Impact of Askling L-PROTOCOL on Biceps Femoris Architecture, Hamstring Flexibility and Sprint Performance.

Eccentric training has been shown to be important for hamstring strain injuries rehabilitation and prevention. The Askling L-PROTOCOL (L-P), comprising three exercises aimed at eccentric training and hamstring lengthening, was shown to improve this injuries recovery and relapse times in comparison with other traditional exercise-based protocols. However, the causes of these results remain unclear. This study looks at the impact of an 8-week L-P followed by 4 weeks of detraining on the architecture of the biceps femoris long head, hamstring flexibility and sprint performance. Twenty-eight healthy individuals were divided into two groups: an experimental group, which carried out the L-P, and a control group with no training. Muscle architecture was measured using 2D ultrasound, hamstring flexibility using goniometry and sprint performance using sports radar equipment before (M1) and after (M2) the training period and after detraining (M3). No significant changes were observed between M1 and M2 in the experimental group with regard to fascicle length (t=- 0.79, P>0.05), theoretical maximum speed (t=- 1.43, P>0.05), horizontal force (t=0.09, P>0.05), force application during sprint running (t=- 0.09, P>0.05) and horizontal power (t=- 0.97, P>0.05), but, however, changes were observed in hamstring flexibility (t=- 4.42, d=0.98, P<0.001) returning to pre-training values after detraining period (t=- 1.11, P>0.05). L-P has been shown to be an eccentric protocol of moderate intensity and easy implementation that could be interesting to include throughout a sports season.

Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Effect of concomitant antiplatelet therapy in patients with nonvalvular atrial fibrillation initiating non-vitamin K antagonists.

BACKGROUND: Antiplatelet therapy (APT) use in combination with oral anticoagulation is common among patients with atrial fibrillation, but there is scarce information regarding its effect on outcomes in patients on non-vitamin K antagonist oral anticoagulants (NOAC). We aimed to evaluate the safety and efficacy of APT use in a 'real-world' cohort of nonvalvular atrial fibrillation (NVAF) patients initiating NOAC. DESIGN: We conducted a retrospective multicentre study including 2361 consecutive NVAF patients initiating NOAC between January 2013 and December 2016. Patients with an acute ischaemic event within the last 12 months (acute coronary syndrome, stroke or revascularization) were excluded. Patients were followed up, and all clinical events were recorded at 3 months. The primary outcome of the study was major bleeding, and the secondary outcomes were stroke, nonfatal myocardial infarction, intracranial bleeding and death. RESULTS: One hundred forty-five (6.1%) patients received concomitant APT, and aspirin was the more common (79%). At 3 months, 25 (1.1%) patients had major bleeding, 8 (0.3%) had nonfatal myocardial infarction, 7 (0.3%) had ischaemic stroke, and 40 (1.7%) died. After multivariate adjustment, concomitant APT was associated with higher risk for major bleeding (HR = 3.62, 95% CI 1.32-9.89; P = .012), but was not associated with a higher risk of other clinical outcomes. CONCLUSIONS: Concomitant APT use is uncommon among these patients and does not seem to be associated with lower rates of ischaemic events or death. However, there are signals for an increased risk of bleeding, which reinforces current guideline recommendations.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

BACKGROUND: Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. MATERIAL AND METHODS: This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. RESULTS: During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). CONCLUSIONS: Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis.

Major bleeding risk prediction using Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations in acute coronary syndrome.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate more accurately than the Modification of Diet in Renal Disease (MDRD) Study equation. Our aim was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for major bleeding (MB) more accurately than the MDRD Study equation in patients with non-ST-segment elevation acute coronary syndromes (ACS). MATERIALS AND METHODS: Three hundred and fifty consecutive subjects with non-ST-segment elevation ACS (68 ± 12 years, 70% male) were studied. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. The primary endpoint was the occurrence of MB during the follow-up, which was defined according to the Bleeding Academic Research Consortium Definition criteria as bleeding types 3-5. RESULTS: During the median follow-up of 589 days (interquartile range, 390-986), 27 patients had MB (0.04% events per person year). Patients with MB had worse kidney function parameters, regardless of the estimating equation used (P < 0.001). After multivariate Cox regression adjustment, both CysC-based CKD-EPI equations were independent predictors of MB (CKD-EPI(creatinine-cystatin) C per mL/min/1.73 m(2), HR = 0.973 (95%CI 0.955-0.991; P = 0.003) and CKD-EPI(cystatin) C per mL/min/1.73 m(2), HR = 0.976 (95%CI 0.976-0.992; P = 0.003), while the CKD-EPI(creatinine) and MDRD equations did not achieve statistical significance. Both CKD-EPI(creatine-cystatin) C and CKD-EPI(cystatin) C were associated with a significant improvement in MB risk reclassification. CONCLUSIONS: In this cohort of non-ST-segment elevation ACS patients with relatively preserved renal function, both CysC-based CKD-EPI equations improved ability to predict risk for MB and were superior to other equations for this application.

