Search

The review outlines modern concepts of the relevance of fixed-dose combination therapy comprising angiotensin-converting enzyme inhibitor and dihydropyridine calcium channel antagonist as an antihypertensive component with the HMG-CoA reductase inhibitor when treating hypertensive patients. We have identified the realms of its possible clinical use taking into consideration the comorbidity peculiarities. In addition, we provide main features of the current drugs’ clinical pharmacodynamics and outline their role in real clinical practice. Nevertheless the emphasis was placed on the modern single-pill combination of amlodipin, atorvastatin and perindopril. We concisely report the results data collected from the large, randomized, double-blind major clinical trials regarding the effectiveness of single pill combination of amlodipine, atorvastatin and perindopril , primary focusing on their cardioprotective features and overall safety profile.

Background: The development of prosthetic valves for the treatment of cardiovascular conditions has transformed medicine and given patients with valvular heart disease effective treatment options. Purpose of the study: This article will examine the existing problems with prosthetic valves, including thrombosis, calcification, and infection brought on by the device. Problem statement: Despite their success, prosthetic valves continue to pose a number of problems, and in order to further increase their efficacy and safety, future trends need to be recognized. Method materials: The current study would be completed with the help of the Secondary data collection method to collect data to complete the study with the extracted data. Then the gathered at is analysed with the qualitative data analysis method. Major findings: This article will examine the existing problems with prosthetic valves, including thrombosis, calcification, and infection brought on by the device, as well as upcoming trends, including the creation of new materials, new designs, and enhanced imaging techniques. Novelty: It is intended that this review will assist readers to gain a better grasp of the present and emerging developments in prosthetic valve technology and point out relevant directions for further study. [ABSTRACT FROM AUTHOR]

Abstract Background Polypharmacy is inevitable and appropriate for many conditions, but in some cases, it can be problematic resulting in an increased risk of harm and reduced quality of life. There has been an increasing interest to reduce cardioprotective medications in older adults to potentially reduce the risk of harm due to treatment; however, there is no evidence on safety and efficacy to support this practice currently. This paper describes a protocol for a systematic review on the safety and efficacy of reducing cardioprotective medication in older populations. Methods MEDLINE (PubMed), Embase (Ovid), and CENTRAL (Cochrane Central Register of Controlled Trials) will be searched from their inception onwards for relevant studies. Randomised controlled trials and non-randomised studies on interventions (prospective, retrospective cohort, case-control) conducted in older adults (75 years or older) examining reduction of cardioprotective medications will be included. The primary outcome of this study will be all-cause hospitalisation. Secondary outcome variables of interest are all-cause hospitalisation, mortality, quality of life, serious adverse events, major adverse cardiovascular events, falls, fractures, cognitive functioning, bleeding events, renal functioning, medication burden, drug reinstatement, time-in-hospital, and frailty status. Two reviewers will independently screen all citations, full-text articles, and extract data. Confidence in cumulative evidence will be assessed using the GRADE approach; the risk of bias will be assessed by the RoB-II tool for randomised controlled studies and ROBINS-I for non-randomised studies. Where sufficient data are available, we will conduct a random effects meta-analysis by combining the outcomes of the included studies. Sub-group analysis and meta-regression are planned to assess the potential harms and risks of different drug classes and the impacts in different patient populations (e.g. sex, cognitive status, renal status, and age). Discussion The study will be a comprehensive review on all published articles identified using our search strategy on the safety and efficacy of cardioprotective medication reduction in the older population. The findings will be crucial to inform clinicians on potential health outcomes of reducing cardiovascular medication in the elderly. Systematic review registration PROSPERO CRD42020208223

Background: The widely variable clinical manifestations of SARS-CoV2 disease (COVID-19) range from asymptomatic infections to multiple organ failure and death. Among the organs affected is the heart. This does not only affect people who already have previous cardiovascular problems, but also healthy people. This is a reason not to overlook any symptoms or to perform targeted examinations, even if apparently unrelated to the heart, for quick recognition and timely therapy. Aim of the study: This review recapitulates the current state of knowledge on the potential mechanisms and manifestation of myocarditis in patients with COVID-19 infection. Methods: A web-based search of published data was performed for all relevant studies on patients diagnosed with a COVID-19-induced acute myocarditis, and a total of 50 reports were included. The analysis of the studies evaluated highlights a male predominance, with the average age of patients being 55 years. The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. Finally, we wanted to use a general evaluation without distinguishing between various countries, taking into consideration only the peer or reviewer, regardless of the declared value of the journals that have been published. Results and critical findings: The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. In most patients, elevated levels of cardiac and inflammatory biomarkers were measured. Left ventricular dysfunction and hypokinesis were commonly exhibited symptoms. Cardiac Magnetic Resonance Imaging (CMRI) confirmed the diagnosis of myocarditis with features of cardiac edema and cardiac injury. Nine patients underwent histopathological examination. Treatment with corticosteroids and immunoglobulins was the most applied strategy following the administration of antivirals. Discussion: Despite the exponentially growing knowledge on the management of COVID-19 infection, current available data on SARS-CoV2-correlated myocarditis are still limited, and several difficulties may be encountered in the differential diagnosis of acute myocarditis in the context of COVID-19 disease. Conclusions: While diagnostic criteria and evaluation strategies for myocarditis are well described, no guidelines for the diagnosis and treatment of myocarditis in COVID-19 patients have yet been established. Therefore, further research is needed to advance the understanding of this disease process and define the most appropriate strategic approach in these patients.

Background and PurposeMultiple guidelines suggest the ω-3 polyunsaturated fatty acids (ω-3 PUFAs) help to prevent major vascular events of coronary heart disease (CHD), but the data on large trials of ω-3 fatty acids are controversial. We reviewed the available evidence to determine the effect of ω-3 PUFAs on coronary atherosclerosis.Materials and MethodsLiterature were from online databases. Randomized controlled trials (RCTs) or observational studies were acceptable. Quantitative data synthesis was conducted using R version 4.1.2. Each outcome was calculated using standardized mean difference (SMD) in a random-effect model. Sensitivity analysis was conducted for each outcome. A total of 21 RCTs and 1 observational study with 2,277 participants were included.ResultsMeta-analysis indicated a benefit of ω-3 PUFAs on coronary atherosclerosis, namely, (1) ω-3 PUFAs can reduce the atherosclerotic plaque volume (SMD −0.18; 95% CI −0.31 to −0.05); (2) ω-3 PUFAs can help reduce the loss of the diameter of the narrowest segments of coronary arteries in patients with CHD (SMD 0.29; 95% CI, 0.05–0.53); (3) ω-3 PUFAs do not have significant effect on volume of lipid plaque in coronary arteries (SMD −1.18; 95% CI −2.95 to 0.58), volume of fiber plaque (SMD 0.26; 95% CI −0.81 to 1.33), and calcified plaque (SMD 0.17; 95% CI −0.55 to 0.89); and (4) ω-3 PUFAs had no significant effect on endothelial inflammatory factors in peripheral blood.ConclusionsWe confirmed that ω-3 PUFAs benefit patients with CHD by reducing the progression of coronary atherosclerosis. We indicated that the benefits were not caused by reducing endothelial inflammations of coronary arteries.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021285139, identifier: CRD42021285139.

