Abstract WP422: Mechanisms of Recurrent Ischemic Stroke Under Medical versus Device Therapy: Long Term Follow-up in the RESPECT PFO Trial

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
David E Thaler ◽  
John Carroll ◽  
Jeffrey Saver ◽  
Richard Smalling ◽  
Diane Book ◽  
...  
Keyword(s):  
Recurrent Events ◽  
Statistical Significance ◽  
Cryptogenic Stroke ◽  
Standard Of Care ◽  
Primary Analysis ◽  
Intention To Treat ◽  
Long Term Follow Up ◽  
Pfo Closure

Introduction: The RESPECT trial evaluated the superiority of patent foramen ovale (PFO) closure over standard-of-care medical management (MM) in patients with PFO and cryptogenic stroke (CS). Hypothesis: Analysis of stroke mechanisms and topography of recurrent events will provide insight into the clinical efficacy of PFO closure. Methods: RESPECT is a prospective, multicenter, randomized event-driven trial of PFO closure vs. MM in patients with CS and PFO. Patients were randomized to treatment in a 1:1 ratio. The primary results were analyzed and reported when the target of 25 events were adjudicated (NEJM 2013; 368:1092-100). At that time, mean follow-up was 2.6 years, range 0-8.1 years. Prospective follow-up has continued. Recurrent strokes were assigned phenotypes using the ASCOD system by investigators blinded to treatment assignment. Results: 980 subjects were randomized to PFO closure (n=499) or MM (n=481). The primary analysis in the intention-to-treat population after a mean follow-up of 2.6 years exhibited a hazard ratio of 0.49 favoring closure that did not reach statistical significance (p=0.08). The per-protocol cohort demonstrated a significant reduction in the primary endpoint in favor of closure (HR 0.37, p=0.03). Among the initial 25 recurrent ischemic strokes, MM patients more often had superficial or multiple-penetrator territory infarcts (12 vs 4) and infarcts of larger size (69% vs 14%, p=0.06). Since the primary results report, follow-up has continued for an additional 3.5 years and additional recurrent infarcts have been observed. Long-term stroke rates, phenotyping, and topography will be presented. Conclusions: Our prior reports suggest that PFO closure was associated with prevention of stroke subtypes particularly associated with PFO, including superficial and larger infarcts. Long-term safety, efficacy, and stroke mechanisms, with >4000 patient-years of follow-up will be presented.

scholarly journals Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Elisabetta Mariucci ◽  
Andrea Donti ◽  
Luisa Salomone ◽  
Marta Marcia ◽  
Marta Guidarini ◽  
...  
Keyword(s):  
Recurrent Stroke ◽  
Cryptogenic Stroke ◽  
Vascular Risk Factor ◽  
Vascular Risk ◽  
Long Term Follow Up ◽  
Recurrent Strokes ◽  
Few Data ◽  
Pfo Closure

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.

Abstract 72: Procedural and Long Term Safety of PFO Closure in Cryptogenic Stroke: Insights from the RESPECT Trial

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Richard W Smalling ◽  
John Carroll ◽  
Jeffrey Saver ◽  
David Thaler ◽  
Todd Bull ◽  
...  
Keyword(s):  
Medical Management ◽  
Recurrent Stroke ◽  
Cryptogenic Stroke ◽  
Dropout Rate ◽  
Small Subset ◽  
Post Procedure ◽  
Venous Thromboembolic Events ◽  
Pfo Closure

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.

scholarly journals Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment elevation myocardial infarction but not with recurrent events during long-term follow-up

2018 ◽  
Vol 108 (5) ◽  
pp. 520-538 ◽  
Author(s):  
Mathijs C. Bodde ◽  
Maaike P. J. Hermans ◽  
J. Wouter Jukema ◽  
Martin J. Schalij ◽  
Willem M. Lijfering ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Recurrent Events ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment ◽  
Long Term Follow Up

Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Primary Analysis ◽  
Free Survival ◽  
Anti Cancer ◽  
Long Term Follow Up ◽  
Grade 3

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.

scholarly journals Patent foramen ovale closure following cryptogenic stroke or transient ischaemic attack: Long-term follow-up of 301 cases

2015 ◽  
Vol 86 (6) ◽  
pp. 1078-1084 ◽  
Author(s):  
Mikaeil Mirzaali ◽  
Maureen Dooley ◽  
Dylan Wynne ◽  
Nina Cooter ◽  
Lorraine Lee ◽  
...  
Keyword(s):  
Transient Ischaemic Attack ◽  
Patent Foramen Ovale ◽  
Cryptogenic Stroke ◽  
Foramen Ovale ◽  
Long Term Follow Up ◽  
Ischaemic Attack

scholarly journals Malondialdehyde can predict survival in hemodialysis patients

2016 ◽  
Vol 89 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Crina Claudia Rusu ◽  
Simona Racasan ◽  
Ina Maria Kacso ◽  
Diana Moldovan ◽  
Alina Potra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cox Model ◽  
Statistical Significance ◽  
Morbidity And Mortality ◽  
Protein Carbonyls ◽  
Cross Sectional ◽  
Long Term Follow Up ◽  
Cv Disease

