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Journal of the American Heart... Jun 2018We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet... (Meta-Analysis)
Meta-Analysis
Closure, Anticoagulation, or Antiplatelet Therapy for Cryptogenic Stroke With Patent Foramen Ovale: Systematic Review of Randomized Trials, Sequential Meta-Analysis, and New Insights From the CLOSE Study.
BACKGROUND
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing patent foramen ovale (PFO) closure, anticoagulation, and antiplatelet therapy to prevent stroke recurrence in patients with PFO-associated cryptogenic stroke.
METHODS AND RESULTS
We searched Medline, Cochrane Library, and EMBASE through March 2018. The primary outcome was stroke recurrence. Pooled incidences, hazard ratios, and risk ratios (RRs) were calculated in random-effects meta-analyses. PFO closure was associated with a lower risk of recurrent stroke compared with antithrombotic therapy (antiplatelet therapy or anticoagulation: 3560 patients from 6 RCTs; RR=0.36, 95% CI: 0.17-0.79; I=59%). The effect of PFO closure on stroke recurrence was larger in patients with atrial septal aneurysm or large shunt (RR=0.27, 95% CI, 0.11-0.70; I=42%) compared with patients without these anatomical features (RR=0.80, 95% CI, 0.43-1.47; I=12%). Major complications occurred in 2.40% (95% CI, 1.03-4.25; I=77%) of procedures. New-onset atrial fibrillation was more frequent in patients randomized to PFO closure versus antithrombotic therapy (RR=4.33, 95% CI, 2.37-7.89; I=14%). One RCT compared PFO closure versus anticoagulation (353 patients; hazard ratio=0.14, 95% CI, 0.00-1.45) and 2 RCTs compared PFO closure versus antiplatelet therapy (1137 patients; hazard ratio=0.18, 95% CI, 0.05-0.63; I=12%). Three RCTs compared anticoagulation versus antiplatelet therapy, with none showing a significant difference.
CONCLUSIONS
PFO closure is superior to antithrombotic therapy to prevent stroke recurrence after cryptogenic stroke. The annual absolute risk reduction of stroke was low, but it has to be tempered by a substantial time at risk (at least 5 years) in young and middle-aged patients. PFO closure was associated with an increased risk of atrial fibrillation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiac Catheterization; Embolism, Paradoxical; Female; Foramen Ovale, Patent; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Stroke; Treatment Outcome; Young Adult
PubMed: 29910193
DOI: 10.1161/JAHA.117.008356 -
The Lancet. Neurology Jul 2018Percutaneous closure of patent foramen ovale (PFO) has been shown to be superior to medical treatment alone for prevention of recurrent stroke after cryptogenic... (Meta-Analysis)
Meta-Analysis
Prevalence of patent foramen ovale in cryptogenic transient ischaemic attack and non-disabling stroke at older ages: a population-based study, systematic review, and meta-analysis.
BACKGROUND
Percutaneous closure of patent foramen ovale (PFO) has been shown to be superior to medical treatment alone for prevention of recurrent stroke after cryptogenic transient ischaemic attack or non-disabling stroke in patients aged 60 years or younger. The justification for trials in older patients with transient ischaemic attack or stroke depends on whether PFO is shown to be associated with cryptogenic events at older ages, for which existing evidence is conflicting, and on the population burden of PFO-associated events. Therefore, we did a population-based screening study using contrast-enhanced transcranial Doppler (bubble-TCD) to detect probable PFO as indicated by a right-to-left shunt (RLS); we also did a systematic review and meta-analysis to compare our results with previous studies.
