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- Magnani, G., et al.
(författare)
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Efficacy and safety of ticagrelor for long-term secondary prevention of atherothrombotic events in relation to renal function: insights from the PEGASUS-TIMI 54 trial
- 2016
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:4, s. 400-408
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We evaluated the relationship of renal function and ischaemic and bleeding risk as well as the efficacy and safety of ticagrelor in stable patients with prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated glomerular filtration rate (eGFR), with <60 mL/min/1.73 m2 pre-specified for analysis of the effect of ticagrelor on the primary efficacy composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE) and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to those without, which remained significant after multivariable adjustment (hazard ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The relative risk reduction in MACE with ticagrelor was similar in those with eGFR <60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. >/=60 (HR 0.88; 95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk in the former group, the absolute risk reduction with ticagrelor was higher: 2.7 vs. 0.63%. Bleeding tended to occur more frequently in patients with renal dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In patients with a history of MI, patients with renal dysfunction are at increased risk of MACE and consequently experience a particularly robust absolute risk reduction with long-term treatment with ticagrelor.
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- Furtado, R. H. M., et al.
(författare)
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Caffeinated Beverage Intake, Dyspnea With Ticagrelor, and Cardiovascular Outcomes: Insights From the PEGASUS-TIMI 54 Trial
- 2020
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. METHODS AND RESULTS: This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI, 0.76-1.10; P= 0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63-0.98; P=0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57-1.70; P=0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56-2.04; P=0.84). CONCLUSIONS: In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias.
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- Sourdis, Ioannis, 1979, et al.
(författare)
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DeSyRe: On-demand adaptive and reconfigurable fault-tolerant SoCs
- 2014
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Ingår i: Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. ; 8405, s. 312-317
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Konferensbidrag (refereegranskat)abstract
- The DeSyRe project builds on-demand adaptive, reliable Systems-on-Chips. In response to the current semiconductor technology trends thatmake chips becoming less reliable, DeSyRe describes a newgeneration of by design reliable systems, at a reduced power and performance cost. This is achieved through the following main contributions. DeSyRe defines a fault-tolerant system architecture built out of unreliable components, rather than aiming at totally fault-free and hence more costly chips. In addition, DeSyRe systems are on-demand adaptive to various types and densities of faults, as well as to other system constraints and application requirements. For leveraging on-demand adaptation/customization and reliability at reduced cost, a new dynamically reconfigurable substrate is designed and combined with runtime system software support. The above define a generic and repeatable design framework, which is applied to two medical SoCs with high reliability constraints and diverse performance and power requirements. One of the main goals of the DeSyRe project is to increase the availability of SoC components in the presence of permanents faults, caused at manufacturing time or due to device aging. A mix of coarse- and fine-grain reconfigurable hardware substrate is designed to isolate and bypass faulty component parts. The flexibility provided by the DeSyRe reconfigurable substrate is exploited at runtime by system optimization heuristics,which decide tomodify component configurationwhen a permanent fault is detected, providing graceful degradation.
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| 6. |
- Sourdis, Ioannis, 1979, et al.
(författare)
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DeSyRe: On-demand system reliability
- 2013
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Ingår i: Microprocessors and Microsystems. - : Elsevier BV. - 0141-9331. ; 37:8, s. 981-1001
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Tidskriftsartikel (refereegranskat)abstract
- The DeSyRe project builds on-demand adaptive and reliable Systems-on-Chips (SoCs). As fabrication technology scales down, chips are becoming less reliable, thereby incurring increased power and performance costs for fault tolerance. To make matters worse, power density is becoming a significant limiting factor in SoC design, in general. In the face of such changes in the technological landscape, current solutions for fault tolerance are expected to introduce excessive overheads in future systems. Moreover, attempting to design and manufacture a totally defect-/fault-free system, would impact heavily, even prohibitively, the design, manufacturing, and testing costs, as well as the system performance and power consumption. In this context, DeSyRe delivers a new generation of systems that are reliable by design at well-balanced power, performance, and design costs. In our attempt to reduce the overheads of fault-tolerance, only a small fraction of the chip is built to be fault-free. This fault-free part is then employed to manage the remaining fault-prone resources of the SoC. The DeSyRe framework is applied to two medical systems with high safety requirements (measured using the IEC 61508 functional safety standard) and tight power and performance constraints.
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| 7. |
- Barbieri, Chiara, et al.
(författare)
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A global analysis of matches and mismatches between human genetic and linguistic histories
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 119:47
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Tidskriftsartikel (refereegranskat)abstract
- Human history is written in both our genes and our languages. The extent to which our biological and linguistic histories are congruent has been the subject of considerable debate, with clear examples of both matches and mismatches. To disentangle the patterns of demographic and cultural transmission, we need a global systematic assessment of matches and mismatches. Here, we assemble a genomic database (GeLaTo, or Genes and Languages Together) specifically curated to investigate genetic and linguistic diversity worldwide. We find that most populations in GeLaTo that speak languages of the same language family (i.e., that descend from the same ancestor language) are also genetically highly similar. However, we also identify nearly 20% mismatches in populations genetically close to linguistically unrelated groups. These mismatches, which occur within the time depth of known linguistic relatedness up to about 10,000 y, are scattered around the world, suggesting that they are a regular outcome in human history. Most mismatches result from populations shifting to the language of a neighboring population that is genetically different because of independent demographic histories. In line with the regularity of such shifts, we find that only half of the language families in GeLaTo are genetically more cohesive than expected under spatial autocorrelations. Moreover, the genetic and linguistic divergence times of population pairs match only rarely, with Indo-European standing out as the family with most matches in our sample. Together, our database and findings pave the way for systematically disentangling demographic and cultural history and for quantifying processes of shifts in language and social identities on a global scale.
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| 8. |
- Harrington, Robert A., et al.
(författare)
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The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
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| 9. |
- Murphy, S. A., et al.
(författare)
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Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome The IMPROVE-IT Trial
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 67:4, s. 353-361
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. OBJECTIVES This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. METHODS All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization >= 30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. RESULTS Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). CONCLUSIONS Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878) (C) 2016 by the American College of Cardiology Foundation.
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