Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Heuristic Search for Defect Tolerant Multiprocessor Arrays

In this paper, new heuristic-search methods and algorithms are presented for enabling highly efficient and adaptive, defect-tolerant multiprocessor arrays. We consider systems where a homogeneous multiprocessor array lies on top of reconfigurable interconnects which allow the pipeline stages of the processors to be connected in all possible configurations. Considering the multiprocessor array partitioned in substitutable units at the granularity of pipeline stages, we employ a variety of heuristic-search methods and algorithms to isolate and replace defective units. The proposed heuristics are designed for off-line execution and aim at minimizing the performance overhead necessarily introduced to the array by the interconnects' latency. An empirical evaluation of the designed algorithms is then carried out, in order to assess the targeted problem and the efficacy of our approach. Our findings indicate this to be a NP-complete computational problem, however, our heuristic-search methods can achieve 100% accuracy in finding the optimal solution among 10^19 possible candidates within 2.5 seconds. Alternatively, they can provide near-optimal solutions at an accuracy which consistently exceeds 70% (compared to the optimal solution) in only 10^-4 seconds.Computer EngineeringComputer Science and EngineeringElectrical Engineering, Mathematics and Computer Scienc

Runtime Management of Adaptive MPSoCs for Graceful Degradation

In this paper we propose optimization algorithms for the runtime management of gracefully degradable adaptive MPSoCs. Assuring the reliability of all hardware components in a system becomes increasingly difficult. On top of the growing defect densities and rising complexity of conventional testing, wear-out effects may reduce the availability of on-chip resources during system lifetime. However, adaptability of modern MPSoCs can provide the means for permanent fault tolerance and graceful degradation via runtime system management. We have developed custom heuristics as well as tailored existing optimization techniques (simulated annealing and genetic algorithm), to deliver a fast and efficient response to unpredictable loss of system resources. We have emulated the resulting runtime manager on the Intel Single-Chip Cloud Computer (SCC), an experimental chip multiprocessor developed by Intel Labs. Comparison of the different algorithms in terms of solution quality and response time, and the scaling of their response time with the size of problem input, indicate that our custom heuristics are faster by at least one order of magnitude, but simulated annealing and genetic algorithm are more consistent in dealing with constraints to the allowed solutions, e.g. limited system reconfiguration time. All algorithms scale well, since their response time, in almost every case, grows sub-linearly with respect to the input size

Heuristic Search for Adaptive, Defect-Tolerant Multiprocessor Arrays

In this article, new heuristic-search methods and algorithms are presented for enabling highly efficient and adaptive, defect-tolerant multiprocessor arrays. We consider systems where a homogeneous multiprocessor array lies on top of reconfigurable interconnects which allow the pipeline stages of the processors to be connected in all possible configurations. Considering the multiprocessor array partitioned in substitutable units at the granularity of pipeline stages, we employ a variety of heuristic-search methods and algorithms to isolate and replace defective units. The proposed heuristics are designed for off-line execution and aim at minimizing the performance overhead necessarily introduced to the array by the interconnects\u27 latency. An empirical evaluation of the designed algorithms is then carried out, in order to assess the targeted problem and the efficacy of our approach. Our findings indicate this to be a NP-complete computational problem, however, our heuristic-search methods can achieve, for the problem sizes we exhaustively searched, 100% accuracy in finding the optimal solution among 10(19) possible candidates within 2.5 seconds. Alternatively, they can provide near-optimal solutions at an accuracy which consistently exceeds 70% (compared to the optimal solution) in only 10(-4) seconds

QT interval extracted from 30-minute short resting Holter ECG recordings predicts mortality in heart failure

