Interventions for Behaviour Change and Self-Management of Risk in Stroke Secondary Prevention: An Overview of Reviews.

INTRODUCTION: Optimised secondary prevention strategies that include lifestyle change are recommended after stroke. While multiple systematic reviews (SRs) address behaviour change interventions, intervention definitions, and associated outcomes differ between reviews. This overview of reviews addresses the pressing need to synthesise high-level evidence for lifestyle-based behavioural and/or self-management interventions to reduce risk in stroke secondary prevention in a structured, consistent way. METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were applied to meta-analyses, demonstrating statistically significant effect sizes to establish the certainty of existing evidence. Electronic databases MEDLINE, Embase, Epistemonikos, and the Cochrane Library of Systematic Reviews were systematically searched, current to March 2023. RESULTS: Fifteen SRs were identified following screening, with moderate overlap of primary studies demonstrated (5.84% degree of corrected covered area). Interventions identified could be broadly categorised as multimodal; behavioural change; self-management; psychological talk therapies, albeit with overlap between some theoretical domains. Seventy-two meta-analyses addressing twenty-one preventive outcomes of interest were reported. Best-evidence synthesis identifies that for primary outcomes of mortality and future cardiovascular events post-stroke, moderate certainty GRADE evidence supports multimodal interventions to reduce cardiac events, with no available evidence for outcomes of mortality (all-cause or cardiovascular) or recurrent stroke events. For secondary outcomes addressing risk-reducing behaviours, best-evidence synthesis identifies moderate certainty GRADE evidence for multimodal lifestyle-based interventions to increase physical activity participation, and low certainty GRADE evidence for behavioural change interventions to improve healthy eating post-stroke. Similarly, low certainty GRADE evidence supports self-management interventions to improve preventive medication adherence. For mood self-management post-stroke, moderate GRADE evidence supports psychological therapies for remission and/or reduction of depression and low/very low certainty GRADE evidence for reduction of psychological distress and anxiety. Best-evidence for outcomes addressing proxy physiological measures identified low GRADE evidence supporting multimodal interventions to improve blood pressure, waist circumference, and LDL cholesterol. CONCLUSION: Effective strategies to redress risk-related health behaviours are required in stroke survivors to complement current pharmacological secondary prevention. Inclusion of multimodal interventions and psychological talk therapies in evidence-based stroke secondary prevention programmes is warranted given the moderate GRADE of evidence that supports their role in risk reduction. Given the overlap in primary studies across reviews, often with overlapping theoretical domains between broad intervention categories, further research is required to identify optimal intervention behavioural change theories and techniques employed in behavioural/self-management interventions.

Long-term outcome of a pragmatic trial of multifaceted intervention (STROKE-CARD care) to reduce cardiovascular risk and improve quality-of-life after ischaemic stroke and transient ischaemic attack: study protocol.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted. METHODS: We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3-6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management. DISCUSSION: This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

A pilot study of the ticagrelor role in ischemic stroke secondary prevention.

INTRODUCTION: Ticagrelor is one of the most recent antiplatelet drugs used to treat ischemic heart disease. Its efficacy may equal or exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA. AIM OF THE WORK: We aimed at evaluating the safety (as a primary endpoint) and efficacy (as a secondary endpoint) of a 180 mg loading dose of ticagrelor given within 9 h from the onset of first-ever ischemic stroke. METHODS: We conducted an open-label, randomized prospective controlled clinical trial between May 2019 and September 2020 on patients who presented with their first-ever ischemic stroke and were recruited from the emergency department, of Kafr el-sheik University Hospitals, Egypt. Eligible patients randomly received aspirin or ticagrelor loading and maintenance doses. Treatment began within 9 h of stroke onset. RESULTS: Aspirin was given to 84 patients; ticagrelor was given to 85. There was no significant difference between the 2 groups regarding the hemorrhagic and nonhemorrhagic complications. Patients who received ticagrelor had a better outcome regarding NIHSS improvement at 2 days and 1 week or discharge and a favorable mRS score after 1 week or discharge and at 90-day follow-up. CONCLUSION: Ticagrelor was noninferior to aspirin regarding safety profile. Compared with aspirin, ticagrelor had a better clinical outcome based on NIHSS and mRS in first-ever acute ischemic stroke patients who received it within 9 h from symptom onset, leading to a shorter hospital stay.

