BACKGROUND: Observational studies have shown percutaneous patent foramen ovale (PFO) closure to be a safe means of reducing the frequency and duration of migraine.
OBJECTIVE: This study evaluated the efficacy and safety of PFO closure in patients with migraine using evidence-based medicine.
METHODS: The Pubmed (MEDLINE), Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs), cohort studies, and retrospective case series from January 1, 2001, to February 30, 2021. The Jadad scale and R 4.1.0 software were used to assess the quality of the literature and meta-analysis, respectively.
RESULTS: In total, three randomized controlled trials, one pooled study, and eight retrospective case series including 1,165 participants were included in the meta-analysis. Compared with control intervention in migraine, PFO closure could significantly reduce headache frequency (OR = 1.5698, 95% CI: 1.0465-2.3548, p=0.0293) and monthly migraine attacks and monthly migraine days (OR = 0.2594, 95% CI: 0.0790-0.4398, p=0.0048). Subgroup analysis of patients who all completed PFO surgery showed resolution of migraine headache for migraines with aura (OR = 1.5856, 95% CI: 1.0665-2.3575, p=0.0227).
CONCLUSIONS: Treatment with PFO closure could reduce the frequency of headaches and monthly migraine days and is an efficient treatment for migraine attacks with aura.
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.
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.
OBJECTIVES: To analyse the impact of placebo effects on outcome in trials of selected minimally invasive procedures and to assess reported adverse events in both trial arms.
DESIGN: A systematic review and meta-analysis.
DATA SOURCES AND STUDY SELECTION: We searched MEDLINE and Cochrane library to identify systematic reviews of musculoskeletal, neurological and cardiac conditions published between January 2009 and January 2014 comparing selected minimally invasive with placebo (sham) procedures. We searched MEDLINE for additional randomised controlled trials published between January 2000 and January 2014.
DATA SYNTHESIS: Effect sizes (ES) in the active and placebo arms in the trials' primary and pooled secondary end points were calculated. Linear regression was used to analyse the association between end points in the active and sham groups. Reported adverse events in both trial arms were registered.
RESULTS: We included 21 trials involving 2519 adult participants. For primary end points, there was a large clinical effect (ES≥0.8) after active treatment in 12 trials and after sham procedures in 11 trials. For secondary end points, 7 and 5 trials showed a large clinical effect. Three trials showed a moderate difference in ES between active treatment and sham on primary end points (ES ≥0.5) but no trials reported a large difference. No trials showed large or moderate differences in ES on pooled secondary end points. Regression analysis of end points in active treatment and sham arms estimated an R(2) of 0.78 for primary and 0.84 for secondary end points. Adverse events after sham were in most cases minor and of short duration.
CONCLUSIONS: The generally small differences in ES between active treatment and sham suggest that non-specific mechanisms, including placebo, are major predictors of the observed effects. Adverse events related to sham procedures were mainly minor and short-lived. Ethical arguments frequently raised against sham-controlled trials were generally not substantiated.
OBJECTIVES: The aim of this meta-analysis was to determine the accuracy of transcranial Doppler (TCD) compared with transesophageal echocardiography (TEE) as the reference.
BACKGROUND: Right-to-left shunting (RLS), usually through a patent foramen ovale (PFO), has been associated with migraine, cryptogenic stroke, and hypoxemia. With emerging observational studies and clinical trials on the subject of PFO, there is a need for accurate diagnosis of PFO in patients with these conditions, and those being considered for transcatheter closure. Although a TEE bubble study is the current standard reference for diagnosing PFO, the TCD bubble study may be a preferable alternative test for RLS because of its high sensitivity and specificity, noninvasive nature, and low cost.
METHODS: A systematic review of Medline, the Cochrane Library, and Embase was done to look for all the prospective studies assessing intracardiac RLS using TCD compared with TEE as the reference; both tests were performed with a contrast agent and a maneuver to provoke RLS in all studies.
RESULTS: A total of 27 studies (29 comparisons) with 1,968 patients (mean age 47.8 ± 5.7 years; 51% male) fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TCD were 97% and 93%, respectively. Likewise, the positive and negative likelihood ratios were 13.51 and 0.04, respectively. When 10 microbubbles was used as the embolic cutoff for a positive TCD study, TCD produced a higher specificity compared with when 1 microbubble was used as the cutoff (p = 0.04); there was, however, no significant change in sensitivity (p = 0.29).
CONCLUSIONS: TCD is a reliable, noninvasive test with excellent diagnostic accuracies, making it a proficient test for detecting RLS. TCD can be used as a part of the stroke workup and for patients being considered for PFO closure. If knowledge of the precise anatomy is required, then TEE can be obtained before scheduling a patient for transcatheter PFO closure.
BACKGROUND: Migraine headache and the presence of a patent foramen ovale have been associated with each other, although the precise pathophysiological mechanism(s) are uncertain. The purpose of this systematic review was to identify the extent of patent foramen ovale prevalence in migraineurs and to determine whether closure of a patent foramen ovale would improve migraine headache.
METHODS: An electronic literature search was performed to select studies between January 1980 and February 2013 that were relevant to the prevalence of patent foramen ovale and migraine, and the effects of intervention(s) on migraine attacks. Of the initial 368 articles presented by the initial search, 20 satisfied the inclusion criteria assessing patent foramen ovale prevalence in migraineurs and 21 presented data on patent foramen ovale closure.
