Investigation on Dabigatran Etexilate and Worsening of Renal Function in Patients with Atrial fibrillation : the IDEA Study

BACKGROUND AND OBJECTIVES: Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function. METHOD: One hundred and seven patients treated long term with dabigatran etexilate for non-valvular atrial fibrillation (NVAF) were followed up for 90 days. DPC, serum creatinine (SCr) and serum cystatin C were prospectively measured. Ninety five patients had complete follow-up data and were evaluable for primary endpoint. RESULTS: Eleven patients had supratherapeutic DPC, defined as DPC higher than 200 ng/ml at study enrolment, but at the end of follow-up no patient showed a persistent increase in SCr. No patients experienced acute kidney injury. CONCLUSIONS: Our study shows that no persistent renal detrimental effect is associated with dabigatran treatment. An increase in SCr during dabigatran treatment is reversible and it seems to be unrelated to dabigatran itself

What hinders the uptake of computerized decision support systems in hospitals? A qualitative study and framework for implementation

Background: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. Methods: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff and members of the boards of directors (n=30). We used a constant comparative approach to develop a framework for guiding implementation. Findings: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as ‘positions’. The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians’ perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related with the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians’ reasoning and fostering organizational learning. Discussion: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians’ attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships and an organizational ethos of transparency and accountability need to considered when exploring the readiness of a hospital to adopt CDSSs.This work is supported by the Italian Ministry of Health (GR-2009-1606736), Regione Lombardia (D.R.G. IX/4340 26/10/2012), and the Wellcome Trust (WT097899)

Non-vitamin k antagonist oral anticoagulants in a European primary care physician survey

Background:Familiarity and competency in the options for stroke prevention in atrial fibrillation (AF) and the role of non-vitamin K antagonist oral anticoagulants (NOACs) may vary among primary care physicians (PCPs) from different European countries. Aims:To investigate PCP views on prescribing and managing NOACs across Europe and identify perceived unmet needs. Design & setting:Web-based survey including PCPs with particular interest in cardiovascular medicine. Method:A questionnaire was drawn up, containing 10 questions on initiation and ongoing management of NOACs; use of AF stroke guidelines on NOACs and anticoagulant switching; and perceived information needs. Results:The overall response rate was 42%. The majority of PCPs declared they are responsible for and confident in both initiating and managing NOAC therapy. In some countries, PCPs are not able to initiate NOAC therapy due to administrative barriers (namely, Italy and Slovakia). No single set of guidelines is referred to across all countries and over a fifth of responders indicate they do not follow specific guidelines. The main learning needs reported were more related to initiation than to ongoing management of anticoagulant therapy. Conclusion:According to this self-assessment survey, the experience of most PCPs in management of different aspects of AF appears good and only some felt the need for further training. However, in the light of the importance of this topic as public health issue, intensified efforts aiming at better equipping PCPs to meet their key roles in an integrated service across Europe are overdue

The definition of valvular and non-valvular atrial fibrillation : results of a physicians' survey

AIMS: To assess different aspects of the definition of valvular/non-valvular atrial fibrillation (AF) used in clinical practice by physicians who usually treat this condition.METHODS AND RESULTS: We prospectively conducted a web-based survey including cardiologists and internists who attended continuing medical education courses on cardiovascular medicine. A questionnaire was drawn up, containing 17 questions clustered into five main topics: (A) known rheumatic aetiology; (B) site/type of valve involvement; (C) prosthetic heart valve; (D) haemodynamic relevance; (E) miscellaneous. The overall response rate was 22.4% (21.1% for cardiologists and 24% for internists). Coexistence of both medical history of rheumatic disease and clinical signs of valvular involvement were considered as essential prerequisites for the diagnosis of rheumatic AF by half of the respondents, and one-third assumed that lone aortic valve disease was sufficient for AF to be defined as valvular. A similar proportion of respondents considered that in the presence of mitral regurgitation, AF had to be defined as valvular. The majority of responding physicians considered the degree of valvular defect of lesser importance for the definition of valvular or non-valvular origin of AF.CONCLUSION: We found important heterogeneity and uncertainties in the answers given by physicians who usually treat patients with AF, as evidence of the lack of precise and unique definitions of the origin of AF (valvular/non-valvular). It is urgent to issue clear widely accepted definitions of the origin of AF, which should improve clinical practice and research

Comorbidities and prognostic performance of D-Dimer in acute pulmonary embolism elderly patients

Background Risk stratification remains a critical point in patients with acute pulmonary embolism (PE). A role of D-dimer in risk assessment has been suggested in these patients, but its prognostic accuracy may be hampered by comorbidities, which are frequent in the elderly. The present study was aimed to investigated the impact of comorbidity assessment on the prognostic ability of Ddimer to predict 90-day mortality in hemodynamically stable elderly patients with acute PE. 2 Methods All consecutive hemodynamically stable patients aged >65 years old evaluated in the Emergency Department of Vimercate Hospital for clinically suspected PE since 2010 through 2014, were included in this retrospective cohort study. Pulmonary embolism was ruled out or confirmed performing a pulmonary computerized tomography angiography. Ddimer was measured and simplified Pulmonary Embolism Severity Index (sPESI) score and Charlson Comorbidity Index (CCI) score values were recorded. 3 Results Study population was represented by 162 patients. The overall mortality at 90 days was 19.8%. Baseline clinical characteristics of the study population are shown in Table 1. Table 2 shows the effect of different variables on mortality at 90 days. The difference between survival curves for low (CCI<1) and high (CCI>1) comorbidity burden patients was statistically significant (HR=4.484, p-value<0.001), Figure 1. For mortality at 90 days, HR of D-dimer was 7.74 (p-value=0.049) for patients with low and 2.68 (p-value=0.042) for patients with high comorbidity burden. When both D-dimer and sPESI were included into the model, the AUC increased in patients with low comorbidity burden, with a \ubdNRI = 0.424 (p-value=0.025), whereas the increment in AUC in patients with high comorbidity burden was smaller and the corresponding \ubdNRI was not statistically significant (p-value=0.165), Figure 2. 4 Conclusions Higher values of D-dimer, sPESI score and CCI score were associated with an increased HR for death at 90 days. D-dimer increased significantly the ability of sPESI for predicting 90-day mortality in patients with low comorbidity burden, but not in patients with high comorbidity burden. These results suggest that, in hemodynamically stable elderly patients with acute PE, comorbidities condition significantly the prognostic performance of D-dimer, which have a modest prognostic performance in patients with a high comorbidity burden, but appears to be a good predictor of death in subjects with low comorbidity burden

