Age Gap between Stroke Patients Included in Randomized Clinical Trials of Acute Revascularization Therapy and Those in Population-Based Studies: A Review

Abstract

Background: The ongoing aging population in high-income countries is responsible for a dramatic rise in the number of elderly stroke patients in whom many questions remain regarding the use of acute revascularization therapy. This review aimed to compare stroke patients from population-based studies to those included in RCTs in terms of age. Summary: Population-based incidence studies conducted in high income that complied with the defined quality criteria were reviewed (period 1985–2020). RCTs of acute ischemic stroke therapy including intravenous thrombolysis (IVT) with either alteplase or tenecteplase and mechanical thrombectomy (MT) were retrieved from systematic reviews performed in recent guidelines from the European Stroke Organisation. When available, information on either mean and/or median age was extracted from each selected article. As a result, 36 population-based registries were included, 34 of which recorded patients with first-ever stroke over 63 distinct time periods with a total of 38,188 patients. Twenty-nine RCTs enrolling 11,666 patients were identified including 13 RCTs related to IVT with alteplase, 11 RCTs about MT, and 5 RCTs on IVT with tenecteplase. A gap in age between stroke patients in the RCTs and those in population-based studies was observed. With few exceptions, mean age of patients in the RCTs was about 4 years younger than in population-based studies, while the median age was approximately 7 years younger. Thirty-five (83%) population-based incidence studies and 8 RCTs (32%) reported a mean age of patients >70 years old. Mean age ≥75 years was observed in 9 (21%) population-based studies and in only 1 (4%) RCT. All population-based studies and half of the RCTs reported a median age >70 years. Key Messages: The gap in age between patients enrolled in acute stroke therapy RCTs and those from population-based studies highlights an under-representation of elderly stroke patients in RCTs. With the current aging of the population, this trend is likely to increase in the coming years, and there is a need to promote the inclusion of older patients, particularly those with disabilities, in future trials to reflect the true population of stroke patients and to help clinicians have evidence-based data to guide their decision-making.