Abstract 71: PFO Closure Reduces Long Term Recurrence of Ischemic Stroke: Final Primary and Secondary Population Results From the RESPECT Multicenter Trial

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
David Thaler ◽  
John Carroll ◽  
Jeffrey Saver ◽  
Richard Smalling ◽  
Lee MacDonald ◽  
...  

Introduction: In the intention-to-treat (ITT) analysis of the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial, a trend favoring PFO closure in the primary analytic period (median follow-up 2.1y) was statistically significant with longer follow-up (median 5.9y). Hypotheses: Populations with less clinical trial noise [Per Protocol (PP), As Treated (AT), Device in Place (DIP)] will show > benefit, consistent with a genuine treatment effect of closure. Analysis of strokes without known mechanisms (per ASCOD) or occurring while patients are less subject to non-PFO stroke mechanisms (<60y) will show heightened treatment effect. Methods: RESPECT was a prospective, multicenter, RCT comparing patients assigned 1:1 to PFO closure (Amplatzer PFO Occluder) or to medical management (MM) alone. Data were collected through May 2016. Results: We enrolled 980 patients who were followed for a median of 5.9y (IQR 4.2-8.0, range 0-11). All primary endpoint events were nonfatal ischemic strokes. The efficacy outcome in the ITT population significantly favored device closure over MM alone (HR: 0.55, 95% CI: 0.305 to 0.999, log-rank p=0.046) and was equal (PP) or magnified in the other populations analyzed by treatment actually received. It was also greater if events were excluded when they occurred after patients reached 60y or had a known (non-PFO) mechanism (Table). Conclusions: The final data from RESPECT, after long-term follow-up, show that the benefit of PFO closure seen in the ITT population is magnified in populations that account for treatment crossover and that include the age range in which recurrent ischemic strokes are predominantly cryptogenic. These secondary analyses reinforce the main trial finding that PFO closure with the Amplatzer PFO Occluder is superior to medical therapy alone in preventing recurrent ischemic stroke.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Richard W Smalling ◽  
John Carroll ◽  
Jeffrey Saver ◽  
David Thaler ◽  
Todd Bull ◽  
...  

Background: Complications of percutaneous patent foramen ovale (PFO) closure using the Amplatzer TM PFO Occluder were reported in 2012 after a median follow-up of 2.1 years. The FDA requested an analysis of long-term device safety observed in the Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment (RESPECT) trial. Methods: We randomized patients with cryptogenic stroke and PFO in a 1:1 ratio between PFO closure and medical management alone (MM). Post procedure medical management in the closure arm was 30 days of aspirin and clopidogrel followed by 5 months of aspirin alone and continued medical therapy as per the site neurologist. Medical treatment in the MM arm was a guideline-directed antiplatelet regimen or warfarin. An independent data and safety monitoring board adjudicated all adverse events as serious (SAE) or non-serious, and as procedure, device or protocol related. Results: We enrolled 980 patients (mean age, 45.9 years) at 69 sites who were followed for a median of 5.9 years (IQR 4.2-8.0). Follow-up was unequal – 3141 patient-years in the closure arm vs. 2669 in the MM arm, due to a higher dropout rate in the MM arm. There was less warfarin use in the closure arm vs. the MM arm (109 vs 578 patient-years). There were no study-related deaths. Two patients had procedure-related ischemic strokes (7 days and 3 months post-procedure). SAEs were equally distributed between the two arms: 13.7 in the closure arm vs. 12.4 per 100 patient-years in the MM arm, p=0.17. There was no device thrombus or erosion. The incidence of post procedure AF was not increased in the closure arm. Venous thromboembolic events (VTE) occurred at a higher rate in the closure arm, 0.87 per 100 patient-years vs. 0.22 in the MM arm, p=0.0008. In univariable logistic regression modeling, a remote history of DVT prior to randomization was a significant predictor of VTEs in the closure arm. No VTEs occurring beyond 6 months were attributed to the procedure or the device. Conclusions: These new long-term data reaffirm that the Amplatzer TM PFO Occluder has a low rate of procedure (2.4%) and device (2%) related SAE’s. A small subset of cryptogenic stroke patients have an underlying proclivity to VTE and may need long-term anticoagulation.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jinghao Han ◽  
Yue Kwan Choi ◽  
Wing Kit Leung ◽  
Ming Tung Hui ◽  
Maria Kwan Wa Leung