Anticoagulant therapy in elderly patients with atrial fibrillation and concomitant diseases is often the challenge for clinicians. The high risk of stroke is inherent in atrial fibrillation, and it increases when combined with coronary heart disease and chronic kidney disease. On the other hand, the comorbidity increases the risk of bleeding. Older age is also the risk factor of thrombotic and hemorrhagic complications. As a consequence, the choice of specific anticoagulant should be based on a solid evidences, obtained both from randomized clinical trials and from daily clinical practice. In the ROCKET AF trail the direct oral anticoagulant rivaroxaban showed a tendency to reduce the risk of thromboembolism by 20% compared with warfarin in the patients aged 75 years and older. The safety of rivaroxaban has been evaluated in the XANTUS POOLED program. According to the follow-up results for 12 months, more than 96% of patients didn't have any adverse event, and the number of patients with major bleeding was 1.5%. Several meta-analyzes reported a reduction of cardiovascular complications in patients treated by rivaroxaban. In the ROCKET AF trail, a “renal” dose of rivaroxaban (15 mg OD) was studied in patients with chronic kidney disease. The efficacy and safety of rivaroxaban were validated in this patients, and a simple algorithm for selecting the dose of this drug in patients with chronic kidney disease was provided.

Owing to myocardial abnormalities, cardiac ailments are considered to be the major cause of morbidity and mortality worldwide. According to a recent study, membranous vesicles that are produced naturally, termed as “exosomes”, have emerged as the potential candidate in the field of cardiac regenerative medicine. A wide spectrum of stem cells has also been investigated in the treatment of cardiovascular diseases (CVD). Exosomes obtained from the stem cells are found to be cardioprotective and offer great hope in the treatment of CVD. The basic nature of exosomes is to deal with the intracellular delivery of both proteins and nucleic acids. This activity of exosomes helps us to rely on them as the attractive pharmaceutical delivery agents. Most importantly, exosomes derived from microRNAs (miRNAs) hold great promise in assessing the risk of CVD, as they serve as notable biomarkers of the disease. Exosomes are small, less immunogenic, and lack toxicity. These nanovesicles harbor immense potential as a therapeutic entity and would provide fruitful benefits if consequential research were focused on their upbringing and development as a useful diagnostic and therapeutic tool in the field of medicine.

Background: Polypharmacy is inevitable and appropriate for many conditions, but in some cases, it can be problematic resulting in an increased risk of harm and reduced quality of life. There has been an increasing interest to reduce cardioprotective medications in older adults to potentially reduce the risk of harm due to treatment; however, there is no evidence on safety and efficacy to support this practice currently. This paper describes a protocol for a systematic review on the safety and efficacy of reducing cardioprotective medication in older populations. Methods: MEDLINE (PubMed), Embase (Ovid), and CENTRAL (Cochrane Central Register of Controlled Trials) will be searched from their inception onwards for relevant studies. Randomised controlled trials and non-randomised studies on interventions (prospective, retrospective cohort, case-control) conducted in older adults (75 years or older) examining reduction of cardioprotective medications will be included. The primary outcome of this study will be all-cause hospitalisation. Secondary outcome variables of interest are all-cause hospitalisation, mortality, quality of life, serious adverse events, major adverse cardiovascular events, falls, fractures, cognitive functioning, bleeding events, renal functioning, medication burden, drug reinstatement, time-in-hospital, and frailty status. Two reviewers will independently screen all citations, full-text articles, and extract data. Confidence in cumulative evidence will be assessed using the GRADE approach; the risk of bias will be assessed by the RoB-II tool for randomised controlled studies and ROBINS-I for non-randomised studies. Where sufficient data are available, we will conduct a random effects meta-analysis by combining the outcomes of the included studies. Sub-group analysis and meta-regression are planned to assess the potential harms and risks of different drug classes and the impacts in different patient populations (e.g. sex, cognitive status, renal status, and age). Discussion: The study will be a comprehensive review on all published articles identified using our search strategy on the safety and efficacy of cardioprotective medication reduction in the older population. The findings will be crucial to inform clinicians on potential health outcomes of reducing cardiovascular medication in the elderly. Systematic review registration: PROSPERO CRD42020208223 [ABSTRACT FROM AUTHOR]

Lopinavir-ritonavir combination is being used for the treatment of SARS-CoV-2 infection. A low dose of ritonavir is added to other protease inhibitors to take advantage of potent inhibition of cytochrome (CYP) P450 3A4, thereby significantly increasing the plasma concentration of coadministered lopinavir. Ritonavir also inhibits CYP2D6 and induces CYP2B6, CYP2C19, CYP2C9, and CYP1A2. This potent, time-dependent interference of major hepatic drug-metabolizing enzymes by ritonavir leads to several clinically important drug-drug interactions. A number of patients presenting with acute coronary syndrome and acute heart failure may have SARS-CoV-2 infection simultaneously. Lopinavir-ritonavir is added to their prescription of multiple cardiac medications leading to potential drug-drug interactions. Many cardiology, pulmonology, and intensivist physicians have never been exposed to clinical scenarios requiring co-prescription of cardiac and antiviral therapies. Therefore, it is essential to enumerate these drug-drug interactions, to avoid any serious drug toxicity, to consider alternate and safer drugs, and to ensure better patient care. [ABSTRACT FROM AUTHOR]

The cardiovascular system is mainly responsible for the transport of substances necessary to cellular metabolism. However, for the good performance of this function, there is need for adequate control of blood pressure levels of tissue perfusion and systemic arterial. Acute myocardial infarction is one of the complications of the cardiovascular system, that most affects the population around the world. This condition can be defined as a disease generated by an imbalance of oxygen concentrations used in cardiovascular metabolism, this change usually occurs because coronary occlusion, which prevents myocardial blood flow. The diagnosis is based on the set of clinical and laboratory investigations, which are in the release of cardiac enzyme biomarkers, cardiovascular and hemodynamic changes and cardiac accommodations. The treatment consists in the use of concomitant cardiovascular drugs, such as: antihypertensive, antiplatelet and hypolipidemic. Despite improvements in clinical and pharmacological management, acute myocardial infarction remains the leading cause of death worldwide. This finding encourages the scientific research of new drugs for the treatment of myocardial infarction or supporting therapies aimed at reducing the levels of deaths and comorbities generated by cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Nattokinase is a fibrinolytic enzyme identified and isolated in 1987 from a specific Japanese food called natto (a kind of vegetable cheese). Since its discovery and until now, nattokinase has been studied experimentally and clinically almost exclusively in Japan, China, Korea and other countries in the respective geographical area, resulting in a complex picture of potentially useful properties in clinical practice. Nattokinase was approved for use in Europe in 2016 by EFSA (European Food Safety Authority) as a food supplement.