Treatments in Ischemic Stroke: Current and Future.

BACKGROUND AND AIM: Despite progress made over the last 30 years, stroke is still a leading cause of disability and mortality; likewise, its burden is expected to increase over the next decades, due to population growth and aging. The development of drugs with better safety-efficacy profiles as well as strategies able to improve ischemic stroke management from the pre-hospital setting is needed. SUMMARY: The pathophysiology of ischemic stroke involves multiple pathways resulting in cerebral artery obstruction and brain tissue ischemia. To date, the only approved drug for acute ischemic stroke is intravenous thrombolytic alteplase. Intravenous thrombolysis (IVT) can be administered alone or in combination with endovascular treatment (EVT) with mechanical thrombectomy, in case of large vessel occlusion and generally within 6 h from symptoms onset. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the reasons for the reluctance to administer IVT. Tenecteplase is a promising alternative fibrinolytic agent, having a better safety profile than alteplase. Moreover, recent evidences have allowed an extension of the IVT ± EVT time window for patients with unknown onset time and for those with a known onset time thanks to the new "tissue-window" approach guided by advanced neuroimaging techniques, which also helps in collateral circulation estimation. Regarding primary-secondary prevention, researchers are focused on improving the efficacy of antithrombotic drugs with a "hemostasis-sparing" approach. Neuroprotective agents are also under development, particularly stem cells. The COVID-19 pandemic has critically stressed global healthcare systems, with collateral damage resulting in access delivery of only emergency care, such as ischemic stroke. Regarding telemedicine, it has had a minor role in acute stroke management, and with the onset of COVID-19, this role will most likely be adopted to increase access and delivery in stroke assessment, but also in the follow-up.

Closure versus Medical Therapy for Patent Foramen Ovale in Patients with Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Debate continues about whether percutaneous closure of patent foramen ovale (PFO) is a better strategy for the treatment of patients with cryptogenic stroke in comparison with medical therapy alone. We performed an updated meta-analysis of 6 randomized controlled trials (RCTs) to assess the effectiveness and safety of percutaneous closure of PFO as secondary prevention for patients with previous cryptogenic stroke compared to medical therapy. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and Internet-based resources were retrieved in March 2018 for eligible RCTs. The primary effectiveness outcome was recurrent strokes. RESULTS: Six studies meeting our selection criteria were identified. Among 3560 participants, 1889 patients were assigned to PFO closure and 1671 patients to medical therapy. There were no significant differences among the baseline characteristics. The pooled incidence of recurrent strokes was 1.96% in the PFO closure group and 4.60% in the medical therapy group (Relative risk [RR] .39, 95% confidence interval [CI] .18-.82, P = .01). Newly detected atrial fibrillation occurred in 77 of 1844 (4.18%) patients in the PFO closure group and in 12 of 1667 (.72%) patients in the medical therapy group (RR 4.56, 95% CI 2.21-9.41, P <.0001). There was no difference in terms of serious adverse events, total mortality or bleeding between 2 groups. CONCLUSIONS: Our updated meta-analysis suggests that in patients with PFO and cryptogenic stroke, the rate of recurrent stroke is significantly reduced with percutaneous closure of PFO compared to the medical therapy.

Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke: A propensity-matched analysis of a global federated health database.

INTRODUCTION: Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS. PATIENTS AND METHODS: This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI). RESULTS: Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups. DISCUSSION AND CONCLUSION: Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.

Association between the Suita Score and Stroke Recurrence in Patients with First-ever Ischemic Stroke: A Prospective Cohort Study.