Abstract Background We aim to document the long-term outcomes of ischemic stroke patients and explore the potential risk factors for recurrent cardiovascular events and all-cause mortality in primary care. Methods A retrospective cohort study performed at two general out-patient clinics (GOPCs) under Hospital Authority (HA) in Hong Kong (HK). Ischemic stroke patients with at least two consecutive follow-up visits during the recruitment period (1/1–30/6/2010) were included. Patients were followed up regularly till the date of recurrent stroke, cardiovascular event, death or 31/12/2018. The primary outcome was the occurrence of recurrent cerebrovascular event including transient ischemic stroke (TIA), ischemic stroke or hemorrhagic stroke. The secondary outcomes were all-cause mortality and coronary artery disease (CAD). We fit cox proportional hazard model adjusting death as competing risk factor to estimate the cause-specific hazard ratio (csHR). Results A total of 466 patients (mean age, 71.5 years) were included. During a median follow-up period of 8.7 years, 158 patients (33.9%) died. Eighty patients (17.2%) had recurrent stroke and 57 (12.2%) patients developed CAD. Age was an independent risk factor for recurrent stroke, CAD and death. Statin therapy at baseline had a protective effect for recurrent stroke (csHR = 0.476; 95% confidence interval [CI] 0.285–0.796, P = 0.005) after adjusting death as a competing risk factor and all-cause mortality (HR = 0.693, 95% CI 0.486–0.968, P = 0.043). In addition, female sex, antiplatelet and a higher diastolic blood pressure (DBP) at baseline were also independent predictors for survival. Conclusions Long term prognosis of ischemic stroke patients in primary care is favorable. Use of statin was associated with a significant decrease in stroke recurrence and mortality. Patients who died had a significant lower DBP at baseline, highlighted the need to consider both systolic and diastolic blood pressure in our daily practice.


2020 ◽  
Author(s):  
Jinghao Han ◽  
Yue Kwan Choi ◽  
Wing Kit Leung ◽  
Eric Ming Tung Hui ◽  
Maria Kwan Wa Leung

Abstract Background: We aim to document the long-term outcomes of ischemic stroke patients and explore the potential risk factors for recurrent cardiovascular events and all-cause mortality in primary care.Methods: A retrospective cohort study performed at two general out-patient clinics (GOPCs) under Hospital Authority (HA) in Hong Kong (HK). Ischemic stroke patients with at least two consecutive follow-up visits during the recruitment period (1/1-30/6/2010) were enrolled. Patients were followed up regularly till the date of recurrent stroke, cardiovascular event, death or 31/12/2018. Risks of recurrent cardiovascular events and death were estimated by Cox proportional hazards model. The primary outcome was the occurrence of recurrent cerebrovascular event including transient ischemic stroke (TIA), ischemic stroke or hemorrhagic stroke. The secondary outcomes were all-cause mortality and coronary heart disease (CHD).Results: A total of 466 patients (mean age, 71.5 years) were enrolled. During a median follow-up period of 8.7 years, 158 patients (33.9%) died. Eighty patients (17.2%) had recurrent stroke and 57 (12.2%) patients developed CHD. Age was an independent risk factor for recurrent stroke, CHD and death. Statin therapy at baseline had a protective effect for recurrent stroke (hazard ratio [HR] =0.454, 95% confidence interval [CI] 0.269-0.766, P=0.003) and all-cause mortality (HR= 0.693, 95% CI 0.486-0.968, P=0.043). In addition, female sex, antiplatelet and a higher diastolic blood pressure (DBP) at baseline were also independent predictors for survival.Conclusions: Long term prognosis of ischemic stroke patients in primary care is favorable. Use of statin was associated with a significant decrease in stroke recurrence and mortality. Patients who died had a significant lower DBP at baseline, highlighted the need to consider both systolic and diastolic blood pressure in our daily practice.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Elisabetta Mariucci ◽  
Andrea Donti ◽  
Luisa Salomone ◽  
Marta Marcia ◽  
Marta Guidarini ◽  
...  