Background: The widely variable clinical manifestations of SARS-CoV2 disease (COVID-19) range from asymptomatic infections to multiple organ failure and death. Among the organs affected is the heart. This does not only affect people who already have previous cardiovascular problems, but also healthy people. This is a reason not to overlook any symptoms or to perform targeted examinations, even if apparently unrelated to the heart, for quick recognition and timely therapy. Aim of the study: This review recapitulates the current state of knowledge on the potential mechanisms and manifestation of myocarditis in patients with COVID-19 infection. Methods: A web-based search of published data was performed for all relevant studies on patients diagnosed with a COVID-19- induced acute myocarditis, and a total of 50 reports were included. The analysis of the studies evaluated highlights a male predominance, with the average age of patients being 55 years. The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. Finally, we wanted to use a general evaluation without distinguishing between various countries, taking into consideration only the peer or reviewer, regardless of the declared value of the journals that have been published. Results and critical findings: The most common presenting symptoms included fever, shortness of breath, cough, and chest pain. Among ECG changes, non-specific ST-segment and T-wave amplitude alterations and ventricular tachycardia episodes were reported. In most patients, elevated levels of cardiac and inflammatory biomarkers were measured. Left ventricular dysfunction and hypokinesis were commonly exhibited symptoms. Cardiac Magnetic Resonance Imaging (CMRI) confirmed the diagnosis of myocarditis with features of cardiac edema and cardiac injury. Nine patients underwent histopathological examination. Treatment with corticosteroids and immunoglobulins was the most applied strategy following the administration of antivirals. Discussion: Despite the exponentially growing knowledge on the management of COVID-19 infection, current available data on SARS-CoV2-correlated myocarditis are still limited, and several difficulties may be encountered in the differential diagnosis of acute myocarditis in the context of COVID-19 disease. Conclusions: While diagnostic criteria and evaluation strategies for myocarditis are well described, no guidelines for the diagnosis and treatment of myocarditis in COVID-19 patients have yet been established. Therefore, further research is needed to advance the understanding of this disease process and define the most appropriate strategic approach in these patients. [ABSTRACT FROM AUTHOR]

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Adherence to chronic medications remains poor in practice. There is limited evidence on how hospitalization affects post‐discharge adherence to oral anticoagulants (OACs) in individuals with atrial fibrillation. The aim of this study was to examine the impact of hospitalization and medication switching on post‐discharge adherence to OACs in the population with atrial fibrillation. Methods: A quasi‐experimental pre–post observational study was conducted using United States commercial insurance health care claims from the 2009 to 2016 Optum database. Adults with atrial fibrillation taking OACs who had a random hospitalization occurring after the first observed OAC prescription fill and no other admission in the preceding and following 6 months were identified. OAC adherence was estimated by the proportion of days covered within 6 and 12 months before and after hospitalization. Difference‐in‐difference analysis was employed to compare the pre‐hospitalization and post‐hospitalization proportion of days covered, stratified by reasons for hospitalization (i.e., bleeding vs non–bleeding‐related reasons) and adjusting for imbalanced baseline characteristics between groups. Change in adherence when the OAC was switched at discharge was also examined. Results: The 22,429 individuals who met study criteria were predominantly male (52.4%), white (77.2%), and older age (median 74 years). A clinically significant hemorrhage was the reason for 1029 (4.5%) of qualifying hospitalizations. After covariate adjustment, there was a reduction in the proportion of days covered after discharge, regardless of admission diagnosis (p<0.0001). The 6‐month difference‐in‐difference analyses revealed that adherence was incrementally reduced by 3.2% (p=0.0003) in the bleeding group compared with the nonbleeding group, whereas switching from warfarin to a direct oral anticoagulant after hospitalization was associated with a smaller reduction by 3.4% in adherence (p=0.0342) compared with other switchers, regardless of the reason for hospitalization. The 12‐month difference‐in‐difference analyses revealed similar results. Conclusions: Hospitalization is temporally associated with a reduction in adherence to OACs, regardless of reason for hospitalization. More effective strategies are needed to improve OAC adherence, particularly during transition of care [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of morbidity and mortality in adults in western nations. In the last decades, tremendous research has been conducted in the field of secondary prevention in order to reduce recurrent cardiovascular events. This review summarizes the novel dual pathway concept of aspirin and very low-dose rivaroxaban, from mechanisms to clinical practice. The COMPASS trial demonstrated that in patients with stable atherosclerotic disease, very low-dose rivaroxaban, a direct factor Xa inhibitor, when combined with aspirin, reduced the rate of recurrent ischemic events, at the cost of increased bleeding. This effect was present in patients with ischemic heart disease, as well as in patients with atherosclerosis in other beds, such as in peripheral arterial disease. Sub-studies from the COMPASS trial examined other high-risk populations who might benefit the most from this regimen. There are currently multiple antiplatelet and anticoagulation treatment regimens for patients with stable atherosclerotic disease. The dual pathway concept is a novel approach that combines both mechanisms. Identifying patients who might benefit the most in terms of ischemic events at the least bleeding events still remains a challenge, yet prescribing this combination to high-risk patients might be the most effective. [ABSTRACT FROM AUTHOR]

Background: Studies have reported that natriuretic peptides provide prognostic information for emergency department (ED) syncope.Objective: To evaluate whether adding N-terminal pro-B-type natriuretic peptide (NT-proBNP) to the Canadian Syncope Risk Score (CSRS) improves prediction of 30-day serious adverse events (SAEs).Design: Prospective cohort study.Setting: 6 EDs in 2 Canadian provinces.Participants: 1452 adult ED patients with syncope.Intervention: Serum NT-proBNP was measured locally at 1 site and batch processed at a central laboratory from other sites. The concentrations were not available to treating physicians or for adjudication of outcomes.Measurements: An adjudicated composite outcome of 30-day SAEs, including death and cardiac (arrhythmic and nonarrhythmic) and noncardiac events.Results: Of 1452 patients enrolled, 152 (10.5% [95% CI, 9.0% to 12.1%]) had 30-day SAEs, 57 (3.9%) of which were identified after the index ED disposition. Serum NT-proBNP concentrations were significantly higher among patients with SAEs than those without them (median, 626.5 ng/L vs. 81 ng/L; P < 0.001). Adding NT-proBNP values to the CSRS did not significantly improve prognostication (c-statistic, 0.89 and 0.90; P = 0.12 for difference), regardless of SAE subgroup or whether the SAE was identified after the index ED visit. The net reclassification index shows that NT-proBNP would have correctly reclassified 3% of patients with SAEs at the expense of incorrectly reclassifying 2% of patients without SAEs.Limitations: Our study was powered to detect a 3% difference in the area under the curve. The heterogeneity of outcomes and robust baseline discrimination by the CSRS will make improvements challenging.Conclusion: Although serum NT-proBNP concentrations were generally much higher among ED patients with syncope who had a 30-day SAE, this blood test added little new information to the CSRS. Routine use of NT-proBNP for ED syncope prognostication is not recommended.Primary Funding Source: Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research, and The Ottawa Hospital Academic Medical Organization. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems. [ABSTRACT FROM AUTHOR]

