Cognitive impairment and medication adherence post-stroke: A five-year follow-up of the ASPIRE-S cohort

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Abstract

Background

Control of vascular risk factors is essential for secondary stroke prevention. However, adherence to secondary prevention medications is often suboptimal, and may be affected by cognitive impairment. Few studies to date have examined associations between cognitive impairment and medication adherence post-stroke, and none have considered whether adherence to secondary prevention medications might affect subsequent cognitive function. The aim of this study was to explore prospective associations between cognitive impairment and medication non-adherence post-stroke.

Methods

A five-year follow-up of 108 stroke survivors from the Action on Secondary Prevention Interventions and Rehabilitation in Stroke (ASPIRE-S) prospective observational cohort study. Cognitive function was assessed using the Montreal Cognitive Assessment at 6 months, and a neuropsychological test battery at 5 years. Adherence to antihypertensive, antithrombotic and lipid-lowering medications was assessed using prescription refill data.

Results

The prevalence of cognitive impairment at five years was 35.6%. The prevalence of non-adherence ranged from 15.1% for lipid-lowering agents to 30.2% for antithrombotics. There were no statistically significant associations between medication non-adherence in the first year post-stroke and cognitive impairment at 5 years, nor between cognitive impairment at 6 months and non-adherence at 5 years. Stroke survivors with cognitive impairment were significantly more likely to report receiving help with taking medications [OR (95% CI): 4.84 (1.17, 20.07)].

Conclusions

This is the first study to explore the potential impact of non-adherence to secondary prevention medications on cognitive impairment in stroke survivors. Findings highlight the role of family members and caregivers in assisting stroke survivors with medication administration, particularly in the context of deficits in cognitive function. Involving family members and caregivers may be a legitimate and cost-effective strategy to improve medication adherence in stroke survivors.

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Most cited references 42

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Medication adherence: its importance in cardiovascular outcomes.

P Michael Ho, Chris L Bryson, John S Rumsfeld (2009)

Medication adherence usually refers to whether patients take their medications as prescribed (eg, twice daily), as well as whether they continue to take a prescribed medication. Medication nonadherence is a growing concern to clinicians, healthcare systems, and other stakeholders (eg, payers) because of mounting evidence that it is prevalent and associated with adverse outcomes and higher costs of care. To date, measurement of patient medication adherence and use of interventions to improve adherence are rare in routine clinical practice. The goals of the present report are to address (1) different methods of measuring adherence, (2) the prevalence of medication nonadherence, (3) the association between nonadherence and outcomes, (4) the reasons for nonadherence, and finally, (5) interventions to improve medication adherence.

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Classification and natural history of clinically identifiable subtypes of cerebral infarction.

J. Bamford, P Sandercock, M. Dennis … (1991)

We describe the incidence and natural history of four clinically identifiable subgroups of cerebral infarction in a community-based study of 675 patients with first-ever stroke. Of 543 patients with a cerebral infarct, 92 (17%) had large anterior circulation infarcts with both cortical and subcortical involvement (total anterior circulation infarcts, TACI); 185 (34%) had more restricted and predominantly cortical infarcts (partial anterior circulation infarcts, PACI); 129 (24%) had infarcts clearly associated with the vertebrobasilar arterial territory (posterior circulation infarcts, POCI); and 137 (25%) had infarcts confined to the territory of the deep perforating arteries (lacunar infarcts, LACI). There were striking differences in natural history between the groups. The TACI group had a negligible chance of good functional outcome and mortality was high. More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infarct. Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups. Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome. Despite the small anatomical size of the infarcts in the LACI group, many patients remained substantially handicapped. The findings have important implications for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups.

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European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

H.C. Diener, L. Cunha, C. Forbes … (1996)

In 1988, we undertook a randomized, placebo-controlled, double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid (ASA), modified-release dipyridamole, and the two agents in combination for secondary prevention of ischemic stroke. Patients with prior stroke or transient ischemic attack (TIA) were randomized to treatment with ASA alone (50 mg daily), modified-release dipyridamole alone (400 mg daily), the two agents in a combined formulation, or placebo. Primary endpoints were stroke, death, and stroke or death together. TIA and other vascular events were secondary endpoints. Patients were followed on treatment for two years. Data from 6,602 patients were analysed. Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke (p < or = 0.001) and stroke or death combined (p < 0.01). In pairwise comparisons, stroke risk in comparison to placebo was reduced by 18% with ASA alone (p = 0.013); 16% with dipyridamole alone (p = 0.039); and 37% with combination therapy (p < 0.001). Risk of stroke or death was reduced by 13% with ASA alone (p = 0.016); 15% with dipyridamole alone (p = 0.015); and 24% with the combination (p < 0.001). The treatment had no statistically significant effect on the death rate alone. Factorial analysis also demonstrated a highly significant effect of ASA (p < 0.001) and dipyridamole (p < 0.01) for preventing TIA. The risk reduction for the combination was 36% (p < 0.001) in comparison with placebo. Headache was the most common adverse event, occurring more frequently in dipyridamole-treated patients. All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole. We conclude that (1) ASA 25 mg twice daily and dipyridamole, in a modified-release form, at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA; (2) when co-prescribed the protective effects are additive, the combination being significantly more effective than either agent prescribed singly; (3) low-dose ASA does not eliminate the propensity for induced bleeding.