Background. There are few data on the mechanism of recurrent neurological events after transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA. Methods. We retrospectively reviewed PFO closure procedures for the secondary prevention of cryptogenic stroke/TIA performed between 1999 and 2014 in Bologna, Italy. Results. Written questionnaires were completed by 402 patients. Mean follow-up was 7 ± 3 years. Stroke recurred in 3.2% (0.5/100 patients-year) and TIA in 2.7% (0.4/100 patients-year). Ninety-two percent of recurrent strokes were not cryptogenic. Recurrent stroke was noncardioembolic in 69% of patients, AF related in 15% of patients, device related in 1 patient, and cryptogenic in 1 patient. AF was diagnosed after the procedure in 21 patients (5.2%). Multivariate Cox’s proportion hazard model identified age ≥ 55 years at the time of closure (OR 3.16, p=0.007) and RoPE score < 7 (OR 3.21, p=0.03) as predictors of recurrent neurological events. Conclusion. Recurrent neurological events after PFO closure are rare, usually noncryptogenic and associated with conventional vascular risk factors or AF related. Patients older than 55 years of age and those with a RoPE score < 7 are likely to get less benefit from PFO closure. After transcatheter PFO closure, lifelong strict vascular risk factor control is warranted.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Hamm ◽  
O Doerr ◽  
M Haas ◽  
L Schulz ◽  
T Koerschgen ◽  
...  

Abstract Background Patent foramen ovale (PFO) closure is the treatment of choice after cryptogenic stroke according recent evidence. The indication is based on results of several randomized controlled trials; however, the results of these trials may not be extrapolated to a real-world clinical setting. Therefore, the aim of the present study was to evaluate long-term outcome regarding recurrent stroke, migraine, and/or peripheral embolism in patients after PFO closure. Methods We retrospectively analyzed outcomes of consecutive patients undergoing PFO closure from 2011 to 2018 at two interventional sites with respect to periprocedural events occurring during hospitalization and long-term follow-up. Follow-up data were collected from outpatient visits or telephone interviews. Results The analysis included 214 consecutive patients (mean age 52 years; 58% male). The follow-up rate was 96% and the mean follow-up time was 38 (SD 22) months. The index vascular event leading to PFO closure was stroke (n=190; 89%), including patients with repetitive stroke (n=36), embolic myocardial infarction (n=21), and migraine (n=3). One quarter (24.6%) of the population studied had an atrial septal aneurysm (>15 mm). Procedural success was achieved in 98%. There were no procedure-related strokes or deaths. Periprocedural complications occurred in 16 patients (7%): two cases of pericardial tamponade, seven complications at the access site mainly caused by bleeding, two cases of transient atrial fibrillation, and five other complications. The Amplatz Septal Occluder™ was used in two thirds (64.5%) of the cases and the Gore Cardioform™ device in one third (28.6%). Four (2%) patients died during follow-up. None of these patients experienced a recurrent stroke. Ten (5%) other patients experienced a recurrent stroke. Patients with recurrent stroke events were older than patients without recurrent stroke (mean 62.6 [SD 8.8] years vs. mean 52.2 [SD 13.8] years; p=0.015) and had a higher rate of preexisting cerebrovascular occlusive disease (5 [50%] vs. 10 [6%]; p<0.0001). There was no difference in risk for recurrent stroke between patients with one prior stroke and more than one stroke before PFO closure (p=0.71). Atrial fibrillation occurred in 6.6% of the patients during follow-up, but only one of these patients had recurrent stroke. No other anatomic and vascular risk factors or antithrombotic treatments were identified as being predictive of embolic events after closure. Conclusion In this real-world PFO closure cohort the recurrent stroke rate is low, although it is higher than reported in the recent randomized controlled trials. Recurrent strokes after PFO closure may reflect additional comorbid risk factors such as age or cerebrovascular occlusive disease that are unrelated to the potential for paradoxical embolism.