Aging-related cellular and molecular processes including low-grade inflammation are major players in the pathogenesis of cardiovascular disease (CVD) and Alzheimer's disease (AD). Epidemiological studies report an independent interaction between the development of dementia and the incidence of CVD in several populations, suggesting the presence of overlapping molecular mechanisms. Accumulating experimental and clinical evidence suggests that amyloid-beta (Aβ) peptides may function as a link among aging, CVD, and AD. Aging-related vascular and cardiac deposition of Αβ induces tissue inflammation and organ dysfunction, both important components of the Alzheimer's disease amyloid hypothesis. In this review, the authors describe the determinants of Aβ metabolism, summarize the effects of Aβ on atherothrombosis and cardiac dysfunction, discuss the clinical value of Αβ1-40 in CVD prognosis and patient risk stratification, and present the therapeutic interventions that may alter Aβ metabolism in humans. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulant therapy (VKA) is nowadays the mainstay of treatment in primary and secondary stroke prevention in patients with atrial fibrillation. Given the limited risk-benefit ratio of vitamin K antagonists, pharmacological research has been directed towards the development of products that could overcome these limits, new oral anticoagulants were recently introduced: dabigatran, rivaroxaban, apixaban, and edoxaban. Aim: Scope of the present study was to examine patterns of use, effectiveness, safety and mean annual cost per patient of anticoagulant treatment for non-valvular AF in real clinical practice. Methods: A retrospective observational cohort study, by using administrative databases (drugs, hospitalizations, clinical visits, lab tests, population registry), was conducted in the Local Health Unit (LHU) of Treviso, Italy, from January 1, 2012 to December 31, 2016. Results: 5597 subjects were selected, 2171 of which satisfied all inclusion criteria. In particular 1355 patients were treated with VKA, 577 patients were treated with NOAC, and 239 patients were treated initially with VKA and subsequently switched to NOAC (switch group). NOAC treatment showed to be superior to VKA and this superiority was statistically significant on both end-points: patients in the NOAC group reported less cardiovascular events (9,9%) and less bleeding episodes (5,5%) versus VKA patients (14,6% and 11,4%; p<,0001 and p = 0,0049, respectively). The mean cost per patient per year was respectively € 1323,9 for patients treated with NOAC versus € 1003,3 for patients treated with VKA. Cost difference appears to be largely driven by drug cost (€ 767,9 for NOAC versus € 17,7 for VKA patients) and by specialist visits and laboratory tests (€ 318,4 for NOAC versus € 733,4 for VKA patients). Conclusion: In this retrospective real-world study treatment with NOAC showed to be associated with significant reductions of CV events and bleeding events compared to VKA use, albeit at a higher NHS’ direct cost per patient/year, mainly due to higher drug therapy cost. [ABSTRACT FROM AUTHOR]

Aims: The international-normalized-ratio (INR) is typically used to monitor patients on warfarin or related oral anticoagulant therapy. The aim of our study was to investigate the association of the INR with mortality in coronary artery disease (CAD) patients not on oral anticoagulant therapy. Methods and results: Between 1997 to 2000 the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study enrolled 3316 patients of German ancestry that had been referred for coronary angiography. We excluded patients on coumarin therapy (n = 222) and patients with an INR more than 5 standard deviations (SD) away from the mean (n = 30). During a median follow-up of 9.9 years, 884 patients died, 547 patients from cardiovascular causes. After adjustment for cardiovascular risk factors the INR was associated with all-cause mortality in all patients and the CAD positive group with HRs (95% CI) of 1.14(1.07–1.21) and 1.16(1.09–1.23) per 1-SD increase, respectively. Adjustment for NT-proBNP rendered the association insignificant. Conclusion: In LURIC, the INR was positively associated with mortality in patients with prevalent CAD not on oral anticoagulant therapy as well as in patients without CAD. Adjustment for NT-proBNP abolished the association suggesting clinical or subclinical heart failure strongly contributing to increased INR and higher mortality. [ABSTRACT FROM AUTHOR]

Introduction: The closed testing principle provides strong control of the type I error probabilities of tests of a set of hypotheses that are closed under intersection such that a given hypothesis H can only be tested and rejected at level α if all intersection hypotheses containing that hypothesis are also tested and rejected at level α. For the higher order hypotheses, multivariate tests (> 1df) are generally employed. However, such tests are directed to an omnibus alternative hypothesis of a difference in any direction for any component that may be less meaningful than a test directed against a restricted alternative hypothesis of interest. Methods: Herein we describe applications of this principle using an α-level test of a surrogate hypothesis such that the type I error probability is preserved if such that rejection of implies rejection of H. Applications include the analysis of multiple event times in a Wei-Lachin test against a one-directional alternative, a test of the treatment group difference in the means of K repeated measures using a 1 df test of the difference in the longitudinal LSMEANS, and analyses within subgroups when a test of treatment by subgroup interaction is significant. In such cases the successive higher order surrogate tests can be aimed at detecting parameter values that fall within a more desirable restricted subspace of the global alternative hypothesis parameter space. Conclusion: Closed testing using α-level tests of surrogate hypotheses will protect the type I error probability and detect specific alternatives of interest, as opposed to the global alternative hypothesis of any difference in any direction. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) are administered in fixed doses without monitoring. There is still little published data on the impact of the absence of monitoring on adherence to medication and stability of DOAC plasma levels over time. Objectives: To explore adherence and stability of DOAC plasma levels over time in patients with atrial fibrillation (NVAF) recently started on DOAC therapy. Patients and methods: A prospective observational cohort study with structured follow up including assessment of adherence to medication, plasma levels at baseline, 3,6 and 12 months and adverse events. Results: We included 164 patients; 89% were previous users of a vitamin K antagonist (VKA). One-year adherence was reasonably good: Morisky adherence measurement scores of 6–8 in 92%. The majority of DOAC plasma levels were within reported on-therapy ranges; dabigatran (median 104.4 ng/ml, IQR 110.2), rivaroxaban (median 185.2 ng/ml, IQR 216.1) and on average levels were not different for full and adjusted doses. There was significant variation between patients, but no significant differences over time within individuals. A substantial proportion of patients starting in the upper-or lower 20th percentiles remained there during the entire follow up. Seventeen bleedings (16 minor, 1 major) were reported, no ischemic events and bleeding or thrombotic events were not associated with DOAC plasma levels. Conclusions: Adherence was reasonably good in the majority of patients. Our data confirm the stability of DOAC plasma levels over time. Knowledge of such data may, in the individual patient, contribute to optimal drug and dose selection. [ABSTRACT FROM AUTHOR]

The article offers information on the clinical practice and evidence-based management of heart failure. Topics discussed the need for high-quality implementation science to integrate and embed research advances into clinical practice; mentions the initiation of combination therapy with beta blocker and angiotensin-converting enzyme (ACE) inhibitor; and highlights the initiatives to improve standards in heart failure treatment that focused on primary and secondary care.

