Savings associated with surgical aortic valve replacement with a RESILIA tissue valve based on seven-year COMMENCE trial results.

BACKGROUND: Bioprostheses with RESILIA tissue demonstrate a reduction in calcification and improve health outcomes in pre-clinical and clinical studies. Prior economic analyses which relied on 5 years of evidence from the COMMENCE trial demonstrate financial savings for RESILIA tissue valves relative to mechanical valves after surgical aortic valve replacement (SAVR). Given the recent release of 7-year COMMENCE data, this economic evaluation updates the estimate for long-run savings of bioprosthetic valves with RESILIA. METHODS: Simulation models estimated disease progression across two hypothetical SAVR cohorts (tissue vs. mechanical) of 10,000 patients each in the US. The primary comparison calculated the SAVR-related expenditures associated with each valve type ($US, 2023). Health outcome probabilities were based on the COMMENCE trial though year 7 and projected for an additional 8 years based on prior studies of tissue and mechanical SAVR. Costs for key outcomes (mortality, reoperation, bleeding, thromboembolism, endocarditis) and anticoagulant monitoring were sourced from the literature. Incidence rates of health outcomes associated with mechanical valves relied on relative risks of tissue valve versus mechanical valve patients. RESULTS: Seven-year savings are $13,415 (95% CI = $10,472-$17,321) per patient when comparing RESILIA versus mechanical SAVR. Projected 15-year savings were $23,001 ($US, 2023; 95% CI = $17,802-$30,421). Most of the 15-year savings are primarily attributed to lower anti-coagulation monitoring costs ($21,073 in ACM savings over 15 years), but lower bleeding cost (savings: $2,294) and thromboembolism-related expenditures (savings: $852) also contribute. Reoperation and endocarditis expenditures were slightly larger in the RESILIA cohort. If reoperation relative risk reverts from 1.1 to 2.2 (the level in legacy tissue valves) after year 7, savings are $18,064. RESILIA SAVR also reduce costs relative to legacy tissue valves. CONCLUSION: Patients receiving RESILIA tissue valves are projected to have lower SAVR-related health expenditures relative to mechanical and legacy tissue valves.

Evaluation of the Effectiveness and Safety of Direct Oral Anticoagulants in Elderly Patients With Nonvalvular Atrial Fibrillation Who Are Not Candidates for Warfarin in Real-World Setting.

ABSTRACT: Limited literature has established the role of direct oral anticoagulants (DOAC) for elderly patients with nonvalvular atrial fibrillation who are unsuited for warfarin. Therefore, the objectives of this study were to assess the effectiveness and safety of DOAC use in this vulnerable patient population. This was a retrospective propensity score matching cohort study. Among all patients aged 75+ years who were not candidates for warfarin, we matched those who initiated DOAC between September 2017 and September 2018 with those who did not receive DOAC or warfarin in a 1:1 ratio. Effectiveness outcome was a composite measure of stroke, transient ischemic attack, and pulmonary embolism. Safety outcome was a composite measure of non-trauma-related intracranial hemorrhage and gastrointestinal bleed. Unless patients died or lost membership, follow-up period for the effectiveness outcome was until the end of 2019, whereas the safety outcome was for a period up to 1 year. Conditional logistic regression was used to analyze both outcomes. We identified 7818 patients who met the inclusion criteria and started DOAC, which matched to 7818 patients who did not receive anticoagulants. The mean age was 82.3 ± 5.1 years, and 51.5% male. The DOAC group had a lower hazard ratio of 0.37 (confidence interval, 0.24-0.57; P < 0.01) for composite effectiveness outcomes, whereas no difference in the composite safety outcome (hazard ratio, 0.91; confidence interval, 0.65-1.25; P = 0.55) when compared with matched control. In conclusion, DOAC was found to be effective in preventing thromboembolic events in patients aged 75+ years with nonvalvular atrial fibrillation who were not eligible for warfarin.

Advances in the management of atrial fibrillation with a special focus on non-pharmacological approaches to prevent thromboembolism: a review of current recommendations.

Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.

The atrial FibriLlatiOn real World management registry in the Middle East and Africa: design and rationale.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, affecting 33.5 million patients globally. It is associated with increased morbidity, leading to significant clinical and economic burden. There exist only limited data in the Middle Eastern region from the existing registries. The goal of the FLOW-AF (atrial FibriLlatiOn real World management registry in the Middle East and Africa) registry is to evaluate the characteristics, treatment patterns, and clinical and economic outcomes associated with anticoagulation among patients newly diagnosed with nonvalvular atrial fibrillation in Egypt, Lebanon, the Kingdom of Saudi Arabia, and the United Arab Emirates. METHODS: This study will be a multicountry, multicenter, prospective observational registry aiming to enroll 1446 newly diagnosed nonvalvular atrial fibrillation patients at more than 20 sites across the four countries. During the recruitment period, patients will be included if they were newly diagnosed with nonvalvular atrial fibrillation and had initiated treatment for the prevention of stroke/systemic embolism. Patient data will be assessed prospectively at 6 and 12 months from their enrollment date. Demographics, clinical characteristics, antithrombotic treatments received, clinical outcomes, adverse events, healthcare resource utilization, and direct costs associated with management of nonvalvular atrial fibrillation will be collected and analyzed overall, by country, and by groups created based on treatment, demographics, and clinical characteristics, medical history and risk factors. CONCLUSION: The FLOW-AF registry will provide information on the uptake of oral anticoagulants, treatment patterns, clinical outcomes, and healthcare utilization and costs among newly diagnosed nonvalvular atrial fibrillation patients in the Middle Eastern region.

Real-world, retrospective study evaluating thromboembolic events, associated risk factors, and health-care resource utilization in Japanese patients with polycythemia vera.

In this retrospective, real-world study, we used medical claims data to evaluate the incidence of thromboembolic events (TEs), time to TE, associated risk factors, and health-care resource utilization (HRU) in Japanese patients with polycythemia vera (PV; N = 606) from April 1, 2008, to August 31, 2015. Baseline characteristics of interest included median age, 67.0 years; previous TEs, 11.6%; cardiovascular conditions (CVCs), 45.7%; and ≥ 3 risk factors, 17.8%. Overall, 100 patients experienced TEs (118 events) at a rate of 8.15/100 person-years [TE-free survival rate, 69.3% (2008-2015)]. The annual total health-care costs [mean (per person)] were significantly impacted by the presence of TEs (yes vs. no: ¥993,000 vs ¥459,000; P < 0.001). These results confirm that the presence of CVCs increases the risk of TEs in Japanese patients with PV; occurrence of TEs was associated with a higher HRU in these patients.

New oral anti-coagulants versus vitamin K antagonists in high thromboembolic risk patients.

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.

Prophylactic Inferior Vena Cava Filters Prior to Bariatric Surgery: Insights From the National Inpatient Sample.

OBJECTIVES: The aim of this study was to determine in-hospital mortality, post-surgical thromboembolic events, and health care costs associated with the placement of prophylactic inferior vena cava filters (IVCFs) prior to bariatric surgery. BACKGROUND: The role of prophylactic IVCFs prior to bariatric surgery is controversial, and the nationwide clinical outcomes associated with this practice are unknown. METHODS: This observational study used the National Inpatient Sample database to identify obese patients who underwent bariatric surgery from January 2005 to September 2015. Using propensity score matching, outcomes associated with patients receiving prophylactic IVCFs prior to their bariatric surgery were compared with those among patients who did not receive IVCFs. RESULTS: A total of 258,480 patients underwent bariatric surgery, of whom 1,047 (0.41%) had prophylactic IVCFs implanted. Patients with prophylactic IVCFs compared with those without IVCFs had a significantly higher rate of the combined endpoint of in-hospital mortality or pulmonary embolism (1.4% vs. 0.4%; odds ratio: 3.75; 95% confidence interval [CI]: 1.25 to 11.30; p = 0.019). Additionally, prophylactic IVCFs were associated with higher rates of lower extremity or caval deep vein thrombosis (1.8% vs. 0.3%; odds ratio: 6.33; 95% CI: 1.87 to 21.4; p < 0.01), length of stay (median 3 days vs. 2 days; p < 0.01), and hospital charges (median $63,000 vs. $37,000; p < 0.01). CONCLUSIONS: In this nationwide observational study, prophylactic IVCF implantation prior to bariatric surgery was associated with worse clinical outcomes and increased health care resource utilization.