2019 ◽  
Vol 24 (5) ◽  
pp. 558-571 ◽  
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Christopher Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Bielecka-Dabrowa ◽  
P Gasiorek ◽  
A Sakowicz ◽  
M Banach

Abstract Purpose The study aimed to identify echocardiographic, hemodynamic and biochemical predictors of unfavourable prognosis after ischemic strokes of undetermined etiology (ESUS) in patients (pts) at age <65. Methods Out of 520 ischemic stroke pts we selected 64 pts diagnosed with ESUS [mean age 54 (SD: 47–58) years, 42% males] and additional 36 without stroke but with similar risk profile, which were treated as a reference group [age 53 (SD: 47–58) years, 61% males]. All pts underwent echocardiography, non-invasive assessment of hemodynamic parameters using SphygmoCor tonometer (Atcor Med., Australia), HDL subfraction distribution using Lipoprint (Quantimetrix) as well as measurements of selected biomarkers. Follow-up was 12 months. Results At 12-month follow-up 9% of patients had died, and recurrent ischemic stroke also occurred in 9% of patients - only in the ESUS group (Figure). Patients who died had significantly lower levels of LDL and HDL cholesterol (included HDL-8 and -9 subfractions) and higher level of triglicerides (p=0.01, p=0.01, and p=0.02; respectively), lower level of adiponectin (p=0.01), lower value of mean early diastolic (E') mitral annular velocity (p=0.04) and lower diastolic blood pressure (p=0.04). The atrial fibrillation (AF) occurred in 10% of pts during the 12 months (log-rang, p=0.254) (Figure). The log-rank test showed that ESUS group had a significantly poorer outcome of AF in the first 2 months after hospitalization compared to reference group (11% vs 5%, p=0.041). Based on a Kaplan-Meier analysis, the outcome of re-hospitalizationin the 1st year was 28% (18/64) in the ESUS group and 17% (6/36); log-rank, p=0.058. In the multivariate analysis mean early diastolic (E') mitral annular velocity (odds ratio [OR] 0.75, 95% confidence interval [CI]: 0.6–0.94; p=0.01) was significantly associated with CV hospitalizations assessed at 12-month follow-up. The only independent predictor of AF occurrence in the 12-month follow-up was lower value of Tissue Doppler-derived right ventricular systolic excursion velocity S' (OR 0.65, 95% Cl 0.45–0.93; p=0.01). The only independent predictor of recurrent stroke was the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic mitral annular motion as determined by pulsed wave Doppler (E/E') (OR 0.75, 95% CI: 0.6–0.94; p=0.01). E/E' ratio was also independently associated with composite endpoint consisting of death, hospitalization and recurrent stroke (OR 1.90, 95% CI 1.1–3.2, p=0.01). Kaplan-Meier Analysis - survival and AF Conclusions The indices of diastolic dysfunction are significantly associated with unfavourable prognosis after ESUS. There is a robust role for outpatient cardiac monitoring especially during first 2 months after ESUS to detect potential AF. Acknowledgement/Funding The study was financed by research grants no. 502-03/5-139-02/502-54-229-18 of the Medical University of Lodz


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lisha Hou ◽  
Mier Li ◽  
Ju Wang ◽  
Yawen Li ◽  
Qianwen Zheng ◽  
...  

AbstractThe relationship between exercise and stroke recurrence is controversial. This study was designed to test whether an association exists between exercise and ischemic stroke recurrence in first-ever ischemic stroke survivors. Data were collected from January 2010 to June 2016. Baseline information was obtained during face-to-face interviews, and follow-up phone interviews were conducted every 3 months. Exercise type, frequency, intensity, and duration were recorded. Discrete-time survival analysis was used to determine the relationship between exercise and stroke recurrence. 760 first-ever ischemic stroke survivors who were able to exercise were enrolled. After adjusting for covariates, patients who exercised 3.5–7 h per week and more than 7 h per week had a lower relapse risk than patients who did not exercise (3.5–7: OR 0.415; > 7: OR 0.356). Moreover, if the fluctuation of exercise duration was over 4 h, the patients had a higher risk of stroke recurrence than those with variability of less than 2 h (OR 2.153, P = 0.013). Stroke survivors who engage in long-term regular mild exercise (more than 5 sessions per week and lasting on average 40 min per session) have a lower recurrence rate. Irregular exercise increases the risk of stroke recurrence.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Colin Derdeyn ◽  
David Fiorella ◽  
Tanya Turan ◽  
Jean Montgomery ◽  
Bethany Lane ◽  
...  