Comorbidity assessment as predictor of short and long-term mortality in elderly patients with hemodynamically stable acute pulmonary embolism

Elderly patients presenting with acute pulmonary embolism (PE) frequently have significant underlying comorbidities which may condition the prognosis. The current study aimed to determine the ability of Charlson comorbidity index (CCI) score to predict short and long-term mortality in elderly patients with hemodynamically stable acute PE. All hemodynamically stable patients aged >65 years with acute PE, evaluated in the Emergency Department since 2010 through 2014, were included in this retrospective cohort study. CCI, simplified pulmonary embolism severity index (sPESI) scores and vital status were recorded. Were included 162 patients with confirmed PE, out of 657 suspected cases (24.7%). Median age: 79.2 years, 74.1% presented an sPESI\u2009>\u20091 and 61.1% a CCI\u2009>\u20091. The overall 30, 90-day and 2-year mortality was 11.7% (95%CI 6.6-16.6), 19.8% (95%CI 13.4-25.7) and 31.8% (95%CI 24.1-38.8). For 30-day mortality sPESI showed an AUC 0.642 (95%CI 0.511-0.772) and adding CCI as covariate did not increase its prognostic performance. For 90-day mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.282 (95%CI 1.151-1.429, p-value\u2009<\u20090.001), and sPESI a HR\u2009=\u2009NS(p-value\u2009=\u20090.267). For 2-year mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.295 (95%CI 1.180-1.421, p-value\u2009<\u20090.001) and sPESI a HR\u2009=\u2009NS(p-value\u2009=\u20090.353). In elderly patients with hemodynamically stable PE, the CCI score was found to be an independent predictor of mortality. CCI shows a significantly better ability to predict 90-day and 2-year mortality than sPESI. The assessment of comorbidity burden by using the CCI score may be proposed as an useful tool to predict mortality in these patients

A prospective multicentre study on the treatment of cardiovascular risk factors and claudication symptoms in patients with peripheral artery disease (the IDOMENEO study)

BACKGROUND: The objective of this prospective multicenter cohort study was to characterise the use of pharmacological and non-pharmacological treatment for cardiovascular disease (CVD) risk factors and intermittent claudication (IC) symptoms in clinical practice patients with peripheral artery disease (PAD), and to determine the care gap with international guidelines and evidence-based therapy.PATIENTS AND METHODS: From 2011 through 2013, participating centres enrolled consecutive patients with PAD of atherosclerotic, origin demonstrated by ultrasound, ankle brachial index (ABI) < 0.9 and symptoms of IC. A seven item grid was built for the assessment of care gap (percentage of patients eligible for a treatment who did not receive it). cerebrovascular disease or at least two CVD risk factors. Care gap was lower than 25 % for any method to stop smoking, lipid lowering agents, antiplatelet and/or anticoagulation therapy and any kind of exercise program; between 25% and 50% for ACE inhibitors/ angiotensin II antagonist therapy; between 50% and 75% for beta-blocker therapy; and higher than 75% for supervised exercise program and use of cilostazol. Patients with and without CADI cerebrovascular disease were differently treated with clopidogrel (27.3% and 4.8 %, p < 0.001), any antiplatelet/anticoagulant therapy (98.7% and 83.3 %, p <0.001) and beta-blockers (46.8% and 16.0%, p<0.001).RESULTS: All patients (232) presented at least one CVC risk factor, 90.2% at least two, and 91.5% had either established CAD orCONCLUSIONS: Many gaps with evidence-based recommendations are still present in the pattern of the use of pharmacological and non-pharmacological treatment for CVD risk factors and IC symptoms in clinical practice PAD patients

Biosimilars of low-molecular-weight heparin products: Fostering competition or reducing 'biodiversity'?

The term "biosimilars" is used to qualify products developed to be similar to an original biological drug. Biosimilars are much more complicated to develop than a generic version of small molecule drugs and this is especially true for LMWHs. Evidence on the antithrombotic management of ACS showed that the introduction onto the market of biosimilars approved on the basis of simple biological criteria, without robust data from comparative clinical trials, may be hazardous. Moreover, the mixtures of LMWHs polysaccharide chains, some immunoallergic properties, and potential contamination during the extraction process raise safety concerns. As it was the case for the biosimilar erythropoietin, there is the risk that only copies of the most commercially successful LMWH will be marketed, thus jeopardizing the "biodiversity" now ensured by the presence of several LMWHs, each with unique features that support the use of an individual LMWH as first choice therapy in certain categories of patients. This article is protected by copyright. All rights reserved