METHODS
In this population-based study, nested in the Oxford Vascular Study (OXVASC), we established the prevalence of any RLS, and of large RLS (>20 microbubbles), in consecutive patients attending a rapid-access transient ischaemic attack and stroke clinic, or at 1-month follow-up after stroke unit admission, with transient ischaemic attack or non-disabling ischaemic stroke, comparing cryptogenic events with those of known cause (according to Trial of Org 10172 in Acute Stroke Treatment [TOAST] criteria). We stratified participants by age, and extrapolated data to the UK population. We also did a systematic review of published studies of PFO prevalence (using transthoracic or transoesophageal echocardiography or bubble-TCD) according to stroke subtype, which included older patients and reported age-specific results, and determined by meta-analysis (including the OXVASC data) the pooled odds ratio (95% CI) of finding PFO of any size in cryptogenic events compared with events of known cause, stratified by screening modality (transthoracic or transoesophageal echocardiography or bubble-TCD). The study protocol is registered with PROSPERO, number CRD42018087074.
FINDINGS
Among 572 consecutive patients with transient ischaemic attack or non-disabling stroke between Sept 1, 2014, and Oct 9, 2017 (439 [77%] patients aged >60 years, mean age 70·0 years [SD 13·7]), bubble-TCD was feasible in 523 patients (91%) of whom 397 were aged older than 60 years. Compared with those with transient ischaemic attack or stroke of known cause, patients with cryptogenic events had a higher prevalence of RLS overall (odds ratio [OR] 1·93, 95% CI 1·32-2·82; p=0·001), and in those aged older than 60 years (2·06, 1·32-3·23; p=0·001). When we pooled the OXVASC data with that from two previous smaller studies of bubble-TCD in patients aged 50 years or older, we found an association between RLS and cryptogenic events (OR 2·35, 95% CI 1·42-3·90; p=0·0009; p=0·15), which was consistent with the equivalent estimate from transoesophageal echocardiography studies (2·20, 1·15-4·22; p=0·02; p=0·02). No data on large RLS in patients with TOAST-defined cryptogenic events compared with other events were available from previous studies, but we found no evidence that the association was diminished in such cases. Of 41 patients with large RLS and cryptogenic transient ischaemic attack or non-disabling stroke in our study, 25 (61%) were aged older than 60 years, which extrapolates to 5951 patients per year in the UK (data from mid-2016).
INTERPRETATION
Bubble-TCD was feasible in most older patients with transient ischaemic attack or non-disabling stroke, the association of RLS with cryptogenic events remained at older ages, and the population burden of PFO-associated events is substantial. Randomised trials of PFO closure at older ages are required and should be feasible.
FUNDING
National Institute for Health Research, Oxford Biomedical Research Centre, Wellcome Trust, and Wolfson Foundation.
Topics: Aged; Aged, 80 and over; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Middle Aged; Prevalence; Stroke; Ultrasonography, Doppler, Transcranial
PubMed: 29887162
DOI: 10.1016/S1474-4422(18)30167-4 -
CNS Neuroscience & Therapeutics Oct 2018Previous review from randomized controlled trials (RCT) showed that patients with cryptogenic stroke may benefit from patent foramen ovale (PFO) closure. However, the... (Meta-Analysis)
Meta-Analysis
Patent foramen ovale closure for patients with cryptogenic stroke: A systematic review and comprehensive meta-analysis of 5 randomized controlled trials and 14 observational studies.
BACKGROUND
Previous review from randomized controlled trials (RCT) showed that patients with cryptogenic stroke may benefit from patent foramen ovale (PFO) closure. However, the findings from the systematic review were not clear when observational studies were also included.
METHODS
We searched MEDLINE, Embase, and Cochrane databases. The primary endpoints were recurrent stroke or transient ischemic attack (TIA). The secondary outcomes were all-cause death, atrial fibrillation (AF), and hemorrhagic events.
RESULTS
Five randomized trials and fourteen observational studies (6301 participants) were eligible. PFO closure was superior to medical therapy for stroke prevention risk ratios ([RR], 0.38; 95% CI, 0.24-0.60), but showed increased risk of AF (RR, 4.96; 95% CI, 2.31-10.7). There was no significant difference in TIA recurrence, death, and hemorrhagic events. Subgroup analyses showed that patients with factors such as substantial residual shunt, the presence of atrial septal aneurysm (ASA), male, and age <45 years had a lower risk of recurrent stroke when PFOs were closed.