Aortic valve stenosis planimetry by means of three-dimensional transesophageal echocardiography in the real clinical setting: feasibility, reliability and systematic deviations.

AIMS: To assess the feasibility and reliability of aortic valve area (AVA) planimetry by means of three-dimensional transesophageal echocardiography (3DTEE) as compared with the transthoracic echocardiogram (TTE) calculation of AVA, to determine the systematic deviations between measurements, and to describe the distribution of mean systolic in relation with 3DTEE anatomical AVA. METHODS AND RESULTS: Three hundred seven patients with aortic valve stenosis (AVS) underwent both TTE and 3DTEE for AVA measurement by means of the continuity equation and direct anatomical planimetry, respectively. AVA planimetry was achieved in 282 (91.9%) of patients. Severity of the aortic valve calcification was independently associated with a poorer performance of planimetry. Intraclass correlation coefficient yielded a 0.848 (95% CI: 0.807-0.879) value. 3DTEE rendered a mild constant underestimation of AVA in comparison with TTE. Severe aortic stenosis according to the area criterion (<1 cm(2) ) despite mean systolic gradient below 40 mm Hg was detected in 37.6% of the study population, and in 33.7% of the subset of patients with preserved left ventricular ejection fraction. CONCLUSIONS: Reliability of AVA planimetry by 3DTEE in comparison with the calculation by TTE is good, but 3DTEE underestimates slightly the measurement. Feasibility of the technique is good but independently affected by valvular calcification. Inconsistent classification of AVS severity as graded by AVA or mean systolic gradient is observed in the overall population and in patients with preserved systolic function.

Comparison of risk prediction with the CKD-EPI and MDRD equations in acute decompensated heart failure.

BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively). CONCLUSIONS: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification.

Silencing of δ-aminolevulinic acid dehydratase via virus induced gene silencing promotes callose deposition in plant phloem.

The δ-aminolevulinic acid dehydratase (ALAD) enzyme is an intermediate in the biosynthetic pathway of tetrapyrroles. It combines two δ-aminolevulinic acid (δ-ALA) molecules to form the pyrrole, porphobilinogen, an important precursor for plant pigments involved in photosynthesis, respiration, light-sensing, and nutrient uptake. Our recent efforts showed that, in citrus, silencing of ALAD gene via Citrus tristeza virus-induced gene silencing, caused yellow spots and necrosis in leaves and in developing new shoots. Silencing of ALAD gene reduced leaf pigments and altered leaf metabolites. Moreover, total phenolic content, H2O2, and reactive oxygen species (ROS) increased, indicating that silencing of ALAD induced severe stress. Herein, we hypothesized that conditions including lower sucrose, elevated ROS, alteration of microRNA involved in RNAi regulatory protein Argonaute 1 (AGO1) and ROS lead to higher deposition of callose in phloem tissues. Using aniline blue staining and gene expression analysis of callose synthases, we showed significant deposition of callose in ALAD-silenced citrus.

Large fetal goiter due to placental passage of maternal antithyroperoxidase antibodies.

We report a case of fetal goiter in a pregnant woman with Graves-Basedow disease. It was diagnosed in the third trimester by a routine ultrasound, and the cordocentesis verified increased levels of thyroxine (T4) and increased autoantibodies (antithyroperoxidase antibodies) that were also increased in maternal blood. Fetal goiter got smaller on the follow-up scans, and the newborn presented hypothyroidism. Current notions on the diagnosis and management of fetal goiter are briefly discussed.

Plant Functional Genomics in A Few Days: Laser-Assisted Delivery of Double-Stranded RNA to Higher Plants.

The technology of transgenic plants is challenging and time consuming, especially for higher plants and trees such as citrus. Double-stranded RNA (dsRNA) delivery via a plant virus is an alternative method to create transgenic plants by suppressing the expression of plant endogenous genes. Citrus tristeza virus-based vector has been constructed specifically for use in citrus trees. However, this is time-consuming, as it can take up to nine months to produce the desired phenotype. Here we describe a much faster method for the study of gene function in citrus trees. In the current study, we used laser light for the delivery of dsRNA to citrus leaves. We targeted the endogenous reporter gene phytoene desaturase (PDS) and obtained the classical phenotype (leaf bleaching) in only three days after the laser-assisted delivery. Interestingly, the phenotype response was systemic, which indicates the movement of dsRNA and/or ssRNA within the plants. In addition, dsRNAs were taken up by phloem cells and the bleaching phenotype was clear around the main veins. In conclusion, the delivery of dsRNA to plants through laser treatment may provide a fast and more specific tool to study the gene function in higher plants and trees.