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Author and article information

Contributors

Daniela Rohde:

ORCID: http://orcid.org/0000-0001-8834-2539

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing

Eva Gaynor: Role: Data curationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: Writing – review & editing

Margaret Large: Role: InvestigationRole: Project administrationRole: Writing – review & editing

Lisa Mellon: Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing

Kathleen Bennett: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing

David J. Williams: Role: ConceptualizationRole: ResourcesRole: SupervisionRole: Writing – review & editing

Linda Brewer: Role: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing

Patricia Hall: Role: Data curationRole: InvestigationRole: Project administrationRole: Writing – review & editing

Elizabeth Callaly: Role: Project administrationRole: ResourcesRole: Writing – review & editing

Eamon Dolan: Role: InvestigationRole: Project administrationRole: ResourcesRole: Writing – review & editing

Anne Hickey: Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing

Anthony Pak-Hin Kong: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 17 October 2019

Publication date Collection: 2019

Volume: 14

Issue: 10

Electronic Location Identifier: e0223997

Affiliations

[1 ] Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland

[2 ] Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland

[3 ] Clinical Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland

[4 ] Geriatric and Stroke Medicine, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland

[5 ] Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, Ireland

[6 ] Geriatric Medicine, Connolly Hospital, Dublin, Ireland

University of Central Florida, UNITED STATES

Author notes

Competing Interests: DW has served in the past as an advisory board member for Boehringer Ingelheim, Daiichi Sankyo, Bristol Myers Squibb, and Bayer, and has received personal fees for this outside the submitted work. DW received a speaker honorarium for Boehringer Ingelheim and has received personal fees for this outside the submitted work. All other authors report no conflicting interests. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

* E-mail: danielamrohde@ 123456rcsi.ie

Author information

Daniela Rohde http://orcid.org/0000-0001-8834-2539

Article

Publisher ID: PONE-D-19-15566

DOI: 10.1371/journal.pone.0223997

PMC ID: 6797135

PubMed ID: 31622438

SO-VID: 783a94bf-6451-4fb6-af9e-920c0dab38b1

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 1 June 2019

Date accepted : 2 October 2019

Page count

Figures: 1, Tables: 5, Pages: 15

Funding

Funded by: Health Research Board

Award ID: SPHeRE2013/1

Funded by: Health Research Board

Award ID: 1404/7400

Funded by: Health Research Board

Award ID: RL-15-1579

Award Recipient : Kathleen Bennett

Funded by: funder-id http://dx.doi.org/10.13039/501100001594, Irish Heart Foundation;

Award ID: 1296829

Award Recipient : Eva Gaynor

This work was supported by the Health Research Board ( www.hrb.ie) [grant numbers SPHeRE2013/1, 1404/7400, and RL-15-1579 (to KB)], and the Irish Heart Foundation ( www.irishheart.ie) [grant number 1296829 toEG]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability Data are available upon request. Data are not publicly available due to ethical restrictions, as they contain potentially identifying and sensitive patient information. Ethical approval for this study, and patient informed consent, was provided on the basis that data would not be shared publicly. Data access requests may be sent to the study principal investigators Prof David Williams ( david.williams@ 123456rcsi.ie ) and Prof Anne Hickey ( ahickey@ 123456rcsi.ie ) and the Research Ethics Committee at the Royal College of Surgeons in Ireland ( recadmin@ 123456rcsi.ie ), for researchers who meet the criteria for access to confidential data.

Cognitive impairment and medication adherence post-stroke: A five-year follow-up of the ASPIRE-S cohort

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Abstract

Background

Methods

Results

Conclusions

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Stroke MRI

Most cited references 42

Medication adherence: its importance in cardiovascular outcomes.

Classification and natural history of clinically identifiable subtypes of cerebral infarction.

European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.

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