Assessment of Two Advanced Aluminium-Based Metal Matrix Composites for Application to High Energy Physics Detectors.

The Outer Tracker of the Compact Muon Solenoid (CMS), one of the large experiments at the CERN Large Hadron Collider, will consist of about 13,200 modules, each built up of two silicon sensors. The modules and support structures include thousands of parts that contribute to positioning and cooling the sensors during operation at -30 °C. These parts should be low mass while featuring high thermal conductivity, stiffness and strength. Their thermal expansion coefficient should match that of silicon to avoid deformations during cooling cycles. Due to their unique thermal and mechanical properties, aluminium-carbon fibre (Al/Cf) Metal Matrix Composites are the material of choice to produce such light and stable thermal management components for High Energy Physics detectors. For the CMS Outer Tracker, about 500,000 cm3 of Al/Cf raw material will be required to be produced through a reliable process to guarantee consistent properties throughout parts manufacturing. Two Al/Cf production routes are currently considered: liquid casting by gas-pressure infiltration and a powder metallurgy process based on continuous semi-liquid phase sintering. The dimensional stability of the resulting material is of paramount importance. Irreversible change of shape may be induced by moisture adsorption and the onset of galvanic corrosion at the discontinuous interfaces between Cf and Al. This paper presents the results of an extensive investigation through Computed Microtomography, direct microscopical investigations, analysis of the interfaces and metrology measurements aimed at comparing and interpreting the response to different environments of the respective products. The results obtained confirm the suitability of the two investigated Al/Cf MMCs for application to components of the CMS Outer Tracker, requiring tight geometrical control and microstructural stability over time. However, for PM parts sintered through the semi-liquid phase process, a multilayered protective noble metal coating is necessary the make them impervious to moisture, allowing dimensional stability to be guaranteed and the onset of corrosion phenomena to be avoided, while the product obtained by gas-pressure infiltration has shown less sensitive even to extreme temperature-humidity cycles and may be used uncoated.

Seguimiento a largo plazo de enfermos con fibrilación auricular del estudio NASPEAF. Control prospectivo de otros tratamientos antiplaquetarios / Long-term follow-up of atrial fibrillation patients in the NASPEAF study. Prospective evaluation of different antiplatelet treatments

Introducción y objetivos. En el estudio NASPEAF, el tratamiento combinado anticoagulante más antiplaquetario fue más beneficioso que la anticoagulación sola en los enfermos con fibrilación auricular. Presentamos el seguimiento a largo plazo de los enfermos de este estudio, controlando de forma prospectiva otros tratamientos antiplaquetarios alternativos. Métodos. Se ha incluido en este análisis a 574 pacientes con fibrilación auricular. El tratamiento anticoagulante estándar (INR 2,0-3,0) se utilizó como control frente a la anticoagulación (INR 1,9-2,5) más triflusal 600 mg/día, triflusal 300 mg/día o ácido acetilsalicílico 100 mg/día. El evento primario fue ictus isquémico/hemorrágico, accidente isquémico sistémico/coronario y muerte cardiovascular. La media de tiempo de seguimiento fue 4,92 años. Resultados. El seguimiento a largo plazo confirmó el beneficio significativo del tratamiento combinado anticoagulante más triflusal 600 mg/día frente a la anticoagulación sola (hazard ratio [HR] = 0,33; intervalo de confianza [IC] del 95%, 0,14-0,80; p = 0,014). Se observó una mayor tasa de accidentes isquémicos durante el uso de triflusal 300 mg/día (p = 0,031) y de hemorragias severas con ácido acetilsalicílico 100 mg/día (p = 0,008). El valor medio del INR fue muy similar en los tres grupos que recibieron tratamiento combinado. La tasa de hemorragias no gástricas severas durante el tratamiento combinado con triflusal fue muy baja (0,3% pacientes/año). Conclusiones. El seguimiento a largo plazo ha confirmado el beneficio del tratamiento antitrombótico combinado con triflusal 600 mg/día frente a la monoterapia anticoagulante. Los resultados del tratamiento combinado con triflusal 300 mg/día y ácido acetilsalicílico 100 mg/ día deben considerarse preliminares, por ser grupos de pequeño tamaño y no haber sido aleatorizados (AU)

Introduction and objectives. In the NASPEAF (National Study for Prevention of Embolism in Atrial Fibrillation) trial, combination therapy with an anticoagulant and an antiplatelet was more effective than anticoagulation alone in patients with atrial fibrillation. We report long-term follow-up in these patients, including prospective evaluation of different antiplatelet therapies. Methods. This analysis included 574 atrial fibrillation patients. Standard anticoagulation (international normalized ratio [INR], 2.0-3.0) was used as control therapy to compare with anticoagulation (INR, 1.9-2.5) plus either triflusal at 600 mg/d, triflusal at 300 mg/d, or aspirin at 100 mg/d. The primary endpoint was ischemic or hemorrhagic stroke, a systemic or coronary ischemic event, or cardiovascular death. The mean follow-up was 4.92 years. Results. Long-term follow-up confirmed that combination therapy with an anticoagulant plus triflusal at 600 mg/day gave significantly better results than anticoagulation alone (hazard ratio [HR]=0.33; 95% confidence interval [CI], 0.14-0.80; P=.014). There was a significantly higher incidence of ischemic events with triflusal at 300 mg/day (P=.031) and of severe bleeding events with aspirin at 100 mg/d (P=.008). The mean INR was similar in the three combination therapy groups. The incidence of severe nongastric bleeding during combination therapy with triflusal was very low (0.3% of patients/year). Conclusions. Long-term follow-up confirmed that combination antithrombotic therapy with triflusal at 600 mg/d gave significantly better results than anticoagulant monotherapy. The results obtained with combination therapy with triflusal at 300 mg/d and with aspirin at 100 mg/d should be considered provisional because the treatment groups were small and treatment was not randomly assigned (AU)

Long-term follow-up of atrial fibrillation patients in the NASPEAF study. Prospective evaluation of different antiplatelet treatments.