Development of Europium-Sensitized Fluorescence-Based Method for Sensitive Detection of Oxytetracycline in Citrus Tissues.

Antimicrobial compounds have been successfully used to control many plant and animal diseases. Recently, oxytetracycline (OTC) and streptomycin have been approved for the treatment of Huanglongbing in citrus. Since the application of OTC is under strict regulations, several methods have been developed to determine and monitor its levels in the environment including high-performance liquid chromatography, ELISA, colorimetric, and fluorometric assays. In this study, we developed a fluorometric method for the determination of OTC in plant tissues based on its complexation with europium. Our preliminary trials showed that phenols and flavonoids interfere with the europium assay by reacting with the sensitizing reagent, cetyltrimethylammonium chloride. Consequently, we used the 60 mg hydrophilic-lipophilic balanced (HLB) cartridges to purify the OTC from the plant matrix. The recovery of OTC from spiked leaf samples was 75 ± 7.6%. Using the 500 mg HLB, we were able to detect 0.3 ppm OTC in the final sample extract, which corresponds to 3 µg g-1 fresh weight (FWT). The developed method was successfully used to measure the level of OTC in leaves obtained from trunk-injected trees. The results obtained by the europium method were similar to those obtained using the ELISA assay. We also tested the cross-reactivity of OTC metabolites with the europium method. The 4-epi-OTC showed a high cross-reactivity (50.0 ± 3.6%) with europium assay, whereas α-apo-OTC and ß-apo-OTC showed small cross-reactivity. We showed that the europium-sensitized fluorescence-based method can be successfully used to assess OTC in citrus plant tissues after a cleanup step. Our results showed that this method was sensitive, reproducible, and can be used to analyze many samples simultaneously.

Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI Registry.

BACKGROUND: The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. METHODS: Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. RESULTS: After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. CONCLUSIONS: In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

[Incidence of inflammatory bowel disease in the health area of Navalmoral de la Mata (Caceres, Spain) between 2000 and 2009]. / Incidencia de enfermedad inflamatoria intestinal en el área de salud de Navalmoral de la Mata (Cáceres, España) entre 2000 y 2009.

OBJECTIVES: To determine whether the incidence of inflammatory bowel disease (IBD) has changed in our area and whether it has been influenced by the growing immigrant population. POPULATION AND METHODS: From 2000 to 2009, a prospective population-based study was conducted in the population aged over 15 years old and was compared with a study carried out from 1994 to 1998 in the health area of Campo Arañuelo. The distribution of Crohn's disease (CD), ulcerative colitis (UC) and age and sex were analyzed and compared with European rates for the standard population, both for the total population and for the local population. RESULTS: From 2000 to 2009, IBD was diagnosed in 73 patients (36 men and 37 women). CD was diagnosed in 25 patients (34.2%), UC in 46 (63.0%) and there were two cases (2.8%) of indeterminate colitis (IC), which were excluded from the analysis. The mean annual incidence of CD was 5.70 per 100,000 inhabitants (5.79 in men and 5.60 in women). The annual incidence of UC was 11.47 per 100,000 inhabitants (10.79 in men and 12.17 in women). The incidence of UC was significantly higher than that of CD. The UC/CD ratio was 1.87. The mean age of patients with CD was 31.44 ± 15.81 years (range: 15 to 79 years), which was significantly lower than that for patients with UC: 43.26 ± 18.63 years (range: 15 to 85 years), with a difference of 11.82 years (confidence interval [CI]: 3.05-20.59 years). No immigrants were diagnosed. The incidence related to the total population aged between 15 and 64 years old was 5.74 per 100,000 inhabitants per year (95% CI: 3.43-8.04) in CD and 9.48 per 100,000 inhabitants per year (CI: 5.63-13.32) in UC. The incidence related to the local population aged between 15 and 64 years old was 5.90 per 100,000 inhabitants per year (95% CI: 3.52-8.28) in CD and 9.75 (CI: 5.80-13.70) in UC. CONCLUSIONS: The incidence of UC in our area is one of the highest in Spain. Although this incidence is lower than that from 1994 to 1998, this decrease is not significant. The number of CD cases has not increased. Both diseases affect men and women equally. CD is diagnosed in earlier ages than UC. Exclusion of immigrants from the study increases these rates but not significantly.

Knock-down of δ-aminolevulinic acid dehydratase via virus-induced gene silencing alters the microRNA biogenesis and causes stress-related reactions in citrus plants.