Purpose: To investigate the incidence and clinical characteristics of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting for symptomatic intracranial stenosis. Methods: Primary endpoints in SAMMPRIS (Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke) after 30 days past enrollment were defined as ischemic stroke in the territory or any stroke or death within 30 days of a subsequent revascularization procedure. Endpoints were independently and blindly adjudicated. Study records and imaging studies of subjects randomized to the stent arm with post-30 day primary endpoints were reviewed. Instent restenosis (ISR) was categorized as severe (>70%), moderate (50-69%) or mild (< 50%) based on consensus of two reviewers. Findings were categorized as definite, probable, or indeterminate based on imaging modality and study quality. Results: 224 subjects were randomized to the stent arm and 33 suffered a primary endpoint within 30 days of enrollment. Nineteen of the remaining 191 subjects (9.9%) suffered a primary endpoint during follow up (median follow up of 32.4 months). Eighteen had an ischemic stroke in the territory and one had a symptomatic intracranial hemorrhage after repeat angioplasty for in stent restenosis (ISR). In the 18 patients with ischemic stroke, the vascular imaging findings were: complete stent occlusion in 2 (1 of these was acutely revascularized and severe underlying ISR was identified), severe ISR by catheter angiography in 5, severe ISR or occlusion by computed tomographic angiography (CTA) in 1, probable ISR by CTA or magnetic resonance angiography (MRA) in 3, moderate stenosis on angiography in 2 (1 with ISR and 1 with a residual stenosis), indeterminate in 2, normal in 2, and not done in 1. Lesion locations included: distal internal carotid (6), petrous carotid (1), basilar (5), middle cerebral (6), and vertebral (1) arteries. Median time to recurrent stroke was 7.7 months from enrollment (2.2 to 28.2 months). Conclusions: The incidence of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting in the SAMMPRIS trial was nearly 10% over a mean follow-up of almost 3 years. In stent restenosis was associated with the majority of recurrent strokes.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tae-Jin Song ◽  
Jinkwon Kim ◽  
Dongbeom Song ◽  
Yong-Jae Kim ◽  
Hyo Suk Nam ◽  
...  

Background: Cerebral microbleeds (CMBs) were predictive of mortality in elderly and considered as a putative marker for risk of intracranial hemorrhage. Stroke patients with non valvular atrial fibrillation (NVAF) require anticoagulation, which increases the risk of hemorrhages. We investigated association of CMBs with the long term mortality in acute ischemic stroke patients with NVAF. Methods: During 6 years , consecutive ischemic stroke patients who had NVAF and who had undergone brain MRI with a gradient-recalled echo sequence were enrolled. Long-term mortality and causes of death were identified using data from Korean National Statistical Office. Survival analysis was performed whether the presence, number and location of CMBs were related with all causes, cardiovascular, and cerebrovascular mortality during follow-up. Results: Total 506 patients were enrolled during the study period and were followed up for median 2.5 years. CMBs were found in 30.8% of patients (156/506). Oral anticoagulation with warfarin was prescribed at discharge in 477 (82.7%) patients. During follow up, 177 (35%) patients died and cerebrovascular death was noted in 93 patients (81 ischemic stroke and 12 hemorrhagic stroke). After adjusting age, sex and significant variables in univariate analysis (p<0.1), multiple CMBs (≥5) were the independent predictor for all-cause, cardiovascular and ischemic stroke mortalities. The strictly lobar CMBs were associated with hemorrhagic stroke mortality in multivariate Cox regression analysis (HR 4.776, p=0.032) (Figure 1). Conclusions: Multiple CMBs were the independent predictor for the long term mortality in stroke patients with NVAF. Among them, patients with strictly lobar CMBs had a high risk of death due to hemorrhagic stroke. Our findings suggest that detection of CMBs in stroke patients with NVAF are of clinical relevance for predicting long term outcome and that particular concern is necessary in those with strictly lobar CMBs for their increased risk of death due to hemorrhagic stroke. Figure 1.


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