Antithrombotic treatments in patients with chronic coronary artery disease or peripheral artery disease: a systematic review of randomised controlled trials

Aims: Acetylsalicylic acid (ASA) is widely used for the prevention of atherothrombotic events in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), but the risk of vascular events remains high. We aimed at identifying randomised controlled trials (RCTs) on antithrombotic treatments in patients with chronic CAD or PAD. Methods: Searches were conducted on MEDLINE, EMBASE, and CENTRAL on March 1st, 2018. This systematic review (SR) uses a narrative synthesis to summarize the evidence for the efficacy and safety of antiplatelet and anticoagulant therapies in the population of both chronic CAD or PAD patients. Results: Four RCTs from 27 publications were included. Study groups included 15,603 to 27,395 patients. ASA alone was the most extensively studied (); other studies included rivaroxaban with or without ASA (), vorapaxar alone (), and clopidogrel with () or without ASA (). Clopidogrel alone and clopidogrel plus ASA compared to ASA presented similar efficacy with comparable safety profile. Rivaroxaban plus ASA significantly reduced the risk of the composite of cardiovascular death, myocardial infarction, and stroke compared to ASA alone, although major bleeding with rivaroxaban plus ASA increased. Conclusion: There is limited and heterogeneous evidence on the prevention of atherothrombotic events in patients with chronic CAD or PAD. Clopidogrel alone and clopidogrel plus ASA did not demonstrate superiority over ASA alone. A combination of rivaroxaban plus ASA may offer significant additional benefit in reducing cardiovascular outcomes, yet it may increase the risk of bleeding, compared to ASA alone

Efficacy and safety of rivaroxaban compared with other therapies used in patients with peripheral artery disease undergoing peripheral revascularization: a systematic literature review and network meta-analysis

Background. The guidelines on antithrombotic treatment in patients with symptomatic peripheral artery disease (PAD) undergoing peripheral revascularization of the lower extremities were developed based on heterogeneous trials, assessing various dose regimens and recruiting patients who were subjected to different revascularization procedures. Objective. To compare efficacy and safety of treatments used in patients with PAD undergoing peripheral revascularization accounting for between-trial heterogeneity and large dispersion of the quality of evidence. Methods. A systematic literature review of randomised controlled trials (RCTs) recruiting adult patients with PAD receiving antithrombotics was conducted until January 2020. Hazard ratios (HR) were pooled using Bayesian network meta-analysis. The estimated between-treatment effects were presented as HR together with 95% credible intervals. The base case analysis included studies recruiting patients following recent peripheral revascularization, who received treatment regimens administered within the recommended therapeutic window, while a sensitivity scenario included all identified trials. Results. Thirteen RCTs were identified (8 RCTs enrolled patients following peripheral revascularization and 5 RCTs regardless of the previous revascularization). Five trials, recruiting an overall of 8349 patients, were considered for the base case analysis. Of those, 6564 patients were recruited in the VOYAGER PAD trial comparing rivaroxaban plus aspirin (RIV plus ASA) versus ASA. RIV plus ASA was associated with a lower risk of repeated peripheral revascularization versus ASA monotherapy ( [0.79, 0.99]), however having a trend towards an increased rate of major bleeding ( [0.98, 2.11]). There was no evidence for differences between RIV plus ASA and dual antiplatelet therapy and vitamin K antagonists plus ASA. Similar results were observed in sensitivity analyses. Conclusions. RIV plus ASA is associated with reduced risk of revascularization compared with ASA monotherapy, but the evidence for other comparators, in particular antiplatelet regimens, was insufficient to guide treatment decisions and highlights the challenge in establishing the magnitude of comparative efficacy using existing RCTs

SPLURGE: Scholars Portal Library Usage-Based Recommendation Generation Engine

We will outline the birth and delivery of SPLURGE (Scholars Portal Library Usage-based Recommendation Generation Engine). SPLURGE came about as an idea to build up a book title recommendation service by pooling circulation data from university libraries in the province of Ontario. Following the precedent of a project that was launched by the Joint Information Systems Committee (JISC) in the United Kingdom, a group of Systems folks in Ontario met and surmised it would be interesting to start collecting circulation data that could then be fed back into the school’s various catalogue interfaces. The data would make it possible to provide context-sensitive book suggestions, to researchers, in the search results: in the manner Amazon or EBay recommends items for purchase to its shoppers.Following the launch of a GitHub site for the project and armed with only a rough outline of the goals, over twenty five people from sixteen institutions gathered for a single hackfest event to explore and discuss the possible paths to further bring SPLURGE into fruition. Is this another add-on that will serve to simply spoon-feed our users? Or, will SPLURGE zestfully put the dip back into serendipity for those researchers who might have otherwise not connected potential resources in their initial catalogue queries? How too, might such a tool be used to aid in a Library’s collection development? All in all, it’s going to be a tool that lets you question the answers. We’ll show how it works, how we built it, how you can use it, and where it could go

Use of real-world evidence in meta-analyses and cost-effectiveness models

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial data with valuable information on patient behaviors and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges. The objectives of this communication were to (1) summarize all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses. No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results. RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines

Burden of coronary artery disease and peripheral artery disease: a literature review

