Anticoagulation Therapy in Patients with Coronavirus Disease 2019: Results from a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 [HOPE-COVID19])

OBJECTIVES: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival. DESIGN: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019). SETTING: Hospitalized patients with coronavirus disease 2019. PATIENTS: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients. INTERVENTIONS: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient. MEASUREMENTS AND MAIN RESULTS: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation. CONCLUSIONS: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52\u201379), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer\u2013Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I\u2013IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81\u20130.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87\u20131.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399

Association analysis of grapevine bunch traits using a comprehensive approach

Key message: A set of SNP markers associated to bunch compactness and related traits were identified in grapevine. Abstract: Bunch compactness plays an important role in the sanitary status and perceived quality of table and wine grapes, being influenced by cultural practices and by environmental and genetic factors, which are mostly unknown. In this work, we took advantage of genetic, genomic and bioinformatic advances to analyze part of its molecular basis through a combination of transcriptomic and association analyses. Results from different transcriptomic comparisons between loose and compact grapevine clones were analyzed to select a set of candidate genes likely involved in the observed variation for bunch compactness. Up to 183 genes were sequenced in a grapevine collection, and 7032 single nucleotide polymorphisms (SNPs) were detected in more than 100 varieties with a frequency of the minor allele over 5 %. They were used to test their association in three consecutive seasons with bunch compactness and two of its most influencing factors: total berry number and length of the first ramification of the rachis. Only one SNP was associated with berry number in two seasons, suggesting the high sensitiveness of this trait to seasonal environmental changes. On the other hand, we found a set of SNPs associated with both the first ramification length and bunch compactness in various seasons, in several genes which had not previously related to bunch compactness or bunch compactness-related traits. They are proposed as interesting candidates for further functional analyses aimed to verify the results obtained in this work, as a previous step to their inclusion in marker-assisted selection strategies.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) through projects AGL2010-15694 and AGL2014-59171-R and grants BES-2011-047041 (JT) and RYC-2011-07791 (JG).Peer Reviewe

Dual antiplatelet therapy duration after coronary stenting in clinical practice: results of an EAPCI survey

Aims: Our aim was to report on a survey initiated by the EuropeanAssociation of Percutaneous Cardiovascular Interventions (EAPCI) concerning opinion on the evidence relating to dual antiplatelet therapy (DAPT) duration after coronary stenting.Methods and results: Results from three randomised clinical trials were scheduled to be presented at the American Heart Association Scientific Sessions 2014 (ARIA 2014). A web-based survey was distributed to all individuals registered in the EuroIntervention mailing list (n=15,200) both before and after ARIA 2014. A total of 1,134 physicians responded to the first (i.e., before AHA 2014) and 542 to the second (i.e., after ARIA 2014) survey. The majority of respondents interpreted trial results consistent with a substantial equipoise regarding the benefits and risks of an extended versus a standard DAPT strategy. Two respondents out of ten believed extended DAFT should be implemented in selected patients. After ARIA 2014, 46.1% of participants expressed uncertainty about the available evidence on DAFT duration, and 40.0% the need for clinical guidance.Conclusions: This EAPCI survey highlights considerable uncertainty within the medical community with regard to the optimal duration of DAFT after coronary stenting in the light of recent reported trial results. Updated recommendations for practising physicians to guide treatment decisions in routine clinical practice should be provided by international societies

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events