Background: Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation. Methods: A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model. Results: 18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13–0.39) and DOAC (RRs ranging from 0.25–0.32; 95%CI ranging from 0.13–0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34–4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37–7.16) and standard-dose (RR 3.23; 95%CI 1.16–8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths. Conclusion: Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • QSAR models for ROCK inhibitory action of urea derivates were developed. • Monte Carlo method with SMILES notation and molecular graph descriptors was used. • Different methods were applied for the determination of the robustness of the model. • Molecular fragments with influence on inhibitory action were determined. • Presented study can be useful in the search for novel cardiovascular therapeutics. Abstract Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set. Molecular descriptors used for QSAR modeling were based on the SMILES notation and local invariants of the molecular graph. The statistical quality of the developed model, including robustness and predictability, was tested with different statistical approaches and satisfying results were obtained. The best calculated QSAR model had the following statistical parameters: r2 = 0.8825 and q2 = 0.8626 for the training set and r2 = 0.9377 and q2 = 0.9124 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for the final model assessment, and the obtained results were 0.6631 for the training and 0.9683 for the test set. Molecular fragments responsible for the increases and decreases of the studied activity were defined and they were further used for the computer-aided design of new compounds as potential Rho kinase inhibitors. The final assessment of the developed QSAR model and designed inhibitors was achieved with the application of molecular docking. An excellent correlation between the results from QSAR and molecular docking studies was obtained. [ABSTRACT FROM AUTHOR]

Background: Non-vitamin K antagonist oral anticoagulants (NOAC) are equally or potentially superior in terms of effectiveness in the prevention of ischemic stroke and carry a lower associated risk of intracranial hemorrhage compared to Vitamin K antagonists. Nevertheless, ischemic strokes also occur in patients who are being treated with NOAC. In those particular patients, knowledge about the underlying stroke etiology, clinical presentation, acute management, and complication rates is scarce. Objective: Systematic literature review to provide a comprehensive clinical overview in terms of presentation, laboratory, imaging parameters and outcomes of patients suffering from acute cerebral ischemic events (i.e. TIA and acute ischemic stroke) while on treatment with a NOAC. Only if available, comparison to VKA is presented which was not the primary focus of this analysis. Data sources: PubMed/MEDLINE, Scopus and EMBASE from January 1, 2006, to November 20, 2018. Study eligibility criteria: 52 studies providing detailed information on a total of 12247 patients were included. We excluded case reports and case series with less than five patients. Study appraisal and synthesis method: We systematically assessed study quality using a bias tool and pooled consistent data. Results: Existing data indicates milder stroke severity and smaller infarct size of acute ischemic stroke on treatment with NOAC compared to stroke occurrence on Vitamin K antagonists (VKA). Established risk factors for ischemic events also play a role in stroke while on NOACs, albeit the underlying etiology remains poorly understood. Intravenous thrombolysis and endovascular therapy seem to be safe and effective, but patient selection for recanalization therapies is challenging. Limitations: Limited quality of published data, duplicate cases, statistical issues of data pooling, possible incomplete retrieval of identified research and reporting bias might have limited our findings. Conclusions: Acute ischemic events despite treatment with NOAC therapy are insufficiently investigated. Systematic review registration number: PROSPERO: CRD42018074853. [ABSTRACT FROM AUTHOR]

Background: Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT. Methods: We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications. Results: We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42–0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40–0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11–2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54–1.01). Both DOAC (HR 0.42; 95% CI 0.29–0.61) and LMWH (HR 0.57; 95% CI 0.44–0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding. Conclusions: DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated low-intensity warfarin (INR target of 1.5–2.5) achieved reduced hemorrhage without increasing thromboembolism for Asians with non-valvular atrial fibrillation (NVAF). Whether non-vitamin K antagonist oral anticoagulant (NOAC) is superior to warfarin with good time in the therapeutic range (TTR) based on lower INR target among Asians with NVAF remains unknown. Methods: In this retrospective study collected from Taiwan Chang Gung Memorial Hospital Database, there were 5,197, 3,396, and 9,898 consecutive patients taking warfarin, NOAC, and no-treatment, respectively, from January 1, 2000 to December 31, 2015. Propensity-score weighting was used across the study groups. Patients were followed until the first occurrence of study outcome or end date of study. Results: Among those patients taking warfarin, the mean”artificial” TTR (aTTR) based on a lower INR target of 1.5–2.5 was 44.4±33.3%. Total 79.2% (n = 2,690) patients took low-dose NOACs. Patients with aTTR in the range from <30%(34.0%), 30–50%(17.6%), 50–70%(23.5%) to >70%(24.9%) showed decremental risks of efficacy and composite outcome compared with no-treatment. The risk of major bleeding didn’t increase among patients with top aTTR>70% compared to no-treatment. The NOAC group showed a comparable risk of composite outcome to the warfarin subgroup with aTTR of >70% (P = 0.485). The NOAC group had a lower risk of composite outcome than warfarin subgroup with TTR of>70% based on the INR target of 2.0–3.0 (P = 0.004). Conclusions: NOACs showed a comparable risk of efficacy, safety, and composite outcome to well-managed warfarin based on a lower INR target of 1.5–2.5 in Asians with NVAF taking oral anticoagulants. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the accuracy of Spectral Photon-Counting Computed Tomography (SPCCT) in the quantification of iodine concentrations and its potential for the differentiation between blood and iodine. Methods: Tubes with blood and a concentration series of iodine were scanned with a preclinical SPCCT system (both in vitro and in an ex vivo bovine brain tissue sample). Iodine density maps (IDM) and virtual non-contrast (VNC) images were generated using the multi-bin spectral information to perform material decomposition. Region-of-interest (ROI) analysis was performed within the tubes to quantitatively determine the absolute content of iodine (mg/ml). Results: In conventional CT images, ROI analysis showed similar Hounsfield Unit (HU) values for the tubes with blood and iodine (59.9 ± 1.8 versus 59.2 ± 1.5). Iodine density maps enabled clear differentiation between blood and iodine in vitro, as well as in the bovine brain model. Quantitative measurements of the different iodine concentrations matched well with those of actual known concentrations even for very small iodine concentrations with values below 1mg/ml (RMSE = 0.19). Conclusions: SPCCT providing iodine maps and virtual non-contrast images allows material decomposition, differentiation between blood and iodine in vitro and ex vivo in a bovine brain model and reliably quantifies the iodine concentration. [ABSTRACT FROM AUTHOR]

Background: Structured secondary cardiovascular prevention programs (SSCP) following acute coronary syndromes (ACS) may reduce major adverse cardiovascular events (MACE) through better adherence to post-ACS recommendations. Methods: Through a prospective multicenter cohort study, we compared the outcomes of two sequential post-ACS patient cohorts, the initial one receiving standard care (SC) followed by one receiving additional interventions (SSCP) aimed at improving patient education as well as healthcare provider and hospital systems. The primary endpoint was MACE at one year. Secondary endpoints included adherence to recommended therapies, attendance to cardiac rehabilitation (CR) and successful achievement of cardiovascular risk factor (CVRF) targets. Results: In total, 2498 post-ACS patients from 4 Swiss university hospitals were included: 1210 vs 1288 in the SC and SSCP groups, respectively. The SSCP group demonstrated a significant increase in attendance to CR programs (RR 1.08, 95%CI 1.02–1.14, P = 0.006), despite not achieving the primary MACE endpoint (HR 0.97, 95%CI 0.77–1.22, P = 0.79). After age-stratification, significant reductions in cardiac death, MI and stroke events (HR 0.53, 95%CI 0.30–0.93, P for interaction = 0.016) were observed for SSCP patients ≤ 65 years old. The SSCP group also scored significantly better for the LDL cholesterol target (RR 1.07, 95%CI 1.02–1.13, P = 0.012), systolic blood pressure target (RR 1.06, 95%CI 1.01–1.13, P = 0.029) and physical activity (RR 1.10, 95%CI 1.01–1.20, P = 0.021). Conclusions: The implementation of an SSCP post ACS was associated with an improvement in the control of CVRF and attendance to CR programs, and was also associated with significant reductions in cardiac death, MI and stroke at one year for patients ≤65years old. [ABSTRACT FROM AUTHOR]