INTRODUCTION AND OBJECTIVES: In the NASPEAF (National Study for Prevention of Embolism in Atrial Fibrillation) trial, combination therapy with an anticoagulant and an antiplatelet was more effective than anticoagulation alone in patients with atrial fibrillation. We report long-term follow-up in these patients, including prospective evaluation of different antiplatelet therapies. METHODS: This analysis included 574 atrial fibrillation patients. Standard anticoagulation (international normalized ratio [INR] 2.0-3.0) was used as control therapy to compare with anticoagulation (INR 1.9-2.5) plus either triflusal at 600 mg/day, triflusal at 300 mg/day or aspirin at 100 mg/day. The primary endpoint was ischemic or hemorrhagic stroke, a systemic or coronary ischemic event, or cardiovascular death. The mean follow-up was 4.92 years. RESULTS: Long-term follow-up confirmed that combination therapy with an anticoagulant plus triflusal at 600 mg/day gave significantly better results than anticoagulation alone (hazard ratio [HR]=0.33; 95% confidence interval [CI], 0.14-0.80; P=.014). There was a significantly higher incidence of ischemic events with triflusal at 300 mg/day (P=.031) and of severe bleeding events with aspirin at 100 mg/day (P=.008). The mean INR was similar in the three combination therapy groups. The incidence of severe nongastric bleeding during combination therapy with triflusal was very low (0.3% of patients/year). CONCLUSIONS: Long-term follow-up confirmed that combination antithrombotic therapy with triflusal at 600 mg/day gave significantly better results than anticoagulant monotherapy. The results obtained with combination therapy with triflusal at 300 mg/day and with aspirin at 100 mg/day should be considered provisional because the treatment groups were small and treatment was not randomly assigned.

Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators.

BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. METHODS: This is an analysis of the Atrial Fibrillation Investigators database, which contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure. Outcomes included ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding requiring hospitalization, transfusion, or surgery), and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death). RESULTS: The analysis included 8932 patients and 17 685 years of observation from 12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to 1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to 0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to 0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome. Compared with placebo, the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged (P=0.01). CONCLUSIONS: As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC. Because stroke risk increases with age, the absolute benefit of OAC increases as patients get older.

La nueva cascada de la coagulación y su posible influencia en el difícil equilibrio entre trombosis y hemorragia / The new coagulation cascade and its possible influence on the delicate balance between thrombosis and hemorrhage

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Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial.

AIMS: Atrial fibrillation patients with prior embolism have a high risk of vascular events in spite of anticoagulant therapy and elderly patients carry an additional risk. We analysed and compared vascular events-rate between older and younger than 75 years atrial fibrillation patients randomized to anticoagulant-alone or combined antiplatelet plus moderate-level anticoagulant therapy. METHODS AND RESULTS: A total of 967 patients stratified by age and the history of prior embolism were randomized to therapeutic doses of anticoagulant-alone or combined antithrombotic therapy. Primary events were fatal and non-fatal ischaemic or haemorrhagic stroke/transient ischaemic attack, systemic embolism and myocardial infarction, sudden death and death from bleeding. The elderly, compared with the younger patients, had higher event-rate [hazard ratio 2.31 (95% confidence interval 1.37-3.90), P < 0.003]. The elderly suffered higher severe bleeding event-rate during anticoagulant therapy. The combined, compared with the anticoagulant therapy, reduced the vascular events-rate in the elderly (P = 0.012) and caused less intracranial haemorrhages and less bleeding mortality, although more non-fatal gastric bleeding. CONCLUSION: The elderly with AF had a higher event-rate than the younger patients. A higher severe bleeding event-rate was also registered in elderly patients receiving anticoagulant therapy. Combined, compared with anticoagulant therapy, significantly reduced vascular events and bleeding mortality in elderly patients.

Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial.

AIMS: The randomized NASPEAF study included non-valvular with prior embolism and mitral stenosis patients in the same group. This is a sub-study to specially focus on the antithrombotic therapy in mitral stenosis. METHODS AND RESULTS: We analysed 311 patients with mitral stenosis, compared with 175 non-valvular atrial fibrillation patients with prior embolism, stratified by a history of previous embolism and assigned to anticoagulant therapy [target international normalized ratio (INR) = 2.0-3.0] or combined antiplatelet plus moderate intensity anticoagulant therapy. Median follow-up was 2.9 years. Outcomes were fatal and non-fatal embolism, stroke and myocardial infarction, sudden death, and death from bleeding. Combined therapy in mitral stenosis patients, compared with anticoagulant alone therapy, reduced the risk of vascular events by 58.3%. During equal therapy, the outcome annual rates were essentially the same in non-valvular and valvular patients [hazard ratio 0.90 (95% confidence interval 0.37-2.16), P = 0.81]. During anticoagulant alone therapy, the annual event rate in mitral stenosis patients without prior embolism was low (2.5%) and it was very high in patients with prior embolism (6.6%). CONCLUSION: Combined therapy was effective in mitral stenosis patients. Prior embolism patients are not efficiently protected with anticoagulant alone therapy for an INR of 2.0-3.0.

Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.

OBJECTIVES: This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. BACKGROUND: Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated. METHODS: We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism. RESULTS: Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy. CONCLUSIONS: The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.