Inclusion of very elderly in clinical stroke trials is essential and feasible

Sanossian N, Apibunyopas KC, Liebeskind DS, et al.
Stroke, 2016;47:00-00. DOI: 10.1161/STROKEAHA.116.013318

Background

The population very elderly (≥80 years) is one of the most rapidly growing age groups. With improving life expectancy, the extreme elderly population (≥90 years) is also expected to continue to grow exponentially. These people are at an increased risk for stroke, have the highest risk for complications from stroke treatments and are at a significantly higher risk of mortality secondary to stroke [1].

However, acute stroke trials frequently exclude elderly from the study and therefore limited information is known about the therapeutic efficacy in these patients. It is therefore important not to exclude the very and extreme elderly in future studies, but we are not certain how their inclusion would affect acute stroke trials.

To explore this, this study described the characteristics of the very elderly (80-95 years) that were enrolled in a multicentre prehospital acute stroke treatment phase III trial, the FAST-MAG study (Field Administration of stroke therapy-magnesium). In this trial, suspected hyperacute stroke patients within the first 2 hours of last known well time, received either magnesium sulphate or placebo.  

Main results

• 490 individuals were ≥80 yrs (elderly), with 60 individuals being ≥90 yrs (extreme elderly). 1210 Patients were non-elderly.   
• Demographics: compared to non-elderly, very elderly were more often white (87% vs. 74%, P<0.01) and more likely to be women (53% vs. 38%, P<0.01). This was comparable with the extreme elderly (88% white, P=0.123 and 68% women, P<0.01). Moreover, very- and extreme elderly were less likely to be of Hispanic ethnicity (15% and 12% respectively) compared to non-elderly (27%, P<0.01 and P=0.026 respectively).
• Stroke: ischemic stroke was more common in the very elderly group (82% vs. 70% in the non-elderly, P<0.01) and intracerebral hemorrhage was less common (14.5% vs. 26.1% in the non-elderly).
• Comorbidities: compared to non-elderly, very elderly more often had hypertension (85% vs. 75%, P<0.01), hyperlipidaemia (52% vs. 45%, P<0.01), atrial fibrillation (AF, 38% vs. 15%, P<0.01) and coronary artery disease (28% vs. 18%, P<0.01). In contrast, the prevalence of diabetes mellitus was lower in the very elderly (19% vs. 24%, P=0.024). Comparing extreme elderly to non-elderly and very elderly, a history of AF (35% vs. 21.2%, P=0.01) and AF on ECG (28% vs. 18%, P=0.038) were more frequently observed.
• Behavioural risk factors (eg. alcohol and tobacco use) were less common in elderly; only 4% of the very elderly and none of the extreme elderly used tobacco as opposed to 23% of the non-elderly (P<0.01).
• Treatment: no difference between the proportion of individuals who received reperfusion therapies.
• Outcome (modified Rankin Scale): Very elderly individuals had higher scores when compared to non-elderly (non-elderly, very, extreme elderly score 3-6: 42.8%, 59.9%, 74.1% respectively, score 4-6: 31.5%, 46.3%, 53.4% and score 5-6: 21.8%, 34.9%, 44.8%, all P<0.01). However, there were significant numbers of very elderly (40%) and extreme elderly (25%) that were functionally independent at 90 days post stroke.

Conclusion

Enrolment of very elderly and extreme elderly individuals in clinical stroke research is feasible and desirable. This is important because there are significant demographic, comorbidity and outcome differences between elderly and non-elderly.

Editorial comment [2]

In this editorial, Richard Lindley explains that randomized controlled trials for stroke commonly use upper age limits because of historical precedent, risk management by pharmaceutical companies, fears of unacceptable side effects and practical issues of consent, recruitment and follow-up. He notes that the results of the study done by Sanossian  and coworkers “are important and illustrate some important aspects of modern stroke care”. He highlights the large, but epidemiologically matching, population of elderly with the disease in question, whom can thus not continuingly being excluded. Moreover he emphasizes that there were some important baseline characteristics that illustrate the difference between older and younger people. “In general, treatment effects rarely change direction with age, that is, a beneficial treatment at younger age is usually beneficial at older age but with some provisos.” But stroke is not a homogeneous population as with other diseases. “Baseline characteristics of the older FAST-MAG participant reveals striking differences in atrial fibrillation, which will inevitably lead to different stroke subtypes.” According to Lindley, the other big issue is frailty. Measures of frailty have been developed and trialists have started to measure frailty as baseline, which should become routine.  

Find this article online at Stroke

References

1. Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC, et al; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention
of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42:227–276. doi: 10.1161/STR.0b013e3181f7d043.
2. Lindley RI, Inclusion of Older People in Trials Lessons From FAST-MAG (Field Administration of Stroke Therapy-Magnesium), Stroke, Published Ahead of Print: September 27, 2016