The δ-aminolevulinic acid (δ-ALA) is an intermediate in the biosynthetic pathway of tetrapyrroles. Tetrapyrroles play vital roles in many biological processes such as photosynthesis, respiration, and light-sensing. ALA-dehydratase (ALAD) combines two molecules of δ-ALA to form porphobilinogen. In citrus, the silencing of ALAD caused discrete yellow spots and necrosis in leaves and stems. Additionally, it caused rapid death in developing new shoots. Herein, we hypothesize that the accumulation of δ-ALA results in severe stress and reduced meristem development. For that reason, we investigated the dynamic changes in the expression profiles of 23 microRNA (miRNA) identified through small RNA sequencing, from CTV-tALAD plants in comparison with healthy C. macrophylla and C. macrophylla infiltrated with CTV-wt. Furthermore, we reported the effect of ALAD silencing on the total phenolics, H2O2, and reactive oxygen species (ROS) levels, to examine the possibilities of miRNAs involving the regulation of these pathways. Our results showed that the total phenolics content, H2O2, and O2- levels were increased in CTV-tALAD plants. Moreover, 63 conserved miRNA members belonging to 23 different miRNA families were differentially expressed in CTV-tALAD plants compared to controls. The identified miRNAs are implicated in auxin biosynthesis and signaling, axillary shoot meristem formation and leaf morphology, starch metabolism, and oxidative stress. Collectively, our findings suggested that ALAD silencing initiates stress on citrus plants. As a result, CTV-tALAD plants exhibit reduced metabolic rate, growth, and development in order to cope with the stress that resulted from the accumulation of δ-ALA. This cascade of events led to leaf, stem, and meristem necrosis and failure of new shoot development.

Effect of Adjuvants on Oxytetracycline Uptake upon Foliar Application in Citrus.

Recently in Florida, foliar treatments using products with the antibiotics oxytetracyclineand streptomycin have been approved for the treatment of citrus Huanglongbing (HLB), which iscaused by the putative bacterial pathogen 'Candidatus Liberibacter asiaticus'. Herein, we assessedthe levels of oxytetracycline and 'Ca. L. asiaticus' titers in citrus trees upon foliar applications withand without a variety of commercial penetrant adjuvants and upon trunk injection. The level ofoxytetracycline in citrus leaves was measured using an oxytetracycline ELISA kit and 'Ca. L.asiaticus' titer was measured using quantitative PCR. Low levels of oxytetracycline were taken upby citrus leaves after foliar sprays of oxytetracycline in water. Addition of various adjuvants to theoxytetracycline solution showed minimal effects on its uptake by citrus leaves. The level ofoxytetracycline in leaves from trunk-injected trees was higher than those treated with all foliarapplications. The titer of 'Ca. L. asiaticus' in the midrib of leaves from trees receiving oxytetracyclineby foliar application was not affected after four days and thirty days of application, whereas thetiter was significantly reduced in oxytetracycline-injected trees thirty days after treatment.Investigation of citrus leaves using microscopy showed that they are covered by a thick lipidizedcuticle. Perforation of citrus leaf cuticle with a laser significantly increased the uptake ofoxytetracycline, decreasing the titer of 'Ca. L. asiaticus' in citrus leaves upon foliar application.Taken together, our findings indicate that trunk injection is more efficient than foliar spray evenafter the use of adjuvants. Our conclusion could help in setting useful recommendations for theapplication of oxytetracycline in citrus to improve tree health, minimize the amount of appliedantibiotic, reduce environmental exposure, and limit off-target effects.

Aortic valve stenosis provides complementary information to bleeding risk scores in non-valvular atrial fibrillation patients initiating anticoagulation.

BACKGROUND: The identification of modifiable bleeding risk factors may be of relevance. The aim is to evaluate if aortic stenosis (AS) provides additional information to bleeding risk scores for predicting major bleeding (MB) in non-valvular atrial fibrillation (AF). METHODS: We designed a retrospective multi-center study including 2880 consecutive non-valvular AF patients initiating oral anticoagulation between January 2013 and December 2016. AS was defined as moderate or severe according to European echocardiography guidelines criteria. HASBLED, ATRIA and ORBIT scores were used to evaluate the bleeding risk. MB was defined according to the International Society on Thrombosis and Haemostasia criteria and registered at 18 months of follow-up. RESULTS: 168 (5.8%) patients had AS. Patients with AS had higher risk for MB compared to those without AS (HR = 2.13, 95% CI: 1.40-3.23, P < 0.001). Patients without AS and low-intermediate bleeding risk (0 points) showed the lowest MB rate, whereas the MB rate observed among patients with AS and high bleeding risk (2 points) was the highest one. Discrimination and reclassification analyses showed that AS provided additional information to bleeding risk scores for predicting MB at 18 months of follow-up. CONCLUSIONS: In this population, AS was associated with an increased risk for MB at midterm follow-up. The three scoring systems showed a moderate discriminatory ability for MB. Moreover, the addition of AS was associated with a significant improvement in their predictive accuracy. We suggest that the presence of this valvulopathy should be taken into account for bleeding risk assessment.

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

INTRODUCTION: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. METHODS: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis. RESULTS: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. CONCLUSION: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.