Dataset Information

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

ABSTRACT:

Introduction

Branch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent stroke in acute small subcortical infarction caused by BAD.

Methods and analysis

In this prospective, single-centre, open-label, non-randomised, single-arm study using a historical control, we will compare early DAPT and high-intensity statin treatment with a historical control group of patients with BAD who were treated with single antiplatelet therapy without high-intensity statin treatment. Patients will be eligible for enrolment if they are admitted for acute ischaemic stroke within 24 hours, have a National Institutes of Health Stroke Scale (NIHSS) score of 1-8 and are diagnosed with BAD by MRI. Patients will take aspirin, clopidogrel and high-intensity statins (atorvastatin or rosuvastatin) within 24 hours of stroke onset, followed by aspirin or clopidogrel alone from day 22. The primary endpoint is the percentage of patients who develop END within 7 days of stroke onset (defined as an increase in the NIHSS score ≥2 points) and recurrent stroke within 30 days. The total sample sizes will be 138 for the intervention group and 277 for the control group. A historical control group will be drawn from previous prospective observation studies.

Ethics and dissemination

The protocol of this study has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (202001386A3). All participants will have to sign and date an informed consent form. The findings arising from this study will be disseminated in peer-reviewed journals and academic conferences.

Trial registration number

NCT04824911.

SUBMITTER: Huang YC

PROVIDER: S-EPMC8628334 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

Huang Yen-Chu YC Lee Jiann-Der JD Weng Hsu-Huei HH Lin Leng-Chieh LC Tsai Yuan-Hsiung YH Yang Jen-Tsung JT

BMJ open 20211126 11

<h4>Introduction</h4>Branch atheromatous disease (BAD) contributes to small-vessel occlusion in cases of occlusion or stenosis of large calibre penetrating arteries, and it is associated with a higher possibility of early neurological deterioration (END) and recurrent stroke in acute ischaemic stroke. As the pathology of BAD is due to atherosclerosis, we postulate that early intensive medical treatment with dual antiplatelet therapy (DAPT) and high-intensity statins may prevent END and recurrent ...[more]

PMID: 34836908

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Project description:BackgroundBranch atheromatous disease (BAD) is a primary cause of early neurological deterioration (END) in penetrating artery occlusion, leading to poor functional outcomes. While it has been proposed to classify BAD under large artery atherosclerosis, uncertainty exists regarding the optimal treatment strategy, including cholesterol-lowering targets.ObjectivesWe aimed to assess the clinical implications and temporal changes of atherosclerotic plaques before and after high-intensity statin treatment.DesignThis is a high-resolution vessel-wall imaging sub-analysis of the trial of Statin and Dual Antiplatelet Therapy in Preventing Early Neurological Deterioration in Branch Atheromatous Disease (SATBRAD).MethodsIn this prospective, single-group cohort study, participants in the treatment arm of the SATBRAD trial received early dual antiplatelet therapy and high-intensity statin treatment. The majority of these participants subsequently underwent high-resolution vessel-wall magnetic resonance imaging (MRI). Those with atheromatous plaques in the parent artery continued high-intensity statin treatment for 6 months, followed by a repeat MRI to monitor plaque changes.ResultsThere were 57 patients who underwent vessel-wall imaging and 24 exhibited contrast-enhanced plaques. Patients with contrast-enhanced plaques showed higher rates of END (29.2% vs 6.1%, p = 0.027), perfusion defects (62.5% vs 24.2%, p = 0.004), and lower rates of good outcomes at 3 months (50.0% vs 81.8%, p = 0.011). After adjusting for confounding factors, contrast-enhanced plaque had a negative impact on achieving a good outcome at 3 months (adjusted odds ratio = 0.04; 95% confidence interval = <0.01-0.60). Following high-intensity statin treatment in 36 patients, there was a notable reduction in stenosis (33.7% vs 29.3%, p = 0.005) and contrast-enhanced plaque volume (16.3 vs 11.6 mm3, p = 0.015).ConclusionThe study highlighted the association between contrast-enhanced atherosclerotic plaques, END, and poor functional outcomes, with high-intensity treatment leading to plaque volume reduction. These results underscore the shared pathology between BAD and intracranial atherosclerosis, emphasizing the necessity for further research and tailored treatment strategies for BAD.Trial registrationClinicalTrials.gov; Identifier: NCT04824911 (https://clinicaltrials.gov/study/NCT04824911).