Economic burden of thromboembolic and hemorrhagic complications in non-valvular atrial fibrillation in Algeria (the ELRAGFA study).

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with substantial public health and economic impact on healthcare systems due to the prevention and management of thromboembolic and hemorrhagic complications. In Algeria, stroke is a leading cause of death, representing 15.6% of all deaths in 2012. Current data on the epidemiology and costs associated with non-valvular AF (NVAF) in Algeria are not available. METHODS: A three-step approach was undertaken to estimate the economic burden of NVAF in Algeria. First, a literature review identified the epidemiological burden of the disease. Second, expert clinicians practicing in Algerian hospitals were surveyed on consumed resources and unit costs of treatment and management of complications and prevention. Finally, these data were combined with event probabilities in an economic model to estimate the annual cost of NVAF prevention and complications for the Algerian healthcare system. RESULTS: Based on literature and demographics data, it was estimated that there are currently 187,686 subjects with NVAF in Algeria. Seventy per cent of this population was treated for prevention, half of which were controlled. Cost of prevention was estimated at 203 million DZD (€1.5 million) for drugs and 349 million DZD (€2.6 million) for examinations. Mean hospitalization costs for complications ranged between 123,500 and 435,500 DZD (€910-3,209), according to the type and severity of complications. Hospitalization costs for thromboembolic and hemorrhagic complications were estimated at 8,313 million DZD (€62 million), half of which was for untreated patients. Finally, the economic burden of NVAF was estimated at 8,865 million DZD (>€65 million) annually. CONCLUSION: The economic burden of NVAF is important in Algeria, largely driven by untreated and INR-uncontrolled patients. There is a lack of information on the Algerian healthcare system that could increase uncertainty around this assessment, but it clearly establishes the importance of NVAF as a public health concern.

Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

INTRODUCTION: Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. AREAS COVERED: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. EXPERT COMMENTARY: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

Health Care Costs and Thromboembolic Events in Hydroxyurea-Treated Patients with Polycythemia Vera.

