New Oral Anticoagulants are Not Superior to Warfarin in Secondary Prevention of Stroke or Transient Ischemic Attacks, but Lower the Risk of Intracranial Bleeding: Insights from a Meta-Analysis and Indirect Treatment Comparisons

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA). METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan and Stata software were used for direct and indirect comparisons, respectively. RESULTS: In patients with AF and previous stroke or TIA, effects of NOACs were not statistically different from that of warfarin, in reduction of stroke (Odds Ratio [OR] 0.86, 95% confidence interval [CI] 0.73- 1.01), disabling and fatal stroke (OR 0.85, 95% CI 0.71-1.04), and all-cause mortality (OR 0.90, 95% CI 0.79 -1.02). Randomization to NOACs was associated with a significantly lower risk of intracranial bleeding (OR 0.42, 95% CI 0.25-0.70). There were no major differences in efficacy between apixaban, dabigatran (110 mg BID and 150 mg BID) and rivaroxaban. Major bleeding was significantly lower with apixaban and dabigatran (110 mg BID) compared with dabigatran (150 mg BID) and rivaroxaban. CONCLUSION: NOACs may not be more effective than warfarin in the secondary prevention of ischemic stroke in patients with a prior history of cerebrovascular ischemia, but have a lower risk of intracranial bleeding

Distinguishing between flaring and nonflaring active regions

Context. Large-scale solar eruptions significantly affect space weather and damage space-based human infrastructures. It is necessary to predict large-scale solar eruptions; it will enable us to protect the vulnerable infrastructures of our modern society. Aims. We investigate the difference between flaring and nonflaring active regions. We also investigate whether it is possible to forecast a solar flare. Methods. We used photospheric vector magnetogram data from the Solar Dynamic Observatory’s Helioseismic Magnetic Imager to study the time evolution of photospheric magnetic parameters on the solar surface. We built a database of flaring and nonflaring active regions observed on the solar surface from 2010 to 2017. We trained a machine-learning algorithm with the time evolution of these active region parameters. Finally, we estimated the performance obtained from the machine-learning algorithm. Results. The strength of some magnetic parameters such as the total unsigned magnetic flux, the total unsigned magnetic helicity, the total unsigned vertical current, and the total photospheric magnetic energy density in flaring active regions are much higher than those of the non-flaring regions. These magnetic parameters in a flaring active region evolve fast and are complex. We are able to obtain a good forecasting capability with a relatively high value of true skill statistic. We also find that time evolution of the total unsigned magnetic helicity and the total unsigned magnetic flux provides a very high ability of distinguishing flaring and nonflaring active regions. Conclusions. We can distinguish a flaring active region from a nonflaring region with good accuracy. We confirm that there is no single common parameter that can distinguish all flaring active regions from the nonflaring regions. However, the time evolution of the top two magnetic parameters, the total unsigned magnetic flux and the total unsigned magnetic helicity, have a very high distinguishing capability

Two-year Outcomes of Bioresorbable Vascular Scaffold Versus Drug-Eluting Stents in Coronary Artery Disease: A Meta-analysis

BACKGROUND: Data regarding long-term clinical outcomes with everolimus-eluting bioresorbable vascular scaffold (BVS) versus second-generation drug-eluting stents (DES) are scarce. METHODS: We searched online databases until October 2016 for studies comparing BVS versus DES reporting outcomes at 2 years of follow-up. We performed a meta-analysis comparing BVS with DES across the spectrum of coronary artery disease (CAD). Random effects model OR was calculated for outcomes of interest including device-oriented composite events (DOCE; defined as composite of cardiac mortality, target vessel myocardial infarction (TV-MI), and ischaemia-driven target lesion revascularisation (TLR)), all-cause mortality, definite stent thrombosis, TV-MI and TLR. RESULTS: A total of 2360 patients enrolled in five studies met criteria for inclusion in this analysis. At 2 years, BVS was associated with higher rates of DOCE (6.9% vs 4.5%, OR=1.53; 95% CI 1.06 to 2.23; p=0.02), absolute risk increase (ARI) 2.4%, relative risk increase (RRI) 53%, TV-MI (4% vs 1.8%, OR=1.94; 95% CI 1.02 to 3.67; p=0.04), ARI 2.2%, RRI 122% and definite stent thrombosis (2.1% vs 0.6%, OR=3.39; 95% CI 1.46 to 7.88; p=0.005), ARI 1.5%, RRI 250% compared with DES. No differences in all-cause mortality (OR=0.86; 95% CI 0.26 to 2.81; p=0.80) and TLR (OR=1.44; 95% CI 0.81 to 2.54; p=0.21) were observed between both groups. CONCLUSIONS: BVS may be associated with worse long-term clinical outcomes compared with DES. Randomised clinical trials are encouraged to expeditiously report long-term safety and efficacy outcomes and identify predictors of adverse events with BVS compared with DES

New Oral Anticoagulants and the Risk of Intracranial Hemorrhage Traditional and Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials of New Oral Anticoagulants in Atrial Fibrillation

IMPORTANCE Randomized studies have shown a decreased risk of intracranial hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). However, it is unclear whether the magnitude of benefit is similar for all NOACs currently available. OBJECTIVE To perform a systematic review and meta-analysis to quantitatively assess the rates of ICH within the framework of both conventional and Bayesian statistics. DATA SOURCES The MEDLINE, CENTRAL, CINAHL, and EBSCO databases, supplemented with conference abstracts, were searched up to December 1, 2012, with no language restriction. STUDY SELECTION Randomized trials comparing NOACs vs a comparator and reporting on ICH events. DATA EXTRACTION AND SYNTHESIS The NOACs were pooled to perform a comparison with all comparators and among themselves in both traditional frequentist and Bayesian random-effects models using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled odds ratios and associated 95% confidence intervals as well as numbers needed to treat and 95% credible intervals for the Bayesian analysis. MAIN OUTCOMES AND MEASURES Intracranial hemorrhage events associated with NOACs in comparison with comparators, expressed as odds ratios. RESULTS Six studies (1 administering dabigatran etexilate mesylate, 2 administering rivaroxaban, and 3 administering apixaban) enrolling a total of 57 491 patients were included for analysis. The NOACs significantly reduced the risk of ICH against all comparators (odds ratio = 0.49; 95% CI, 0.36-0.65). Each of the 3 drugs reduced the risk of ICH, with Bayesian indirect comparison analysis not revealing a significant credible difference between the specific medications. CONCLUSIONS AND RELEVANCE Novel oral anticoagulants are uniformly associated with an overall reduced risk of ICH when used for stroke prevention in atrial fibrillation. Any of the currently available NOACs can be considered first line for patients at high risk for ICH