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76–1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69–1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: We investigated the recent 10-year trends in the number of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in relation to prescription patterns of antithrombotic therapy. Methods: We analyzed the annual prevalence of PCI and patterns of antithrombotic therapy after PCI, including antiplatelets and oral anticoagulants (vitamin K antagonists and non-vitamin K antagonist oral anticoagulants [NOACs]), in patients with AF between 2006 and 2015 by using the Korean National Health Insurance Service database. Independent factors associated with triple therapy (oral anticoagulant plus dual antiplatelet) prescription were assessed using multivariable logistic regression analysis. Results: The number of patients with AF undergoing PCI increased gradually from 2006 (n = 2,140) to 2015 (n = 3,631) (ptrend<0.001). In 2006, only 22.7% of patients received triple therapy after PCI although 96.2% of them were indicated for anticoagulation (CHA2DS2-VASc score ≥2). The prescription rate of triple therapy increased to 38.3% in 2015 (ptrend<0.001), which was mainly attributed to a recent increment of NOAC-based triple therapy from 2013 (17.5% in 2015). Previous ischemic stroke or systemic embolism, old age, hypertension, and congestive heart failure were significantly associated with a higher triple therapy prescription rate, whereas previous myocardial infarction, PCI, and peripheral arterial disease were associated with triple therapy underuse. Conclusions: From 2006 to 2015, the number of patients with AF undergoing PCI and the prescription rate of triple therapy increased gradually with a recent increment of NOAC-based antithrombotic therapy from 2013. Previous myocardial infarction, peripheral artery disease, and PCI were associated with underuse of triple therapy. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia among adults. Despite the proven advantages in primary and secondary stroke prevention in patients with AF, oral anticoagulation (OAC) therapy is still underused in many countries. In this study, we investigated the incidence of AF-related ischemic stroke over the past decade in South Korea and trends of preventive antithrombotic therapy use before stroke in a nationwide cohort. Methods and findings: The data source for this study was a nationwide sample cohort comprising 1,025,340 individuals that was established by the nationwide health insurance system in 2002. A total of 10,215 patients with acute ischemic stroke (AIS) were selected from the cohort between 2004 and 2013. AF was identified in 1,662 patients, and 979 patients had preexisting AF before AIS. The annual proportion of patients with AIS with AF gradually increased from 13.4% to 22.6% over the study period (p for trends <0.001). Only 14.0% of patients with high risk AF were receiving OAC before the stroke, and this proportion remained relatively constant during the study period. However, the proportion of patients treated with antiplatelet agents had increased from 18.8% in 2004 to 45.3% in 2013, while that of patients receiving no antithrombotic agent decreased from 64.6% in 2004 to 43.9% in 2013. As a limitation, no information was available about non-vitamin K antagonist oral anticoagulants, because they were widely used since late 2014 in Korea. Conclusions: The number of patients with AIS and AF has steadily increased over the last 10 years in Korea. However, a small portion of patients with AF were receiving OAC therapy before the stroke and about half of the patients did not receive any antithrombotic medication. Our study demonstrates that there is huge gap between clinical practice and treatment guidelines for patients with AF in Korea. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). Material and methods: A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. Results: The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. Conclusions: Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk. [ABSTRACT FROM AUTHOR]

Background: A combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy. Objectives: Whether the treatment quality of warfarin measured by iTTR (individual time within therapeutic INR range) is associated with bleeding complications during triple therapy after PCI. Methods: A retrospective register study consisting of 601 triple treated PCI patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The cohort was cross-matched with the Swedish Patient Registry for background characteristics and bleeding complications up to 6 months after PCI using ICD10 codes, the Prescribed Drug Registry for ongoing medications, and the national oral anticoagulation registry Auricula for warfarin treatment quality. The patients were grouped into four iTTR groups: <50%, 50–69.9%, 70–84.9% and >85% as well as iTTR above or below 70%. Results: Of 601 patients, 39 (6.5%) had a bleeding complication (type 2 according to BARC). Bleeding was more common for iTTR<70% compared to iTTR>70%, 28 (9.3%) vs. 11 (3.7%) (p = 0.005). The bleeding frequency increased gradually from the best group, iTTR>85% with four bleeders (3.3%) up to 17 bleeders (13.3%) in the worst group with iTTR<50% (p = 0.003), with a corresponding bleeding rate per 100 treatment years of 8.0 and 44.9, respectively. In multivariate analysis low BMI, HR 1.11 (95% CI 1.01–1.22), a medical history of anemia HR 3.17 (1.16–8.69) and iTTR < 70% HR 2.86 (1.25–6.53) increased the risk of bleeding. Conclusion: Triple therapy after PCI confers a high risk of bleeding events. Warfarin treatment quality measured by iTTR as well as a medical history of anemia are strong independent predictors of bleeding in these patients. Physicians should pay more attention to iTTR after PCI. [ABSTRACT FROM AUTHOR]

Background: An increasing number of people are living with multiple chronic conditions and it is unclear which quality indicators should be used to guide care for this population. Objective: To critically appraise and select the most appropriate set of quality indicators for ambulatory care for older adults with five selected disease combinations. Methods: A two-round web-based Delphi process was used to critically appraise and select quality of care indicators for older adults with diabetes and comorbidities. A fifteen-member Canadian expert panel with broad geographical and clinical representation participated in this study. The panel evaluated process indicators for meaningfulness, potential for improvements in clinical practice, and overall value of inclusion, while outcome indicators were evaluated for importance, modifiability and overall value of inclusion. A 70% agreement threshold was required for high consensus, and 60–69% for moderate consensus as measured on a 5-point Likert type scale. Results: Twenty high-consensus and nineteen medium-consensus process and outcome indicators were selected for assessing care for older adults with selected disease combinations, including 1) concordant (conditions with a common management plan), 2) discordant (conditions with unrelated management plans), and 3) both types. Panelists reached rapid consensus on quality indicators for care for older adults with concordant comorbid conditions, but not for those with discordant conditions. All selected indicators assess clinical aspects of care. The feedback from the panelists emphasized the importance of developing indicators related to patient-centred aspects of care, including patient self-management, education, patient-physician relationships, and patient’s preferences. Conclusions: The selected quality indicators are not intended to provide a comprehensive tool set for measuring quality of care for older adults with selected disease combinations. The recommended indicators address clinical aspects of care and can be used as a starting point for ambulatory care settings and development of additional quality indicators. [ABSTRACT FROM AUTHOR]