CONCLUSIONS
In patients with cryptogenic stroke, PFO closure does appeared to be superior to medical therapy in stroke prevention, with an increased incidence of AF. Male, age <45 years, substantial residual shunt, and the history of ASA are the factors that will predict the benefit when PFO is closed.
Topics: Databases, Bibliographic; Endovascular Procedures; Fibrinolytic Agents; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Observational Studies as Topic; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 29804325
DOI: 10.1111/cns.12980 -
JACC. Cardiovascular Interventions Apr 2018
Meta-Analysis
Topics: Cardiac Catheterization; Foramen Ovale, Patent; Humans; Migraine Disorders; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29673517
DOI: 10.1016/j.jcin.2018.01.232 -
Cerebrovascular Diseases (Basel,... 2018The optimal strategy of secondary stroke prevention in patients with patent foramen ovale (PFO) is controversial. This study was performed to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal strategy of secondary stroke prevention in patients with patent foramen ovale (PFO) is controversial. This study was performed to evaluate the efficacy and safety of the device closure (DC) versus the medical therapy (MT) in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO.
SUMMARY
Randomized controlled trials with active and control groups receiving the DC plus MT and MT alone in patients with history of cryptogenic stroke/TIA and diagnosis of PFO were systematically searched. The main efficacy outcome was stroke recurrence. Subgroup-analyses were performed according to age, shunt size, and presence of atrial septal aneurysm (ASA). Safety endpoints included any serious adverse event (SAE), atrial fibrillation (AF), and major bleeding complications. Risk ratios (RRs) and hazard ratios (HRs) with 95% CIs were estimated. Five trials were included, involving 3,440 participants (DC = 1,829, MT = 1,611). There was a protective effect of closure in the risk of recurrent stroke (RR 0.43 [0.21-0.90]; p = 0.024; HR = 0.39 [0.19-0.83]; p = 0.014). The benefit of PFO closure was significant in patients with PFO associated with substantial right-to-left shunt or ASA. There were no differences in the risks of SAEs and major bleedings between the groups. The rate of new-onset AF was higher in the DC than in the MT arm (RR 4.46 [2.35-8.41]; p < 0.001). Successful device implantation and effective PFO closure were achieved in 96 and 91% of the patients respectively. Key Messages: In selected adult patients with PFO and history of cryptogenic stroke, the DC plus MT is more effective to prevent stroke recurrence and is associated with an increased risk of new-onset AF compared to the MT alone.
Topics: Adult; Cardiac Catheterization; Cardiovascular Agents; Female; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Male; Middle Aged; Protective Factors; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Secondary Prevention; Stroke; Time Factors; Treatment Outcome
PubMed: 29649819
DOI: 10.1159/000488401 -
BMC Cardiovascular Disorders Mar 2018Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patent foramen ovale (PFO) closure has emerged as a secondary prevention option in patients with PFO and cryptogenic stroke. However, the comparative efficacy and safety of percutaneous closure and medical therapy in patients with cryptogenic stroke and PFO remain unclear.
METHODS
Randomized controlled trials (RCTs) and comparative observational studies that compared PFO closure against medical therapy, each with a minimal of 20 patients in the closure arm and 1-year follow-up were included.
RESULTS
We analyzed 6961 patients from 20 studies (5 RCTs and 15 observational studies) with a median follow-up of 3.1 years. Moderate-quality evidence showed that PFO closure was associated with a significantly lower incidence of the composite outcome of ischemic stroke, transient ischemic attack (TIA), or all-cause death (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38 to 0.85; P = 0.006), mainly driven by lower incidence of stroke (OR: 0.39; 95% CI: 0.24 to 0.63; P < 0.001). The numbers needed to treat were 43 and 39 for the composite outcome and recurrent ischemic stroke respectively. PFO closure increased the risks for atrial fibrillation or atrial flutter (OR: 5.74; 95% CI: 3.08 to 10.70; P < 0.001; high-quality evidence) and pulmonary embolism (OR: 3.03; 95% CI: 1.06 to 8.63; P = 0.038; moderate-quality evidence), with the numbers needed to harm being 30 and 143 respectively. The risks for TIA, all-cause death, and major bleeding were not statistically different. Analyses limited to RCTs showed similar findings, as did a series of other subgroup analyses.