Project description:Background and Objective: Branch atheromatous disease (BAD) is distinctive from large-artery atherosclerosis and small-vessel disease, which is single subcortical infarction caused by the occlusion of perforator's orifice. This study aimed to indicate whether intravenous thrombolysis (IVT) with alteplase could prevent early neurological deterioration (END) and improve functional outcome for patients with BAD within 4.5 h after symptom onset. Methods: We retrospectively analyzed data collected from patients with BAD who were admitted to our hospital from January 2015 to August 2019. To investigate the efficacy and safety of IVT, subjects were classified into alteplase and control groups. A propensity score matching analysis was performed to control substantial heterogeneity of subgroup. The coprimary outcomes were END that is defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days after stroke, and favorable outcome at 3 months after stroke that defined by a score of 0-1 point on the modified Rankin scale (mRS). Results: A total of 135 patients were eventually enrolled in this study (n = 51 for the alteplase group and n = 84 for the control group). Additionally, 42 pairs of subjects were successfully matched by propensity score matching. Intravenous alteplase within 4.5 h after stroke onset reduced the incidence of END [unadjusted odds ratio (OR), 3.32; 95% confidence interval (CI), 1.06-10.37] and improved the clinical outcome at 3 months after stroke, with more patients achieving favorable functional prognosis (mRS, 0-1 point; unadjusted OR, 0.25; 95% CI, 0.10-0.62). Patients in the alteplase group were more likely to be independent (mRS, 0-2 points) at 3 months after stroke (unadjusted OR, 0.33; 95% CI, 0.12-0.90). The rate of death or dependence (mRS, ≥4 points) in the alteplase group was also markedly lower than that in the control group (unadjusted OR, 4.06; 95% CI, 1.03-16.02). Conclusion: Our findings indicated that intravenous thrombolysis may be a safe and effective therapy for patients with BAD.

Project description:BackgroundEarly neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke.MethodsThis study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile.ResultsAmong the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06-5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19-12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups.ConclusionsAs a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban.

Project description:Background and objectivesLong-term treatment with the combination of cilostazol with aspirin or clopidogrel showed a lower risk of stroke recurrence compared to aspirin or clopidogrel alone after high-risk noncardioembolic ischemic stroke in a randomized trial. We aimed to determine whether the effect of the dual medication compared to monotherapy on risk of recurrent ischemic stroke differs according to timing of starting medication after stroke onset.MethodsIn a subanalysis of the randomized controlled trial, patients between 8 and 180 days after stroke onset were randomly assigned to receive aspirin or clopidogrel alone or a combination of cilostazol with aspirin or clopidogrel. They were divided into 3 groups according to the timing of starting trial treatment: between 8 and 14 days after stroke onset (8-14 days group), between 15 and 28 days after stroke onset (15-28 days group), and between 29 and 180 days after stroke onset (29-180 days group). The primary efficacy outcome was the first recurrence of ischemic stroke. Safety outcomes included severe or life-threatening bleeding.ResultsOf 1,879 patients, 498 belonged to the 8-14 days group, 467 to the 15-28 days group, and 914 to the 29-180 days group. There was a significant treatment-by-subgroup interaction for the recurrence of ischemic stroke between trial treatment and trichotomized groups. The recurrence of ischemic stroke was less common with dual therapy than with monotherapy in the 15-28 days group (annualized rate 1.5% vs 4.9%, respectively; adjusted hazard ratio 0.34 [95% CI 0.12-0.95]) and the 29-180 days group (1.9% vs 4.4%, respectively; 0.27 [0.12-0.63]) and similarly common in the 8-14 days group (4.5% for both; 1.02 [0.51-2.04]). Severe or life-threatening bleeding occurred similarly between patients on dual therapy and those on monotherapy in any of the trichotomized groups (crude hazard ratio 0.22 [95% CI 0.03-1.88] in the 8-14 days group, 1.07 [0.15-7.60] in the 15-28 days group, and 0.76 [0.24-2.39] in the 29-180 days group).DiscussionLong-term dual antiplatelet therapy using cilostazol starting 15-180 days after stroke onset, compared to therapy started 8-14 days after onset, was more effective for secondary stroke prevention than monotherapy without increasing hemorrhage risk.Trial registration informationClinicalTrials.gov NCT01995370; UMIN Clinical Trials Registry 000012180.Classification of evidenceThis study provides Class II evidence that for patients with acute noncardioembolic stroke taking either aspirin or clopidogrel, the addition of cilostazol 15-180 days after stroke onset decreases the risk of recurrent ischemic stroke.

Dataset Information

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Statin and dual antiplatelet therapy for the prevention of early neurological deterioration and recurrent stroke in branch atheromatous disease: a protocol for a prospective single-arm study using a historical control for comparison.

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