Discussion
multimorbidity, stroke, ICH, TIA/stroke, dementia, ischemic stroke, Multimorbidity, atrial fibrillation, poststroke, aphasia, premorbid disability
STROKE, MINOR, ISCHEMIC STROKE, ATRIAL FIBRILLATION, EVENTS
Multimorbidity has been widely reported to be associated with an increased short-term and medium-term mortality after stroke, which might provide some justification for exclusion of patients from randomized controlled trials of certain interventions. However, although some previous studies of the association of multimorbidity with outcome after stroke adjusted for stroke severity, none of the 22 studies included in recent reviews looked specifically at the association between multimorbidity and early stroke severity, and none stratified analyses by etiologic subtype of ischemic stroke.One previous study reported analyses of the prognostic value of multimorbidity in ischemic stroke vs ICH,Our findings have implications for stroke researchers, clinicians, and policymakers. First, our results underscore the importance of adjusting for premorbid disability and stratifying by etiologic subtype in future research studies of multimorbidity and stroke. Second, given the aging population and predicted rises in rates of multimorbidity, our data suggest that the overall cost and burden of stroke will rise in parallel due to the association with stroke subtypes that tend to be more severe even though multimorbidity seems not be associated with a greater severity of stroke within individual subtypes. Third, this lack of a subtype-specific association of multimorbidity with stroke severity, and the weak association with early mortality after adjustment for confounders, suggests that the presence of multimorbidity per se should not discourage active treatment in routine clinical practice. Previous studies of the association of multimorbidity and poststroke mortality have focused mainly on longer-term mortality, and reports of increased early mortality may have overestimated the association by use of administrative data alone, without the potential to stratify by stroke subtype.Our findings also have implications for the design, performance, and interpretation of trials in patients with stroke. First, our finding that more than a quarter of stroke patients has multiple prior comorbidities highlights the importance of being able to apply trial evidence in clinical decision-making in this group. Second, our finding that multimorbidity was not independently related to stroke severity, and was only weakly associated with short-term mortality, suggests patients with multimorbidity should not be routinely excluded from trials unless there is a specific reason to do so. Third, our finding that approximately half of stroke patients with multimorbidity have an mRS ≥2 highlights 1 important mechanism for exclusion from trials and supports the use of primary outcomes based on ordinal rather than dichotomous analysis of the mRS.Our study did, however, have several limitations. First, there is a risk of ascertainment bias whereby patients with multimorbidity may be less likely to present after minor stroke or clinicians may attribute symptoms of minor events to existing comorbidities. However, our case ascertainment aimed to identify all patients who sought medical attention with TIA/stroke symptoms irrespective of the presumptive diagnosis of the clinician who first assessed them. Moreover, residual underascertainment of patients with minor events would have increased the apparent association of multimorbidity with stroke severity. We also attempted to minimize any potential bias in relation to delayed presentation or delayed initial clinical assessment in patients with multimorbidity by assessing the NIHSS at a uniform time point after stroke onset (usually approximately 24 hours). Second, it is possible there was some underascertainment of comorbidities, particularly in patients with aphasia or dementia. However, we also obtained recorded prior comorbidities from all hospital and primary care medical records. Third, our analyses stratified by etiologic subtype of ischemic stroke were underpowered to exclude weak associations with outcome within subtypes. Fourth, potential withdrawal/withholding of care or advanced directives in patients with multimorbidity might bias associations with outcome. However, although we did not collect data on withdrawal/withholding of care or on advanced directives, exclusion of patients most likely to have treatment withheld did not alter our findings. Similarly, we did not measure the intensity of care in stroke patients with multimorbidity, which should be explored in future studies, but sensitivity analyses in relation to receipt of thrombolysis or thrombectomy did not alter our findings. Fifth, our findings should be interpreted in light of the fact that our study population is predominantly Caucasian. Finally, the CCI does not include all comorbidities that might be associated with the severity of stroke. For example, we showed that prior atrial fibrillation was strongly predictive of increased severity. However, excluding patients with prior atrial fibrillation did not alter our findings.In conclusion, multimorbidity was common in patients with stroke and was associated with premorbid disability, but it was not associated with increased severity of stroke independent of etiologic subtype, or with an increased proportion of ICH, and was only modestly associated with 90-day mortality after adjustment for premorbid disability and stroke severity.