RESULTS: In case series and cohort studies, patent foramen ovale prevalence in migraineurs ranged from 14.6% to 66.5%. Case-control studies reported a prevalence ranging from 16.0% to 25.7% in controls, compared with 26.8% to 96.0% for migraine with aura. The extent of improvement or resolution of migraine headache attack symptoms was variable. In case series, intervention ameliorated migraine headache attack in 13.6% to 92.3% of cases. One single randomized trial did not show any benefit from patent foramen ovale closure. The data overall do not exclude the possibility of a placebo effect for resolving migraine following patent foramen ovale closure.
CONCLUSION: This systematic review demonstrates firstly that migraine headache attack is associated with a higher prevalence of patent foramen ovale than among the general population. Observational data suggest that some improvement of migraine would be observed if the patent foramen ovale were to be closed. A proper assessment of any interventions for patent foramen ovale closure would require further large randomized trials to be conducted given uncertainties from existing trial data.
CONTEXT: The role of percutaneous closure of patent foramen oval (PFO) in patients with cryptogenic stroke has been very controversial for years due to a lack of clear evidence. OBJECTIVE: Systematic review and meta-analysis of the effect of percutaneous PFO closure for secondary prevention of cryptogenic strokes as compared to best medical therapy (BMT). DATA SOURCES: Trials were identified through a literature search until 28 May 2013. STUDY SELECTION: Controlled clinical trials (randomised and non-randomised) comparing percutaneous PFO closure with BMT. DATA EXTRACTION AND SYNTHESIS: Main end point of interest was stroke. A random effects model was used to calculate the pooled relative risks (RR) with 95% CIs. RESULTS: A total of 14 studies (three randomised controlled trials (RCT) and 11 non-randomised observational studies (non-RCT)), and a total of 4335 patients were included for this analysis. There was no significant treatment effect of PFO closure regarding stroke among the RCT (RR 0.66, 95% CI 0.37 to 1.19, p=0.171). However, among non-RCT stroke was reduced (RR 0.37, 95% CI 0.20 to 0.67, p<0.001) after PFO closure. A time-to-event (stroke) analysis, combining all three RCT and the two non-RCT which applied strict multivariate adjustments, showed a borderline significant risk reduction after PFO closure (HR 0.58, 95% CI 0.33 to 0.99, p=0.047). Neither risk of bleeding nor mortality differed significantly between the groups. However, there was a higher incidence of new onset atrial fibrillation in the closure group (RR 3.50, 95% CI 1.47 to 8.35, p=0.005). CONCLUSIONS: Percutaneous closure of PFO in patients with cryptogenic stroke does not appear superior to medical therapy according to currently available randomised data. Furthermore, it is associated with an increased incidence of atrial fibrillation. However, there are signals pointing towards a potential benefit and more research should be strongly encouraged.
BACKGROUND AND PURPOSE: Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. METHODS: A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. RESULTS: Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24-0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91-3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07-0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18-0.98). CONCLUSIONS: Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.
OBJECTIVES: In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO).
BACKGROUND: A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO.
METHODS: We conducted a MEDLINE search with standard search terms to determine eligible studies.
RESULTS: Adjusted incidence rates of RNE were 0.8 (95% confidence interval [CI]: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia.
CONCLUSIONS: Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies.
OBJECTIVES: To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of migraine.
BACKGROUND: In recent years, a potential relationship between, migraine, stroke, and patent foramen ovale (PFO) has emerged.
METHODS: BioMedCentral, Google Scholar, and PubMed from January 2000 to December 2008 were systematically searched for pertinent clinical studies. Secondary sources were also used. Secondary prevention studies of transcatheter closure for patent foramen ovale were required to include at least more than 10 patients followed for more than 6 months. The primary end-point was the rate of cured or significantly improved migraine after percutaneous PFO closure.
RESULTS: After excluding 637 citations, we finally included a total of 11 studies for a total of 1,306 patients. Forty percent of the subjects included suffered from migraine, while most had a previous history of transient ischemic attack/stroke and were investigated retrospectively. Quantitative synthesis showed that complete cure of migraine in 46% (95% C.I.25-67%), while resolution or significant improvement of migraine occurred in 83% (95% C.I. 78-88%) of cases.
CONCLUSIONS: Notwithstanding the limitations inherent in the primary studies, this systematic review suggests that a significant group of subjects with migraine, in particular if treated after a neurological event, may benefit from percutaneous closure of their patent foramen ovale. However, many questions remain unsolved.
Observational studies have shown percutaneous patent foramen ovale (PFO) closure to be a safe means of reducing the frequency and duration of migraine.
OBJECTIVE:
This study evaluated the efficacy and safety of PFO closure in patients with migraine using evidence-based medicine.
METHODS:
The Pubmed (MEDLINE), Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs), cohort studies, and retrospective case series from January 1, 2001, to February 30, 2021. The Jadad scale and R 4.1.0 software were used to assess the quality of the literature and meta-analysis, respectively.
RESULTS:
In total, three randomized controlled trials, one pooled study, and eight retrospective case series including 1,165 participants were included in the meta-analysis. Compared with control intervention in migraine, PFO closure could significantly reduce headache frequency (OR = 1.5698, 95% CI.: 1.0465-2.3548, p=0.0293) and monthly migraine attacks and monthly migraine days (OR = 0.2594, 95% CI.: 0.0790-0.4398, p=0.0048). Subgroup analysis of patients who all completed PFO surgery showed resolution of migraine headache for migraines with aura (OR = 1.5856, 95% CI.: 1.0665-2.3575, p=0.0227).
CONCLUSIONS:
Treatment with PFO closure could reduce the frequency of headaches and monthly migraine days and is an efficient treatment for migraine attacks with aura.
