Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities

Stroke ◽  
2021 ◽  
Author(s):  
Adam de Havenon ◽  
Kevin N. Sheth ◽  
Tracy E. Madsen ◽  
Karen C. Johnston ◽  
Tanya N. Turan ◽  
...  
Keyword(s):  
Stroke Prevention ◽  
Plasma Lipids ◽  
Gastrointestinal Symptoms ◽  
Cognitive Outcome ◽  
European Medicines Agency ◽  
Stroke Recurrence ◽  
Drug Discontinuation ◽  
Secondary Stroke Prevention ◽  
Long Term Treatment ◽  
Phosphodiesterase Iii Inhibitor

Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol’s pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

Abstract 81: Translesional Pressure Gradient Alters the Relationship Between Blood Pressure and Stroke Recurrence in Symptomatic Intracranial Atherosclerotic Disease

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xueyan Feng ◽  
Ka Lung Chan ◽  
Jill Abrigo ◽  
Linda Lan ◽  
Yannie Soo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Pressure Gradient ◽  
Stroke Prevention ◽  
Primary Outcome ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Cfd Models ◽  
Intracranial Atherosclerotic Disease ◽  
The Relationship

Objective: Patients with symptomatic intracranial atherosclerotic stenosis (sICAS) have a high risk of stroke recurrence. There is debate over an optimal blood pressure (BP) lowering target in secondary stroke prevention in such patients, when some factors (e.g., impaired cerebral perfusion) may alter the relationship between BP and risk of stroke recurrence. In this study, we investigated whether translesional pressure gradient across sICAS lesions would also alter such relationship. Methods: We recruited patients with sICAS (50-99% stenosis) confirmed in CT angiography (CTA). Computational fluid dynamics (CFD) models were built based on CTA to simulate blood flow across sICAS and calculate the translesional pressure ratio (PR, the ratio of pressures distal and proximal to a lesion). PR ≤ median was defined as low PR, indicating larger translesional pressure gradient and hence restricted downstream perfusion. The primary outcome was recurrent ischemic stroke in the same territory in 1 year. We investigated the interaction of PR and mean systolic BP (SBP) during follow-up in determining the risk of the primary outcome. Results: Among 157 patients, the median PR was 0.93. Multivariate Cox regression revealed significant PR-SBP interaction on the primary outcome (p=0.025): in patients with normal PR, the risk of primary outcome significantly decreased with lower SBP during follow-up (for 10 mmHg decrement: HR 0.46; p=0.018); however, in those with low PR, mean SBP ≤130 mmHg was associated with significantly increased risk of primary outcome, compared with 130<SBP<150mmHg (HR 5.08; p=0.043) (Figure). Conclusion: Intensive BP lowering may increase the risk of stroke recurrence in sICAS patients with a large translesional pressure gradient, warranting further investigation. PR by CFD models may yield a promising indicator to differentiate sICAS patients for different BP management strategies for better secondary stroke prevention.

scholarly journals Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention

2021 ◽  
Vol 23 (1) ◽  
pp. 51-60
Author(s):  
Yuesong Pan ◽  
Zixiao Li ◽  
Jiejie Li ◽  
Aoming Jin ◽  
Jinxi Lin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Secondary Prevention ◽  
Acute Ischemic Stroke ◽  
Stroke Prevention ◽  
Recurrent Stroke ◽  
Antihypertensive Agents ◽  
Residual Risk ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention

Background and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk.Methods Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months.Results Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk.Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

scholarly journals Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Shimeng Liu ◽  
Zongen Gao ◽  
Ran Meng ◽  
Haiqing Song ◽  
Tianping Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Stroke Prevention ◽  
Stroke Recurrence ◽  
Large Sample Size ◽  
Cerebrovascular Event ◽  
Secondary Stroke Prevention ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Minor Ischemic Stroke ◽  
Cerebrovascular Events

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months.Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days.Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions.Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.

Abstract 13293: Detection of Atrial Fibrillation by Implantable Loop Recorders Following Cryptogenic Stroke: A Retrospective Study of Predictive Factors and Outcomes

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sara Samaan ◽  
Beshoy Nazeer ◽  
Heidi Stoute ◽  
Wei Zhao ◽  
Susanna Szpunar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Multivariable Analysis ◽  
Cryptogenic Stroke ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Recurrence Rates ◽  
Implantable Loop Recorders

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.

scholarly journals Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review

2021 ◽  
Author(s):  
Irum D. Kotadia ◽  
Iain Sim ◽  
Rahul Mukherjee ◽  
Daniel O’Hare ◽  
Amedeo Chiribiri ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Structural Changes ◽  
Stroke Risk ◽  
Cryptogenic Stroke ◽  
Embolic Stroke ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Unknown Source ◽  
The Relationship

Abstract Approximately one‐third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one‐third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

