The cost-effectiveness and monetary benefits of dabigatran in the prevention of arterial thromboembolism for patients with non-valvular atrial fibrillation in the Netherlands

BACKGROUND: Atrial fibrillation (AF) causes a significant health and economic burden to the Dutch society. Dabigatran was proven to have at least similar efficacy and a similar or better safety profile when compared to vitamin K antagonists (VKAs) in preventing arterial thromboembolism in patients with AF. OBJECTIVE: To evaluate the cost-effectiveness and monetary benefit of dabigatran versus VKAs in Dutch patients with non-valvular AF. Value-based pricing considerations and corresponding negotiations on dabigatran will be explicitly considered. METHODS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the RE-LY trial and Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. RESULTS: Dabigatran was cost saving compared to VKAs. A total of 4,552 QALYs were gained and €13,892,288 was saved in a cohort of 10,000 AF patients. The economic value of dabigatran was strongly related to the costs of VKA control that are averted. Notably, dabigatran was cost saving compared to VKAs if annual costs of VKA control exceeded €159 per person or dabigatran costs were below €2.81 per day. CONCLUSION: Dabigatran was cost saving compared to VKAs for the prevention of atrial thromboembolism in patients with non-valvular AF in the Netherlands. This result appeared robust in the sensitivity analysis. Furthermore, volume based reduction of the price in the Netherlands will further increase the monetary benefits of dabigatran

Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands

BACKGROUND: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.OBJECTIVE: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands.METHODS: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER).RESULTS: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust.CONCLUSIONS: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.</p

Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination

Aims To assess the yield of screening for atrial fibrillation (AF) with a hand-held single-lead electrocardiogram (ECG) device during influenza vaccination in primary care in the Netherlands. Methods and results We used the MyDiagnostick to screen for AF in persons who participated in influenza vaccination sessions of ten Dutch primary care practices. In case of suspected AF detection by the stick, the recorded 1-min ECG registrations were analysed by a cardiologist. We scrutinized electronic medical files of the general practitioners to obtain information about the cases screened. Multivariable logistic regression analysis was performed to predict the relation between patient characteristics and a new screen-detected diagnosis of AF. In total, 3269 persons were screened for AF during the influenza vaccination sessions of 10 general practitioner practices. As a result, 37 (1.1%) new cases of AF were detected. Prior transient ischeamic attack or stroke (OR 6.05; 95%CI 1.93-19.0), and age (OR 1.09 per year; 95% CI 1.05-1.14) were independent predictors for such newly screen-detected AF. Of the 37 screen-detected AF cases, 2.7% had a CHA2DS2-VASc of 0, 18.9% a score of 1, and 78.4% a score of 2 or more. The majority needed oral anticoagulant therapy. Conclusions Screening seems feasible with an easy to use single-lead, hand-held ECG device with automatic AF detection during influenza vaccination in primary care and results in a '1-day' yield of 1.1% new cases of AF. Trial registration clinicaltrials.gov NCT02006524

Incidence, treatment and mortality of new-onset atrial fibrillation patients at the intensive care unit

Objective Critically ill patients admitted to the intensive care unit (ICU) often develop atrial fibrillation (AF), with an incidence of around 5%. Stroke prevention in AF is well described in clinical guidelines. The extent to which stroke prevention is prescribed to ICU patients with AF is unknown. We aimed to determine the incidence of new-onset AF and describe stroke prevention strategies initiated on the ICU of our teaching hospital. Also, we compared mortality in patients with new-onset AF to critically ill patients with previously diagnosed AF and patients without any AF. Methods This study was a retrospective cohort study including all admissions to the ICU of the Martini Hospital (Groningen, The Netherlands) in the period 2011 to 2016. Survival analyses were performed using these real-world data. Results In total, 3334 patients were admitted to the ICU, of whom 213 patients (6.4%) developed new-onset AF. 583 patients (17.5%) had a previous AF diagnosis, the other patients were in sinus rhythm. In-hospital mortality and 1-year mortality after hospital discharge were significantly higher for new-onset AF patients compared with patients with no history of AF or previously diagnosed AF. At hospital discharge, only 56.3% of the new-onset AF-patients eligible for stroke prevention received an anticoagulant. Anticoagulation was not dependent on CHA 2DS 2-VASc score or other patient characteristics. An effect of anticoagulative status on mortality was not significant. Conclusion AF is associated with increased mortality in critically ill patients admitted to the ICU. More guidance is needed to optimise anticoagulant treatment in critically ill new-onset AF patients