Background: Prolonged repolarization duration is a significant total mortality (TM) predictor in post-myocardial infarction patients. Aim: We examined the clinical significance of QT interval that was extracted from a Short Resting Holter ECG (SRH ECG – 30-min duration) as a TM predictor in heart failure (HF) patients. Methods: One hundred forty-five HF patients (male = 84%, mean age = 64 ± 12 years, mean LVEF = 33 ± 10%) underwent an SRH ECG recording for 30 min. These high-resolution ECG signals were analyzed and the QT interval was calculated and corrected according to the Fridericia formula. After 42.1 months, 26 patients died. Results: Univariate analysis for Deceased and Living groups: QTc:455 ± 33 ms vs 441 ± 32 ms (p = 0.04), LVEF:32 ± 10% vs 34 ± 9% (p < 0.5), Mean Heart Rate: 73 ± 11 bpm vs 69 ± 12 bpm (p = 0.2), SDNN/HRV: 45 ± 42 ms vs 41 ± 29 ms (p = 0.4), QRS: 123 ± 26 ms vs 119 ± 29 ms (p = 0.5). Multivariate Cox regression analysis with model adjusted for QTc, Mean Heart Rate, LVEF, QRS, revealed that QTc-Fridericia interval was an independent TM predictor (H.R.:1.017, 95% C.I.: 1.003–1.030, p = 0.01). The cut-off point of 490 ms (90th percentile) in the same model presented HR: 2.9 for TM (95%C.I.: 1.066–7.882, p = 0.03). Kaplan Meier curves depicted a clear difference in survival between the two patients' groups (QTc Group≥490 ms vs QTc Group <490 ms). The curve diverge was important (log-rank, p = 0.02). Conclusion: A fast risk stratification approach with SRH ECG recording is an efficient method for flash evaluation of mortality risk in HF patients. © 2022 Elsevier Inc

Ticagrelor versus clopidogrel in patients with STEMI treated with thrombolysis: The MIRTOS trial

Aims: We aimed to demonstrate whether coronary microvascular function is improved after ticagrelor administration compared to clopidogrel administration in STEMI subjects undergoing thrombolysis. Methods and results: MIRTOS is a multicentre study of ticagrelor versus clopidogrel in STEMI subjects treated with fibrinolysis. We enrolled 335 patients <75 years old with STEMI eligible for thrombolysis, of whom 167 were randomised to receive clopidogrel and 168 to receive ticagrelor together with thrombolysis. Primary outcome was the difference in post-PCI corrected TIMI frame count (CTFC). All clinical events were recorded in a three-month follow-up period. From the 335 patients who were randomised, 259 underwent PCI (129 clopidogrel and 130 ticagrelor) and 154 angiographies were analysable for the study primary endpoint. No significant difference was found between the clopidogrel (n=85) and ticagrelor (n=69) groups for CTFC (24.33±17.35 vs 28.33±17.59, p=0.10). No significant differences were observed in MACE and major bleeding events between randomisation groups (OR 2.0, 95% CI: 0.18-22.2, p=0.99). Conclusions: Thrombolysis with ticagrelor in patients <75 years old was not able to demonstrate superiority compared to clopidogrel in terms of microvascular injury, while there was no difference between the two groups in MACE and major bleeding events. Trial Registration. ClinicalTrials.gov Identifier: NCT02429271. EudraCT Number 2014-004082-25. © Europa Digital & Publishing 2021. All rights reserved

Patients with Acute Coronary Syndrome are at High Risk Prior to the Event and Lipid Management is Underachieved Pre- and Post-Hospitalization

Background: Current European Guidelines suggest the use of cardiovascular risk categories and also recommend using high-intensity statins for patients with acute coronary syndromes (ACS). Objective: We examined the risk of ACS patients prior to the event, as well as the overall use and intensity of statins. Methods: We enrolled 687 ACS patients (mean age 63 years, 78% males). Low-density lipoprotein cholesterol (LDL-C) levels upon admission were used to assess attainment of LDL-C targets. Patients were categorized as very high, high, moderate and low risk based on their prior to admission cardiovascular (CV) risk. We examined statin use and dosage intensity among patients discharged from the hospital. Patients were followed for a median period of 189 days. Results: The majority of the patients (n=371, 54%) were at very high CV risk prior to admission, while 101 patients were at high risk (15%), 147 (21%) moderate risk and 68 (10%) low risk. Interestingly, LDL-C target attainment decreased as the risk increased (p<0.001). The majority (96%) of patients received statins at discharge; however, most of them (60.4%) received low/moderate intensity statins and just 35.9% received the suggested by the Guidelines high-intensity dose of statins. At follow-up, the rate of patients at high-intensity dose of statins remained similar (34.8%); 6% received no statins at all at follow-up. Conclusion: According to our study, the majority of ACS patients are already at high risk prior to their admission. Further, LDL-C targets are underachieved prior to the event and high-intensity statins are underutilized in ACS patients at, and post-discharge