Abstract TP415: Regular Home Blood Pressure Monitoring Reduces the Risk of Stroke Recurrence

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Wenjun Deng ◽  
David McMullin ◽  
Lindsay Fisher ◽  
Richard Chou ◽  
Jared Jacobson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Stroke Prevention ◽  
Blood Pressure Monitoring ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Stroke Patients ◽  
Self Monitoring ◽  
Recurrent Strokes ◽  
At Home

Background: High blood pressure (BP) is a well recognized risk factor for ischemic stroke, and aggressive BP control is critical for secondary stroke prevention. However, hypertensive (HTN) outpatients are often found to have uncontrolled BP, in part due to poor compliance with daily at-home BP monitoring and consequent poor medication adherence. Here, we explore the association of patient home BP self-monitoring compliance with stroke recurrence. Method: Ischemic stroke patients with pre-existing HTN were prospectively recruited in accordance with IRB protocol for this observational study. All patients were trained on BP self-monitoring as per standard of care, and were asked to monitor BP at home daily consistently for 2 weeks. BP monitoring compliance, per completion of BP log, was assessed at each follow-up clinical visit by an investigator blinded to patient outcome. Stroke recurrence was followed for 5 years and independently adjudicated by two vascular neurologists. Result: In a total of 219 patients, only 36 patients (16.4%) were compliant in completing the home BP log as instructed. The compliant and non-compliant groups showed no baseline difference and no medication usage difference (p>0.05) (Table 1). Compliance with at-home BP monitoring was associated with well controlled systolic (p<0.001) and diastolic BP (p<0.001). Of note, 30 patients (16.4%) had recurrent strokes in the non-compliant group, while there were no recurrent strokes in the compliant group. BP self-monitoring compliance is associated with reduced incidence of stroke recurrence (p=0.030) and the significance remains robust after adjusting for multiple confounders (p=0.029) (Table 2). Conclusion: Regular home BP monitoring is associated with lower risk of stroke recurrence in HTN stroke patients. Study in expanded patient cohort is ongoing to leverage technology for better home BP monitoring and to create incentives for compliant behavior for better secondary stroke prevention.

scholarly journals Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients

2000 ◽  
pp. 577-584 ◽  
Author(s):  
JA Verhelst ◽  
AM Pedroncelli ◽  
R Abs ◽  
M Montini ◽  
MV Vandeweghe ◽  
...  
Keyword(s):  
Slow Release ◽  
Glycosylated Hemoglobin ◽  
Gastrointestinal Symptoms ◽  
Liver Function Tests ◽  
Term Treatment ◽  
Drug Discontinuation ◽  
Open Label ◽  
Long Term Treatment ◽  
Igf I ◽  
One Year

OBJECTIVE: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. DESIGN: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30mg intramuscular every 7-14 days. METHODS: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year. RESULTS: Treatment resulted in a significant improvement in the symptom score from 2.69+/-0.27 to 1.06+/-0.17 (P<0.0001). Serum IGF-I levels fell from 699+/-38microg/l at baseline to 399+/-26microg/l (P<0.0001, n=60) after one month, after which levels remained stable: 480+/-37microg/l after 6 months (n=54) and 363+/-32microg/l after one year (n=46). GH levels dropped from 13.8+/-3.2microg/l to 4.3+/-0.7microg/l after one month (P<0.0001, n=60) and remained stable thereafter: 3.9+/-0.4microg/l (n=54) after 6 months and 3.5+/-1.1microg/l after one year (n=46). Twenty-nine out of 66 patients (44%) attained a normal age-corrected IGF-I level and 30 patients (45%) attained a GH level below 2.5microg/l. Pituitary adenoma shrinkage of at least 25% was found in 5 of 14 patients (36%) after one year. Side effects were mainly transient gastrointestinal symptoms and pain at the injection site, resulting in drug discontinuation in only 6 patients (9%). Two patients developed new gall stones. No difference was found between subcutaneous octreotide and lanreotide SR in efficacy and almost all patients preferred the easier dose administration of lanreotide SR. CONCLUSIONS: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-I levels and symptoms and is well tolerated in the majority of patients. Compared with subcutaneous octreotide, lanreotide SR considerably improves patient's acceptance of therapy while having the same overall efficacy.

scholarly journals Stroke Recurrence in Nigerian Children With Sickle Cell Disease: Evidence for a Secondary Stroke Prevention Trial

2019 ◽  
Vol 95 ◽  
pp. 73-78 ◽  
Author(s):  
Shehu U. Abdullahi ◽  
Michael R. DeBaun ◽  
Lori C. Jordan ◽  
Mark Rodeghier ◽  
Najibah A. Galadanci
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Prevention Trial ◽  
Stroke Recurrence ◽  
Secondary Stroke Prevention ◽  
Cell Disease ◽  
Nigerian Children
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