Objectives: To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs. Setting: A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources: The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. Participants: A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed. Primary and secondary outcome measures: Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up. Data analysis: Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale. Results: Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I ² =40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I ² =72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I ² =59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I ² =91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P _interaction =0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, P _interaction <0.001). Conclusion: Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura. PROSPERO registration number: CRD42016052460 .

Importance Recent epidemiologic and therapeutic advances have transformed understanding of the role of and therapeutic approach to patent foramen ovale (PFO) in ischemic stroke. Patent foramen ovale is likely responsible for approximately 5% of all ischemic strokes and 10% of those occurring in young and middle-aged adults. Observations Randomized clinical trials have demonstrated that, to prevent recurrent ischemic stroke in patients with PFO and an otherwise-cryptogenic index ischemic stroke, PFO closure is superior to antiplatelet medical therapy alone; these trials have provided some evidence that, among medical therapy options, anticoagulants may be more effective than antiplatelet agents. Conclusions and Relevance These new data indicate a need to update classification schemes of causative mechanisms in stroke, developed in an era in which an association between PFO and stroke was viewed as uncertain. We propose a revised general nomenclature and classification framework for PFO-associated stroke and detailed revisions for the 3 major stroke subtyping algorithms in wide use.

Background—: In the era of drug-eluting stents, it is unknown if intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention should be routinely endorsed. This study aimed to determine if IVUS-guided stent implantation is associated with improved outcomes. Methods and Results—: Randomized trials that reported clinical outcomes and compared routine IVUS-guided stent implantation with an angiography-guided approach in the era of drug-eluting stents were included. Summary estimates were constructed primarily using the Peto model. Seven trials with 3192 patients were analyzed. The mean length of the coronary lesions was 32 mm. At a mean of 15 months, routine IVUS-guided percutaneous coronary intervention was associated with a reduction in the risk of major adverse cardiac events (6.5% versus 10.3%; odds ratio, 0.60; 95% confidence interval, 0.46–0.77; P <0.0001), mainly because of reduction in the risk of ischemia-driven target lesion revascularization (4.1% versus 6.6%; odds ratio, 0.60; 95% confidence interval, 0.43–0.84; P =0.003). The risk of cardiovascular mortality (0.5% versus 1.2%; odds ratio, 0.46; 95% confidence interval, 0.21–1.00; P =0.05), and stent thrombosis (0.6% versus 1.3%; odds ratio, 0.49; 95% confidence interval, 0.24–0.99; P =0.04) also appeared to be lower in the IVUS-guided group. Conclusions—: In the era of drug-eluting stents for diffuse coronary lesions, IVUS-guided percutaneous coronary intervention is superior to angiography-guided percutaneous coronary intervention in reducing the risk of major adverse cardiac events. This is primarily because of reduction in the risk of ischemia-driven target lesion revascularization. This analysis also suggests that risk of cardiovascular mortality and stent thrombosis might be lower with an IVUS-guided approach.