BACKGROUND: Patients with polycythemia vera (PV) are at increased risk of thromboembolic events (TEs), which are key contributors to reduced overall survival compared with the age- and sex-matched general population. In addition to aspirin and phlebotomy to maintain hematocrit level < 45%, many patients receive cytoreduction with hydroxyurea (HU), which is associated with improved survival and may reduce the risk of cardiovascular events and TEs. However, 1 in 4 patients become resistant to or intolerant of HU. In the general population, prophylaxis and treatment following arterial and venous thromboses are associated with increased health care resource utilization and costs. OBJECTIVE: To describe the health care resource utilization and costs associated with TEs in patients with PV treated with HU in the United States. METHODS: This retrospective cross-sectional analysis of the Truven Health Analytics MarketScan Research Databases included adult patients with a PV diagnosis who were newly treated with HU and continuously enrolled in medical and pharmacy benefit plans for ≥ 12 months pre- and post-index. HU treatment administration, persistence, adherence, and related adverse events, as well as TEs, were reported during the 12-month follow-up period. HU treatment patterns were further analyzed in a subgroup analysis comparing patients with and without a ≥ 45-day gap in HU treatment. Health care resource utilization and costs were analyzed in a subgroup analysis comparing patients who had TEs in the 12-month follow-up period with those who did not. Tests for statistically significant differences across the comparison groups were conducted, including chi-square tests for categorical variables and t-tests for continuous variables. RESULTS: The records of 1,322 patients with PV were included in this study. Mean age was 66.0 years; 51.3% were men; and 14.0% had a history of TEs. During the first year of HU treatment, 764 (57.8%) patients had a treatment gap of ≥ 45 days; however, treatment adherence was similar between those with and those without a gap (85.2% vs. 90.7%, respectively). TEs occurred in 216 (16.3%) patients within 12 months of HU initiation. Health care resource utilization was higher for patients with TEs versus those without, including the proportion of patients requiring inpatient services (50.9% vs. 18.4%; P < 0.001) and emergency room visits (48.1% vs. 26.3%; P < 0.001) and the mean number of inpatient admissions (1.7 vs. 1.3; P = 0.004); office visits (18.9 vs. 14.1; P < 0.001); and prescriptions (45.8 vs. 36.2; P<0.001). In addition, total mean health care costs ($45,040 vs. $16,438; P < 0.001); inpatient costs ($18,952 vs. $4,794; P < 0.001); outpatient costs ($20,844 vs. $8,046; P < 0.001); and outpatient pharmacy costs ($5,244 vs. $3,598; P = 0.002) were higher among patients with TEs than those without. CONCLUSIONS: Patients with PV receiving treatment with HU remain at risk for TEs. The occurrence of TEs during the 12-month follow-up in this patient population was associated with higher health care resource utilization and costs. DISCLOSURES: This study was funded by Incyte Corporation. Parasuraman and Paranagama are employees and stockholders of Incyte Corporation. Shi and Bonafede are employees of Truven Health Analytics, which was awarded a research contract to conduct this study with and on behalf of Incyte Corporation. Study concept and design were contributed by all of the authors, who also interpreted the data and wrote and revised the manuscript. Bonafede and Shi collected the data. This study was presented as an abstract at the Academy of Managed Care Pharmacy NEXUS Annual Meeting on October 26-29, 2015, in Orlando, Florida.

Rivaroxaban vs. warfarin on extended deep venous thromboembolism treatment: A cost analysis.

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

World Health Organization and Essential Medicines.

In June 2017, the World Health Organization released 20th Model List of Essential Medicines for adults and sixth Model List of Essential Medicines for children. In our commentary, we describe the changes to the Essential Medicine list, and identify deficits in excluding medicines for management of diseases with a high burden. In using tracer conditions such as cardiovascular and thromboembolic disease, mental health, and diseases of the musculoskeletal system, we highlight the absence of several medicines, which are incorporated into major clinical practice guidelines. We recommend that the World Health Organization review its process with respect to identifying disease conditions as well as evidence-based therapies.

[Left atrial appendage closure and embolic events]. / Fermeture d'auricule et pathologie embolique.

Atrial fibrillation (AF) is frequent and responsible for embolic events. Currently, the gold standard to prevent such embolic events is anticoagulant therapy with vitamin K antagonist (VKA) or direct oral anticoagulant in nonvalvular AF. Recently, left atrial appendage closure was proposed as an alternative to anticoagulant inpatient with high embolic risk and contraindication to anticoagulant therapy. Data from randomized trials were consistent with a non-inferiority of left atrial appendage closure in comparison to VKA in terms of stroke and cardiovascular death. However, despite improvements in procedure results and complications reduction, this invasive strategy has to be performed with optimal security as this strategy is a preventive treatment in high-risk patients. These improvements may allow an extension of indications of left atrial appendage closure to lower profile risk patients as an alternative to anticoagulant. Indeed, anticoagulant is a risky therapy with hemorrhagic events and observance is a real issue in an asymptomatic population. Finally, there is a lack of data in recent literature comparing left atrial appendage closure to direct oral anticoagulant, widely used in daily practice, as well as cost-effectiveness of this procedure in comparison to anticoagulant.

Modelling projections for the uptake of edoxaban in an European population to 2050: effects on stroke, thromboembolism, and health economics perspectives.