The risk of thromboembolisms during the post-cardioversion period is high. For patients with persistent atrial fibrillation (AF), anticoagulation with warfarin (INR 2.0~3.0) is recommended for at least three weeks prior and four weeks after cardioversion. We aimed to evaluate the efficacy of apixaban in preventing thromboembolic events during post-cardioversion. We enrolled 127 consecutive persistent AF patients (83 persistent, 44 longstanding persistent AF), scheduled to undergo cardioversion and were pretreated with apixaban. All patients underwent transesophageal echocardiography (TEE) to rule out thrombi in the left atrium (LA) or LA appendage (LAA) after anticoagulation with apixaban. The median duration of anticoagulation before the TEE was 37 (interquartile range [IQR] 34, 50) days. There were 7 patients (5.5%) with visible thrombi in the LAA. A spontaneous echo contrast was noted in 24 (18.9%) patients. Cardioversion was attempted in 117 patients, and they were prescribed amiodarone before the elective DC cardioversion. Sinus rhythm was achieved in 37 patients (31.6%) by amiodarone itself. DC cardioversion was attempted in 80 patients and was successful in 73 (91.3%). None of the cardioverted patients had any thromboembolic events within one month. Transient ischemic attacks were observed in one patient during a median follow up period of 202 days (IQR 143, 294). In conclusion, apixaban could be used as an anticoagulant for patients scheduled for cardioversion. However, the incidence of thrombi was not negligible. TEE or other imaging modalities should be considered before cardioversion or other invasive procedures. [ABSTRACT FROM AUTHOR]

Objectives: To quantify changes in anticoagulant use in Australia since the introduction of Non-vitamin K antagonist anticoagulants (NOACs) and to estimate government expenditure. Design: Interrupted-time-series analysis quantifying anticoagulant dispensing, before and after first Pharmaceutical Benefits Scheme (PBS) NOAC listing in August 2009 for venous thromboembolism prevention; and expanded listing for stroke prevention in non-valvular atrial fibrillation (AF) in August 2013, up to June 2016. Estimated government expenditure on PBS-listed anticoagulants. Setting and participants: PBS dispensing in 10% random sample of Australians, restricted to continuous concessional beneficiaries dispensed oral anticoagulants from July 2005 to June 2016. Total PBS anticoagulant expenditure was calculated using Medicare Australia statistics. Main outcome measures: Monthly dispensing and initiation of oral anticoagulants (warfarin, rivaroxaban, dabigatran or apixaban). Annual PBS anticoagulant expenditure. Results: An estimated 149,180 concessional beneficiaries were dispensed anticoagulants (100% warfarin) during July 2005. This increased to 292,550 during June 2016, of whom 47.0%, 27.1%, 18.7% and 7.2% were dispensed warfarin, rivaroxaban, apixaban and dabigatran, respectively. Of 16,500 initiated on anticoagulants in June 2016, 24.3%, 38.2%, 30.0% and 7.5% were initiated on warfarin, rivaroxaban, apixaban, and dabigatran, respectively. Compared to July 2005-July 2013, from August 2013-June 2016, dispensings for all anticoagulants increased by 2,303 dispensings/month (p<0.001, 95%CI = [1,229 3,376]); warfarin dispensing decreased by 1,803 dispensings/month (p<0.001, 95%CI = [–2,606, –1,000]). Total PBS anticoagulant expenditure was $19.5 million (97.0% concessional) in 2008/09, of which 100% was warfarin and $203.3 million (86.2% concessional) in 2015/16, of which 11.2% was warfarin. Conclusions: The introduction of the NOACs led to substantial increases in anticoagulant use and expenditure in Australia. [ABSTRACT FROM AUTHOR]

Nattokinase is a fibrinolytic enzyme identified and isolated in 1987 from a specific Japanese food called natto (a kind of vegetable cheese). Since its discovery and until now, nattokinase has been studied experimentally and clinically almost exclusively in Japan, China, Korea and other countries in the respective geographical area, resulting in a complex picture of potentially useful properties in clinical practice. Nattokinase was approved for use in Europe in 2016 by EFSA (European Food Safety Authority) as a food supplement. [ABSTRACT FROM AUTHOR]

Objective: This study evaluates the actual blood pressure control rate and its estimation by general practitioners, the use of single-pill or free combinations, and the attitude towards single-pill combinations in primary care. Methods: Cross-sectional observational survey in primary care between January 2015 and September 2016 in Belgium and Luxembourg. The participating general practitioners enrolled hypertensive patients taking at least 2 antihypertensive molecules (as fixed or free associations). Results: 742 general practitioners included a total of 8,006 patients, with a mean age of 66 ± 12 years. Systolic blood pressure and diastolic blood pressure were respectively 141 ± 17 mmHg and 82 ± 10 mmHg (means ± SD). These patients had a blood pressure control rate of 45%, whereas it was estimated by general practitioners to be 60%. General practitioners with 11–25 years’ experience performed better than general practitioners with 36–51 years’ experience in the evaluation of blood pressure control. Combinations used were free in 39%, single-pill in 34% and mixed in 27% of the patients. Patients receiving single-pill combinations were younger than those treated with free combinations (63 ± 12 vs. 68 ± 12 years, p < 0.001), with fewer comorbidities (39 vs. 55%, p < 0.001). In patients treated solely with free pill associations, 66% of patient cases, general practitioners were willing to switch to a single-pill combination. The main reasons were improved adherence (76%) and better blood pressure control (64%). Conclusion: In patients requiring at least two antihypertensive drugs, blood pressure control rate remains low and is overestimated by general practitioners. Free combinations remain largely used although many general practitioners seem willing to shift to single-pill combinations. Treatment simplification could improve adherence and blood pressure control rate, which has been shown to lead to reduced morbidity and mortality. [ABSTRACT FROM AUTHOR]

Patients discharged on oral anticoagulant (OAC) therapy after percutaneous coronary intervention (PCI) represent a complex population and are at higher risk of early readmission. The reasons and predictors of early readmission in this group have not been well characterized. We identified patients in an integrated health care system who underwent PCI between 2009 and 2014 and were readmitted within 30 days within this health care system. Of the 9,357 patients surviving to discharge after the index PCI, 692 were readmitted within 30 days (7.4%). At the time of readmission, 143 had been discharged from the index PCI hospitalization on OACs (96.5% on warfarin) and 549 had not been discharged on OACs, with readmission rates of 12.9% and 6.7%, respectively (p<0.01). The most common reason for readmission among all patients was chest pain syndromes (21.7% on OACs, 34.4% not on OACs). However, bleeding represented the next most frequent cause of readmission among patients on OACs (14.0% on OACs vs 6.0% not on OACs, p<0.01). Among patients on OAC therapy, peripheral arterial disease (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.07–2.57, p = 0.02) and nonelective PCI (OR 1.91, 95% CI 1.17–3.12, p<0.01) were found to be independent predictors of 30-day readmission. During rehospitalization, compared to patients not on OACs, patients on OACs suffered a higher unadjusted rate of mortality (6.3% vs 1.8%, p<0.01) and a longer length of stay (6.4 ± 7.1 days vs 4.9 ± 6.8 days, p = 0.02). In conclusion, patients discharged on OAC therapy after PCI are commonly readmitted, with bleeding representing a major reason. These readmissions are associated with high mortality and longer lengths of stay. Interventions targeted towards optimizing discharge planning for these complex patients are needed to potentially reduce readmissions. [ABSTRACT FROM AUTHOR]