Atrial Fibrillation in Africa-An Underreported and Unrecognized Risk Factor for Stroke:A Systematic Review

Over three-quarters of deaths from cardiovascular disease and diabetes occur in low- and middle-income countries, which include many African countries. Global studies showed that the prevalence of the cardiac arrhythmia atrial fibrillation (AF) appeared to be lower in Africa. A systematic search of PubMed and African Journals Online was conducted to determine the prevalence of AF and associated stroke risk factors in Africa and to quantify the need for screening. The publications search yielded a total of 840 articles of which 41 were included. AF was often not identified as the disease of primary interest with its own risks. Data on prevalence in the general population was scarce. The prevalence of stroke risk factors showed a large variation between studies, as well as within clustered subpopulations. AF in Africa is under-reported in published reports. The study types and populations are highly heterogeneous, making it difficult to draw a definitive conclusion on AF prevalence

Does growth rate determine the rate of metabolism in shorebird chicks living in the arctic?

We measured resting and peak metabolic rates (RMR and PMR, respectively) during development of chicks of seven species of shorebirds: least sandpiper (Calidris minutilla; adult mass 20 22 g), dunlin (Calidris alpina; 56-62 g), lesser yellowlegs (Tringa flavipes; 88-92 g), short-billed dowitcher (Limnodromus griseus; 85-112 g), lesser golden plover (Pluvialis dominicana; 150-156 g), Hudsonian godwit (Limosa haemastica; 205-274 g), and whimbrel (Numenius phaeopus; 380 g). We tested two opposing hypotheses: the growth rate-maturity hypothesis, which posits that growth rate in chicks is inversely related to functional maturity of tissues, and the fast growth rate-high metabolism hypothesis, which suggests that rapid growth is possible only with a concomitant increase in either RMR or PMR. We have found no evidence that chicks of shorebirds with fast growth rates have lower RMRs or lower PMRs, as would be predicted by the growth rate-maturity hypothesis, but our data suggested that faster-growing chest muscles resulted in increased thermogenic capacity, consistent with the fast growth-high metabolism hypothesis. The development of homeothermy in smaller species is a consequence primarily of greater metabolic intensities of heat-generating tissues. The maximum temperature gradient between a chick's body and environment that can be maintained in the absence of a net radiative load increased rapidly with body mass during development and was highest in least sandpipers and lowest among godwits. Chicks of smaller species could maintain a greater temperature gradient at a particular body mass because of their higher mass-specific maximum metabolic rates

Opportunistic screening versus usual care for diagnosing atrial fibrillation in general practice:a cluster randomised controlled trial

BackgroundAtrial fibrillation [AF] increases the risk of stroke, heart failure, and all-cause mortality. AF may be asymptomatic and therefore remain undiagnosed. Devices such as single-lead electrocardiographs [ECGs] may help GPs to diagnose AF.AimTo investigate the yield of opportunistic screening for AF in usual primary care using a single-lead ECG device.Design and settingA clustered, randomised controlled trial among patients aged &gt;= 65 years with no recorded AF status in the Netherlands from October 2014 to March 2016.MethodFifteen intervention general practices used a single-lead ECG device at their discretion and 16 control practices offered usual care. The follow-up period was 1 year, and the primary outcome was the proportion of newly diagnosed cases of AF.ResultsIn total. 17 107 older people with no recorded AF status were eligible to participate in the study. In the intervention arm. 10.7% of eligible patients [n = 919] were screened over the duration of the study year. The rate of newly diagnosed AF was similar in the intervention and control practices [1.43% versus 1.37%, P= 0.73]. Screened patients were more likely to have comorbidities, such as hypertension [60.0% versus 48.7%], type 2 diabetes [24.3% versus 18.6%], and chronic obstructive pulmonary disease [11.3% versus 7.4%], than eligible patients not screened in the intervention arm. Among patients with newly diagnosed AF in intervention practices. 27% were detected by screening, 23% by usual primary care. and 50% by a medical specialist or after stroke/transient ischaemic attack.ConclusionOpportunistic screening with a single-lead ECG at the discretion of the GP did not result in a higher yield of newly detected cases of AF in patients aged &gt;= 65 years in the community than usual care. For higher participation rates in future studies, more rigorous screening methods are needed.</p

Correction:Cost-effectiveness of apixaban compared to other anticoagulants in patients with atrial fibrillation in the real-world and trial settings

[This corrects the article DOI: 10.1371/journal.pone.0222658.]