Background and aims. Cardiovascular (CV) disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Kidney disease is associated with increased oxidative stress (OS), a nontraditional CV risk factor. Few studies evaluate the effect of OS markers on CV events (CVE) and survival in HD patients. The aim of this study is to examine potential determinants of OS markers and their predictive role on survival and CV morbidity and mortality in HD patients during a long-term follow-up (108 months).  Methods. We conducted an analytical cross-sectional prospective observational study, carried on a cohort of randomly selected HD patients. We registered in 44 HD patients baseline characteristics, OS markers, mortality and CVE over a period of 108 months and we used statistical analysis (descriptive, Kaplan-Meier, univariate and multivariate Cox model) for interpretation.Results. Bound malondialdehyde (bMDA) was positively correlated with serum calcium, protein carbonyls (PC) were inversely correlated with diastolic blood pressure (DBP) and directly correlated with ferritin, NOx was directly correlated with ceruloplasmin) and serum albumin. Of the measured OS markers only bMDA was related to survival (HR=3.29 95% CI (1.28-8.44), p=0.01), and approached statistical significance in the effect on CV mortality (HR=2.85 95% CI (0.88-9.22), p=0.07). None of the measured OS markers was associated with CVE.Conclusions. bMDA has a strong predictive value on survival in HD patients in a long-term follow-up (9 years). Its value is correlated with CV mortality but is not a predictor of CV events. Regular assessment of MDA in HD patients and the development of strategies aimed at reducing oxidative stress in these patients might be beneficial.

scholarly journals Bilateral Sander IV calcaneus fractures: Primary fusion or fixation?

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0006
Author(s):  
Rajiv Shah
Keyword(s):  
Internal Fixation ◽  
Open Reduction ◽  
Standard Of Care ◽  
Calcaneus Fracture ◽  
Subtalar Fusion ◽  
Fall From Height ◽  
Long Term Follow Up ◽  
Calcaneus Fractures

Category: Trauma Introduction/Purpose: Primary subtalar fusion for Sander IV calcaneus fractures was considered to be the standard of care till recent past. Presently debate is on whether to manage Sander IV calcaneus fracture cases with primary subtalar fusion or with open reduction and internal fixation. Bilateral Sander IV calcaneus fractures are seen in cases with fall from height. No study has ever been conducted till date to compare the results of primary fusion of a Sander IV calcaneus fracture on one side and open reduction and internal fixation on another side in cases with bilateral Sander IV calcaneus fractures. We present a study comparing the results of primary fusion versus open reduction and internal fixation for bilateral sander IV calcaneus fracture cases. Methods: Twelve cases with bilateral closed Sander IV calcaneus fractures where included in the present study. Cases were operated between four to six weeks by a single surgeon after the appearance of wrinkles. All right sided fractures underwent open reduction and internal fixation with proximal tibia grafting. While all left-sided fractures underwent subtalar fusion with the use of ipsilateral anterior iliac crest grafts. Cases were followed up for 24 months. Results: Though operative time was more in the fusion group wound problems were equal in both the groups. Four months of average time to union was the same in both the groups and so was time to return to work. At two years, the AOFAS score was slightly better in the fusion group but it was not statistically significant. Conclusion: Primary subtalar fusion is with almost similar results as those with open reduction and internal fixation in bilateral Sander IV at 24 months. Long term follow up with more number of cases is required to prove the benefit of one over other.

Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4006-4006 ◽  
Author(s):  
John Neil Primrose ◽  
Richard Fox ◽  
Daniel H. Palmer ◽  
Raj Prasad ◽  
Darius Mirza ◽  
...  
Keyword(s):  
Randomized Study ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Resection Margins ◽  
Primary Analysis ◽  
Tract Cancer ◽  
Intention To Treat ◽  
And Gender ◽  
Ecog Ps

4006 Background: Despite improvements in multidisciplinary management, BTC has a poor outcome. Approximately 20% of cases are suitable for surgical resection with a 5 year survival of < 10%. BILCAP aimed to determine whether capecitabine (Cape) improves overall survival (OS) compared to observation (Obs) following radical surgery. Methods: Patients with completely-resected cholangiocarcinoma (CCA) or gallbladder cancer (including liver and pancreatic resection, as appropriate), with adequate biliary drainage, no ongoing infection, adequate renal, haematological and liver function, and ECOG PS ≤2, were randomized 1:1 to Cape (1250 mg/m2 D1-14 every 21 days, for 8 cycles) or Obs. Randomization was minimized on tumor site, resection status, ECOG PS and surgical center. The primary outcome was OS in the intention to treat (ITT) population. 410 patients were needed to detect a hazard ratio (HR) of 0.69 (2-sided α = 0.05 and 80% power). HR was estimated by Cox survival model with adjustment for the minimization factors. Primary analysis performed with at least 24 months (m) follow-up. Results: 447 participants were randomized to Cape (n = 223) or Obs (n = 224) from 44 UK sites between 2006-2014. Median age was 63y (IQR 55, 69) and 201 (45%), 232 (52%), and 14 (3%) patients were ECOG PS 0, 1 and 2 respectively. Primary site: 84 (19%) intrahepatic, 128 (28%) hilar, 156 (35%) extrahepatic CCA and 79 (18%) muscle-invasive gallbladder cancers. Resection margins: R0 in 279 (62%) and R1 in 168 (38%); 207 (46%) were node-negative. Follow up was at least 36m in > 80% of surviving patients. By ITT analysis (n = 447), median OS was 51m (95%CI 35, 59) for Cape and 36m (95%CI 30, 45) for Obs, HR 0.80 (95%CI 0.63, 1.04; p = 0.097). Sensitivity analyses with adjustment for nodal status, grade of disease and gender indicated HR 0.71 (95%CI 0.55, 0.92 p < 0.01). In the per-protocol analysis (Cape n = 210, Obs n = 220) median OS was 53m (95%CI 40, NR) for Cape and 36m (95%CI 30, 44) for Obs, HR 0.75 (95%CI 0.58, 0.97; p = 0.028). Median RFS (ITT) was 25m (95%CI 19, 37) for Cape and 18m (95%CI 13, 28) for Obs. Grade 3-4 toxicity was less than anticipated. Conclusions: Cape improves OS in BTC when used as adjuvant and should become standard of care. Clinical trial information: ISRCTN72785446.

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