Introduction: Bleeding is a common complication in patients taking warfarin. We sought to compare the performance of nine prediction models for bleeding risk in warfarin-treated Brazilian outpatients. Methods: The dataset was derived from a clinical trial conducted to evaluate the efficacy of an anticoagulation clinic at a public hospital in Brazil. Overall, 280 heart disease outpatients taking warfarin were enrolled. The prediction models OBRI, Kuijer et al., Kearon et al., HEMORR2HAGES, Shireman et al., RIETE, HAS-BLED, ATRIA and ORBIT were compared to evaluate the overall model performance by Nagelkerke’s R2 estimation, discriminative ability based on the concordance (c) statistic and calibration based on the Hosmer-Lemeshow goodness-of-fit statistic. The primary outcomes were the first episodes of major bleeding, clinically relevant non-major bleeding and non-major bleeding events within 12 months of follow-up. Results: Major bleeding occurred in 14 participants (5.0%), clinically relevant non-major bleeding in 29 (10.4%), non-major bleeding in 154 (55.0%) and no bleeding at all in 115 (41.1%). Most participants with major bleeding had their risk misclassified. All the models showed low overall performance (R2 0.6–9.3%) and poor discriminative ability for predicting major bleeding (c <0.7), except Shireman et al. and ORBIT models (c 0.725 and 0.719, respectively). Results were not better for predicting other bleedings. All models showed good calibration for major bleeding. Conclusions: Only two models (Shireman et al. and ORBIT) showed at least acceptable performance in the prediction of major bleeding in warfarin-treated Brazilian patients. Accurate models warrant further investigation to be used in similar populations. [ABSTRACT FROM AUTHOR]

Objective: The correlation of depleted blood through midline shift in acute subdural hematoma remains the most reliable clinical predictor to date. On the other hand, patient’s ABO blood type has a profound impact on coagulation and hemostasis. We conducted this study to evaluate the role of patient’s blood type in terms of incidence, clinical course and outcome after acute subdural hematoma bleeding. Methods: 100 patients with acute subdural hematoma treated between 2010 and 2015 at the author’s institution were included. Baseline characteristics and clinical findings including Glasgow coma scale, Glasgow outcome scale, hematoma volume, rebleeding, midline shift, postoperative seizures and the presence of anticoagulation were analyzed for their association with ABO blood type. Results: Patient’s with blood type O were found to have a lower midline shift (p<0.01) and significantly less seizures (OR: 0.43; p<0.05) compared to non-O patients. Furthermore, patients with blood type A had the a significantly higher midline shift (p<0.05) and a significantly increased risk for postoperative seizures (OR: 4.01; p<0.001). There was no difference in ABO blood type distribution between acute subdural hematoma patients and the average population. Conclusion: The ABO blood type has significant influence on acute subdural hematoma sequelae. Patient’s with blood type O benefit in their clinical course after acute subdural hematoma whereas blood type A patients are at highest risk for increased midline shift and postoperative seizures. Further studies elucidating the biological mechanisms of blood type depended hemostaseology and its role in acute subdural hematoma are required for the development of an appropriate intervention. [ABSTRACT FROM AUTHOR]

Background: Small randomized controlled studies and meta-analyses have shown that thrombolysis, especially catheter-directed thrombolysis, can reduce the incidence of post-thrombotic syndrome (PTS). However, the recent ATTRACT trial did not demonstrate the same effects. Given this confusing situation, we performed an updated meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of thrombolysis, especially catheter-directed thrombolysis, on the outcomes of deep venous thrombosis (DVT). Methods: We searched PubMed, Embase, and the Cochrane Library for relevant studies comparing thrombolysis in combination with anticoagulation and with anticoagulation alone. The primary endpoint was PTS during the longest follow-up period. The safety endpoint was the incidence of major bleeding events. We also evaluated the outcomes of catheter-directed thrombolysis as a subgroup analysis. Results: Six RCTs, including 1418 patients with DVT, were included in our meta-analysis. Thrombolysis in combination with anticoagulation did not reduce PTS (RR: 0.90, [0.80–1.01], P = 0.19) and increased major bleeding (RR: 2.07, [1.12–3.81], P = 0.02). However, trial sequential analysis (TSA) showed that more patients are needed to support the conclusion that thrombolysis in combination with anticoagulation increased major bleeding. Catheter-directed thrombolysis did not reduce the incidence of PTS (RR: 0.88, [0.68–1.13], P = 0.31) and did increase the incidence of major bleeding events (RR: 1.89, [1.00–3.59], P = 0.05). Conclusion: Thrombolysis, including catheter-directed thrombolysis, did not reduce the incidence of PTS and increased the incidence of major bleeding. However, the results were not supported by TSA and sensitivity analysis, so more relevant studies are needed. [ABSTRACT FROM AUTHOR]

Background: No scores presently exist to predict bleeding in atrial fibrillation (AF) populations using direct oral anticoagulants (DOACs). We used data from two independent healthcare claims databases to develop and validate a predictive model of major bleeding in a contemporary AF population. Methods: Patients with non-valvular AF initiating oral anticoagulation were identified in the MarketScan databases from 2007–2014. Using Cox regression models in 1000 bootstrapped samples, we developed a model that selected variables predicting major bleeding in the first year after anticoagulant initiation. The final model was validated in patients with non-valvular AF in the Optum Clinformatics database in the period 2009–2015. The discriminative ability of existing bleeding scores were individually evaluated and compared with the new bleeding model termed Anticoagulation-specific Bleeding Score (ABS) in both MarketScan and Optum. Results: Among 119,083 patients with AF initiating oral anticoagulation in the derivation cohort, 4,030 experienced a bleeding event. The variable selection model identified 15 variables (including individual type of oral anticoagulant) associated with major bleeding. Discrimination of the model was modest [c-statistic 0.68, 95% confidence interval (CI) 0.67–0.69]. The model was subsequently applied to 81,285 AF patients in the validation data set (3,238 bleeding events), showing similar discrimination (c-statistic 0.68, 95% CI 0.67–0.69). In both cohorts, the predictive performance of the ABS was better than the existing models for bleeding prediction in AF. Conclusions: We developed a model that uses administrative healthcare data for the identification of AF patients at higher risk of bleeding after initiation of oral anticoagulation, taking into account the lower bleeding risk in DOAC compared to warfarin users. [ABSTRACT FROM AUTHOR]

Background: Anticoagulant therapy is recommended in patients with atrial fibrillation (AF) but remains underused. The proper use of anticoagulants has been encouraged in guidelines frequently published over the past two decades. Materials and methods: In this study, we used insurance claims data collected from 2005 to 2014 to investigate the prevalence and incidence of non-valvular AF (NVAF) patients aged 20 to 74 years standardized to the Japanese population in 2012 and subdivided by stroke prevention drug type. We estimated the frequency of coagulation monitoring in patients with incident NVAF undergoing warfarin therapy in 2011 and later. Results: From 2005 to 2014, the standardized prevalence of NVAF increased from 117/100,000 to 278/100,000 and the proportion of anticoagulant users increased from 38.4% to 58.0%, while that of antiplatelet monotherapy decreased from 32.3% to 12.0%. The standardized incidence of NVAF was stable at ~40/100,000 patient-years. The proportion of those patients who started anticoagulant soon after the initial diagnosis increased from 19.9% to 49.1% from 2006 to 2013. Among patients who started warfarin, switchers to DOAC had more frequent coagulation monitoring than non-switchers. Conclusion: The use of anticoagulant therapy has gradually increased in patients with NVAF in Japan during the study period from 2005 to 2014. [ABSTRACT FROM AUTHOR]