Background. Atherothrombotic disease, including coronary artery disease (CAD) and peripheral artery disease (PAD), can lead to cardiovascular (CV) events, such as myocardial infarction, stroke, limb ischemia, heart failure, and CV death. Aim. Evaluate the humanistic and economic burden of CAD and PAD and identify unmet needs through a comprehensive literature review. Methods. Relevant search terms were applied across online publication databases. Studies published between January 2010 and August 2017 meeting the inclusion/exclusion criteria were selected; guidelines were also included. Two rounds of screening were applied to select studies of relevance. Results. Worldwide data showed approximately 5–8% prevalence of CAD and 10–20% prevalence of PAD, dependent on the study design, average age, gender, and geographical location. Data from the REACH registry indicated that 18–35% of patients with CAD and 46–68% of patients with PAD had disease in one or more vascular beds. Use of medication to control modifiable CV risk factors was variable by country (lower in France than in Canada); statins and aspirin were the most widely used therapies in patients with chronic disease. Survival rates have improved with medical advancements, but there is an additional need to improve the humanistic burden of disease (i.e., associated disability and quality of life). The economic burden of atherothrombotic disease is high and expected to increase with increased survival and the aging population. Conclusion. CAD and PAD represent a substantial humanistic and economic burden worldwide, highlighting a need for new interventions to reduce the incidence of atherothrombotic disease

Real-world cost-effectiveness of rivaroxaban and apixaban vs VKA in stroke prevention in non-valvular atrial fibrillation in the UK

International audienceBackground: Morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) imposes a substantial economic burden on the UK healthcare system. Objectives: An existing Markov model was adapted to assess the real-world cost-effectiveness of rivaroxaban and apixaban, each compared with a vitamin K antagonist (VKA), for stroke prevention in patients with NVAF from the National Health Service (NHS) and personal and social services (PSS) perspective. Methods: The model considered a cycle length of 3 months over a lifetime horizon. All inputs were drawn from real-world evidence (RWE): baseline patient characteristics, clinical event and persistence rates, treatment effect (meta-analysis of RWE studies), utility values and resource use. Deterministic and probabilistic sensitivity analyses were performed. Results: The incremental cost per quality-adjusted life year was £14,437 for rivaroxaban, and £20,101 for apixaban, compared with VKA. The probabilities to be cost-effective compared with VKA were 90% and 81%, respectively for rivaroxaban and apixaban, considering a £20,000 threshold. In both comparisons, the results were most sensitive to clinical event rates. Conclusions: These results suggest that rivaroxaban and apixaban are cost-effective vs VKA, based on RWE, considering a £20,000 threshold, from the NHS and PSS perspective in the UK for stroke prevention in patients with NVAF. This economic evaluation may provide valuable information for decision-makers, in a context where RWE is more accessible and its value more acknowledged

Systematic Literature Review of Randomized Trials Comparing Antithrombotic Therapy Following Revascularization Procedures in Patients With Peripheral Artery Disease.

A systematic literature review was conducted to identify and summarize the clinical efficacy and safety of available antithrombotic therapies after peripheral endovascular or surgical revascularization in patients with peripheral artery disease (PAD). Five databases were searched using free-text and Emtree/Mesh terms for PAD, randomized controlled trials (RCTs), and antithrombotic therapies of interest (ie, single antiplatelet therapy, dual antiplatelet therapy, and vitamin K antagonists). Randomized controlled trials were eligible for inclusion if they assessed the risk of thrombotic events (ie, myocardial infarction, ischemic stroke, cardiovascular death, limb ischemia, or limb amputation) or safety profile (ie, minor, moderate, major, or fatal bleeding events) after revascularization. In total, 16 RCTs were identified. Only a few studies reported on treatment effects of the investigated therapies. Myocardial infarction, ischemic stroke, cardiovascular death, and amputation were reported in up to 2.3%, 2.3%, 5.6%, and 7.3% of patients, respectively. Bleeding events were observed in up to 8.4% (major) and 1.5% (fatal) of patients. Despite available treatments, patients with PAD undergoing revascularization remain at risk of thrombotic events. There is a need for new treatments that will help to optimize care for patients with symptomatic PAD undergoing revascularization

Estimation of the costs attributable to vitamin K antagonist treatment in patients with non-valvular atrial fibrillation from a French societal perspective

Background: Little is known about the costs associated with vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (NVAF) in France. Objectives: To evaluate monthly per-patient costs attributable to VKA treatment in NVAF patients from a French societal perspective. Study design: Retrospective data were obtained from 7 international normalised ratio (INR) monitoring centres in France. Patients older than 18 years of age with NVAF treated with VKA were recruited. Additional patient-level data assessing resource use corresponding with VKA treatment were collected via self-completed questionnaires. Unit costs applicable to 2015 were multiplied by resource use and summed to generate VKA treatment costs. Results: 363 patients were included; 53% were men. The majority of patients received fluindione (72%). The number of INR tests per patient per month was 1.69 (95% CI, 1.59–1.80). The monthly patient cost was €39.72 (€36.23–43.21) from the French societal perspective. Direct medical costs comprised 76% of overall costs, with drug costs representing 7.4% (€2.4); direct non-medical and indirect costs comprised 10% and 14% respectively. Conclusions: Costs associated with VKA treatment in NVAF cannot be estimated only with drug costs. When direct and indirect attributable costs associated with VKA treatment are considered, the VKA treatment costs are more substantial