CONCLUSION
In conclusion, PFO closure reduced the incidences of stroke and the composite outcome of ischemic stroke, TIA, or all-cause death, but increased risks for atrial fibrillation or atrial flutter and pulmonary embolism compared with medical therapy.
Topics: Adult; Atrial Fibrillation; Atrial Flutter; Cardiac Catheterization; Cardiovascular Agents; Female; Foramen Ovale, Patent; Humans; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Observational Studies as Topic; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stroke; Time Factors; Treatment Outcome
PubMed: 29499641
DOI: 10.1186/s12872-018-0780-x -
Kardiologia Polska 2018The measurement of health-related quality of life (HRQoL) by validated generic instruments, such as EQ-5D, has become an increasingly important tool for the assessment...
BACKGROUND
The measurement of health-related quality of life (HRQoL) by validated generic instruments, such as EQ-5D, has become an increasingly important tool for the assessment of health care in a wide range of diagnoses.
AIM
We aimed to systematically review EQ-5D literature on cardiovascular diseases in eight Central and Eastern European (CEE) countries.
METHODS
A structured literature search was conducted in MEDLINE, EMBASE, Web of Science, CINAHL, PsycINFO, Cochrane Library, and the EuroQol website up to November 2016. Original cardiovascular-related studies that reported EQ-5D results were included.
RESULTS
Of the 36 papers, 17 reported EQ-5D index scores. Most studies were performed in Poland (n = 24, 67%). The most common diagnosis regarding the number of publications and population size was ischaemic heart disease (n = 13, N = 6394), followed by atrial fibrillation (n = 4, N = 1052). The average EQ-5D index scores ranged from 0.61 to 0.88 and from 0.66 to 0.95 for patients before and after cardiac procedure/surgery, respectively (including angioplasty, coronary artery bypass grafting, ablation, surgical correction of septal defects, transcatheter aortic valve implantation [TAVI]). In all studies baseline scores were lower than the repeated assessments after the procedure, with the most substantial improvement of 0.24 in high-risk elderly patients after TAVI. Studies which did not assess invasive treatment reported mean EQ-5D index scores ranging from 0.18 to 0.80.
CONCLUSIONS
The number of cardiovascular-related studies reporting HRQoL using EQ-5D has consistently increased in CEE countries over the past decade and is outstanding compared with other clinical fields. The EQ-5D index and EQ VAS scores varied based on the disease severity, patient characteristics, and treatment protocol.
Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Europe, Eastern; Female; Humans; Male; Middle Aged; Quality of Life; Young Adult
PubMed: 29350378
DOI: 10.5603/KP.a2018.0033 -
The American Journal of Medicine May 2018Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up.
METHODS
We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models.
RESULTS
Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I = 29.3%).
CONCLUSIONS
In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter.
Topics: Anticoagulants; Atrial Fibrillation; Atrial Flutter; Foramen Ovale, Patent; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 29229471
DOI: 10.1016/j.amjmed.2017.11.027 -
BMC Cardiovascular Disorders Jul 2017The association between patent foramen ovale (PFO) and migraine with aura (MA) is well established. However, the benefits of PFO closure are less certain in patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between patent foramen ovale (PFO) and migraine with aura (MA) is well established. However, the benefits of PFO closure are less certain in patients with migraine without aura (MwoA).
METHODS
We systematically searched Pubmed for pertinent clinical studies published from January 2000 to July 2015. The primary end-point was the elimination or significant improvement of migraine symptoms after PFO closure.