Objective The Suita score is used to predict the 10-year prognosis of developing coronary heart disease (CHD). This study examined the association between the Suita score and stroke recurrence within one year in Japanese patients who experienced first-ever ischemic stroke. Methods This prospective cohort study at a stroke center in Japan included patients who experienced first-ever acute ischemic stroke (AIS) or a transient ischemic attack (TIA). During hospitalization, the Suita score was measured as the main exposure. Patients with a ≥5% predicted CHD risk were classified into the high-risk group. The primary outcome was stroke recurrence within one year of the stroke onset. A multivariate Cox regression analysis was conducted and adjusted for confounding and prognostic factors. Results Among the 1,204 patients evaluated, 937 (78%) were classified as having a high risk of developing CHD. Stroke recurrence was observed in 66 patients during the follow-up period. In the multivariate analysis, after adjusting for confounding and prognostic factors, such as non-small vessel occlusion and prescription of lipid-lowering agents at the time of discharge, a ≥5% predicted CHD risk was associated with the 1-year stroke recurrence after the initial onset [adjusted hazard ratio (HR) =2.20, 95% confidence interval (CI) =1.00-4.91, p=0.049; adjusted HR=2.00, 95% CI=1.01-4.14, p=0.048; adjusted HR=0.42, 95% CI=0.24-0.73, p=0.002]. Conclusion The Suita score, adapted for use in ischemic stroke with the same mechanism, correlated with the short-term recurrence within one year. Our findings suggest that the Suita score may be useful for predicting the long-term prognosis of developing CHD as well as the short-term recurrence for patients with first-ever AIS and TIA.

Cardiovascular medications and long-term mortality among stroke survivors in the Brazilian Study of Stroke Mortality and Morbidity (EMMA).

AIM: To investigate the association between medication use and long-term all-cause mortality in a Brazilian stroke cohort. METHODS: Both ischemic and hemorrhagic stroke were evaluated. Medication use was assessed as: never, only pre-stroke, only post-stroke, and continuous use. We evaluated anti-hypertensives, anti-diabetics, lipid-lowering drugs, anti-platelets, and anti-coagulants. Cox regression models were adjusted for sociodemographic and cardiovascular risk factors. RESULTS: Among 1173 incident stroke cases (median age: 68; 86.8% were ischemic, 70% first-ever stroke), medication use was low (overall: 17.5% pre-stroke, 26.4% post-stroke, and 40% were under continuous use). Anti-hypertensives and anti-platelets (aspirin) were the continuous cardiovascular medications used most often, at 83.5% and 72%, respectively, while statins (39.7%) and anti-diabetics (31.3%) were the least used. Medication use (pre-stroke, post-stroke and continuous use) was associated with a reduction in all-cause mortality risk, particularly among those under continuous use (multivariable hazard ratio, 0.52; 95% confidence interval (CI), 0.46-0.66) compared with never-users. Among ischemic stroke patients, this effect was similar (multivariable hazard ratio, 0.52; 95% CI, 0.40-0.68). No significant associations were evident among hemorrhagic stroke patients. CONCLUSIONS: The risk of all-cause mortality was reduced by 48% among those with ischemic stroke under continuous use of medications. Secondary prevention should be emphasized more strongly in clinical practice. Geriatr Gerontol Int 2022; 22: 715-722.

A new model for secondary prevention of stroke: transition coaching for stroke.

Non-adherence to stroke prevention medications is a risk factor for first-ever and recurrent stroke. As of yet, there are no guidelines for processes to recognize and address medication non-adherence in stroke patients. We developed a new model of post-discharge prevention care that measures and addresses medication-taking (transition coaching for stroke or TRACS). TRACS includes personalized education about risk factors and medications prior to discharge, follow-up telephone calls, and appointments with a stroke nurse practitioner (NP). The stroke NP asks about medication use (persistence) and whether doses are missed (adherence), and helps to solve problems with access to medications or side effects. In an analysis of 142 patients enrolled in TRACS from October 2012 to February 2014, medication persistence (use of medications from discharge to the time of measurement) was about 80%. Medication persistence at NP visit was higher in those patients with a first-ever stroke (78.9%) vs. those with recurrent stroke (60.7%; p = 0.045). Concerted efforts with 2-day RN follow-up calls and earlier NP appointments to improve medication-taking behaviors are underway.