatality was 8.9% in 1994 and 8.6% in 2012. At 30 days, case fatality was slightly higher in 2012 at 18.9% versus 16.2%, HR 1.68 (1.14–2.47). Similarly, the risk during days 8–30 was slightly higher in 2012, HR 1.78 (1.01–3.13). Adjusted survival was not significantly different between the cohorts beyond 30 days. Stroke severity, stroke type, and age were the most important factors independently related to mortality in the subanalysis (see Supporting Information Table S2). Early case fatality at 7 days was only predicted by stroke severity (HR: 3.59 [1.35–9.55] moderate vs. mild) and type (HR: 3.03 [1.86–4.93] ICH vs. infarct). Age became significant for survival beyond 7 days and was the only significant factor for the interval 1–3 years poststroke (HR: 1.09 [1.07–1.12]).