RESULTS
Upon screening an initial list of 315 publications, we identified eight studies that included 546 patients. Overall, our analysis indicated a significant improvement of migraine in 81% of MA cases compared to only 63% of MwoA cases. The summary odds ratio was 2.5 (95% confidence interval 1.09-5.73), and the benefits of PFO closure were significantly greater for patients with MA compared to patients with MwoA (P = 0.03).
CONCLUSIONS
The presence of aura provides a reference standard for the clinical selection of patients with migraine for PFO closure intervention.
Topics: Adult; Cardiac Catheterization; Chi-Square Distribution; Female; Foramen Ovale, Patent; Humans; Male; Middle Aged; Migraine with Aura; Migraine without Aura; Odds Ratio; Patient Selection; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28747203
DOI: 10.1186/s12872-017-0644-9 -
Ultrasound in Obstetrics & Gynecology :... Mar 2018The main aim of this systematic review was to evaluate the prevalence and type of associated anomalies in fetuses with heterotaxy diagnosed prenatally on ultrasound; the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The main aim of this systematic review was to evaluate the prevalence and type of associated anomalies in fetuses with heterotaxy diagnosed prenatally on ultrasound; the perinatal outcome of these fetuses was also studied.
METHODS
An electronic search of MEDLINE, EMBASE and CINAHL databases was performed. Only studies reporting the prenatal diagnosis of isomerism were included. Outcomes observed included associated cardiac and extracardiac anomalies, fetal arrhythmia, abnormal karyotype, type of surgical repair and perinatal mortality. The analysis was stratified according to the type of heterotaxy syndrome (left (LAI) or right (RAI) atrial isomerism). Meta-analyses of proportions were used to combine data. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies.
RESULTS
Sixteen studies (647 fetuses) were included in the analysis. Atrioventricular septal defect was the most common associated major cardiac anomaly found both in fetuses with LAI (pooled proportion (PP), 59.3% (95% CI, 44.0-73.7%)), with obstructive lesions of the right outflow tract occurring in 35.5% of these cases, and in fetuses with RAI (PP, 72.9% (95% CI, 60.4-83.7%)). Fetal arrhythmias occurred in 36.7% (95% CI, 26.9-47.2%) of cases with LAI and were mainly represented by complete atrioventricular block, while this finding was uncommon in cases with RAI (PP, 1.3% (95% CI, 0.2-3.2%)). Abnormal stomach and liver position were found, respectively, in 59.4% (95% CI, 38.1-79.0%) and 32.5% (95% CI, 11.9-57.6%) of cases with LAI, and in 54.5% (95% CI, 38.5-70.1%) and 45.9% (95% CI, 11.3-83.0%) of cases with RAI, while intestinal malrotation was detected in 14.2% (95% CI, 2.5-33.1%) of LAI and 27.1% (95% CI, 7.9-52.0%) of RAI cases. Hydrops developed in 11.8% (95% CI, 2.9-25.6%) of fetuses diagnosed prenatally with LAI. Biventricular repair was accomplished in 78.2% (95% CI, 64.3-89.4%) of cases with LAI, while univentricular repair or palliation was needed in 17.0% (95% CI, 9.7-25.9%); death during or after surgery occurred in 26.8% (95% CI, 4.6-58.7%) of LAI cases. Most children with RAI had univentricular repair and 27.8% (95% CI, 15.5-42.1%) died during or after surgery.
CONCLUSIONS
Fetal heterotaxy is associated with a high prevalence of cardiac and extracardiac anomalies. Approximately one quarter of fetuses with heterotaxy died during or after surgery. Abnormal heart rhythm, especially heart block, is common in fetuses with LAI, while this finding is uncommon in RAI. Biventricular repair was common in LAI while univentricular repair was required in the majority of children affected by RAI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Female; Heart Septal Defects, Ventricular; Heterotaxy Syndrome; Humans; Infant, Newborn; Perinatal Death; Pregnancy; Prenatal Diagnosis; Survival Rate; Treatment Outcome; Ultrasonography, Prenatal; Vascular Surgical Procedures
PubMed: 28603940
DOI: 10.1002/uog.17546