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Review
. 2020 Feb 24;4(1):e100013.
doi: 10.1136/bmjos-2019-100013. eCollection 2020.

Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

Sarah K McCann  1 , Catherine B Lawrence  2
Affiliations
Review

Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

Sarah K McCann et al. BMJ Open Sci. .

Abstract

Stroke is a significant cause of mortality and morbidity for which there are limited treatment options. Virtually all drug interventions that have been successful preclinically in experimental stroke have failed to translate to an effective treatment in the clinical setting. In this review, we examine one of the factors likely contributing to this lack of translation, the failure of preclinical studies to consider fully the advanced age and comorbidities (eg, hypertension or diabetes) present in most patients with stroke. Age and comorbidities affect the likelihood of suffering a stroke, disease progression and the response to treatment. Analysing data from preclinical systematic reviews of interventions for ischaemic stroke we show that only 11.4% of studies included an aged or comorbid model, with hypertension being the most frequent. The degree of protection (% reduction in infarct volume) varied depending on the comorbidity and the type of intervention. We consider reasons for the lack of attention to comorbid and aged animals in stroke research and discuss the value of testing a potential therapy in models representing a range of comorbidities that affect patients with stroke. These models can help establish any limits to a treatment's efficacy and inform the design of clinical trials in appropriate patient populations.

Keywords: aged; comorbidity; ischaemia; preclinical; stroke.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
The number of included studies published per year. The number of publications reporting outcomes in aged or comorbid animals is shown in black and in non-comorbid animals in white.
Figure 2
Figure 2
Inclusion of advanced age or a comorbidity in preclinical stroke studies testing an intervention. Presented as a percentage of all studies (n=842): n=746 non-comorbid (88.6%), n=68 hypertension (8.1%), n=14 diabetic/hyperglycaemic (1.7%), n=12 aged (1.4%), n=2 infection (0.2%).
Figure 3
Figure 3
Reduction in infarct volume in non-comorbid versus comorbid animals. Less brain protection is observed after stroke and intervention in comorbid (n=163 outcomes) compared with non-comorbid (n=1703 outcomes) animals (p=0.003). Results are presented as the mean±95% CIs. The horizontal grey bar represents the 95% CIs of the combined effect of both comorbid and non-comorbid data.
Figure 4
Figure 4
The impact of comorbidity and intervention type on reduction in infarct volume. The degree of protection observed in aged or comorbid animals varied depending on the type of comorbidity modelled (A; p=0.017) and the type of intervention administered (B; p<0.001). Results are presented as the mean±95% CIs, n=163 outcomes in total. The number of outcomes in each subgroup is shown in brackets. The horizontal grey bars represent the 95% CIs of the combined effect of the comorbid data. HMG-CoA, hydroxymethylglutaryl-coenzyme A; NO, nitric oxide; NOS, nitric oxide synthase; PPAR, peroxisome proliferator-activated receptor.
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