AIMS: In the coming decades, the number of Europeans with atrial fibrillation (AF) is set to rise as the population ages, and so with it will the number of strokes. The risk of thromboembolism (principally stroke and systemic embolism) and death can be reduced by the use of the vitamin K antagonists (VKA, e.g. warfarin) and more so by non-VKA oral anticoagulants (NOACs) such as edoxaban. METHODS AND RESULTS: We modelled the effect of the increasing use of edoxaban in preference to warfarin in a European AF population from both clinical and economic perspectives. We estimate that the introduction of NOACs in 2010 eliminated over 88 000 thromboembolisms and deaths annually, of which over 17 000 were ischaemic strokes. At a 1-year cost of €30k per ischaemic stroke, this strategy saved €510 million annually. Should the use of edoxaban increase from 11% in 2013 to 75% by 2030, we expect that rate of thromboembolism and death will fall from 5.67 to 5.42 total events per million patients per year, which will further eliminate over 12 000 of these events annually. At an inflation-adjusted 1-year cost of approximately €35k per ischaemic stroke, this will save €44.5 million each year. At a conservative rate of increase in the AF population of 2.2-fold from 2005, in 2050 there will be around 180 000 AF-related ischaemic strokes that, at an inflation-adjusted cost of around €62k per stroke, sums to €11 116 million. Should the rate of AF rise 2.6-fold from 2005, then in 2050 there will be 214 500 ischaemic strokes that will cost around €13 300 million. CONCLUSION: Our data point to a substantial increase in the human and economic cost burden of AF and so emphasize the need to reduce this burden. This may be achieved by the increased use of oral anticoagulants, particularly with the NOACs such as edoxaban.

Budget Impact of Increasing Market Share of Patient Self-Testing and Patient Self-Management in Anticoagulation.

BACKGROUND: Patient self-testing (PST) and/or patient self-management (PSM) might provide better coagulation care than monitoring at specialized anticoagulation centers. Yet, it remains an underused strategy in the Netherlands. METHODS: Budget-impact analyses of current and new market-share scenarios of PST and/or PSM compared with monitoring at specialized centers were performed for a national cohort of 260,338 patients requiring long-term anticoagulation testing. A health care payer perspective and 1- to 5-year time horizons were applied. The occurrence of thromboembolic and hemorrhagic complications in the aforementioned patient population was assessed in a Markov model. Dutch-specific costs were applied, next to effectiveness data derived from a meta-analysis on PST and/or PSM. Sensitivity and scenario analyses were performed to assess uncertainty on budget-impact analysis results. RESULTS: Increasing PST and/or PSM usage in the national cohort from the current 15.4% to 50% resulted in savings ranging from €8 million after the first year to €184 million after 5 years. Further increases in the use of PST and/or PSM produced greater savings. Sensitivity analyses revealed budget-impact model sensitivity to the baseline and relative risks of thromboembolic complications. Unfavorable budget impact was found in scenarios exploring an increase in the use of PST alone as well as an increase in the market share of PST and PSM in patients with atrial fibrillation. CONCLUSIONS: Overall study findings indicated that PST and PSM are more favorable alternatives to monitoring at specialized centers in patients without atrial fibrillation.

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

BACKGROUND: The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. OBJECTIVE: To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. METHODS: An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. RESULTS: The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014. CONCLUSIONS: The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.

The clinical effectiveness and cost-effectiveness of point-of-care tests (CoaguChek system, INRatio2 PT/INR monitor and ProTime Microcoagulation system) for the self-monitoring of the coagulation status of people receiving long-term vitamin K antagonist therapy, compared with standard UK practice: systematic review and economic evaluation.

BACKGROUND: Self-monitoring (self-testing and self-management) could be a valid option for oral anticoagulation therapy monitoring in the NHS, but current evidence on its clinical effectiveness or cost-effectiveness is limited. OBJECTIVES: We investigated the clinical effectiveness and cost-effectiveness of point-of-care coagulometers for the self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy, compared with standard clinic monitoring. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index and Cochrane Central Register of Controlled Trials) from 2007 to May 2013. Reports published before 2007 were identified from the existing Cochrane review (major databases searched from inception to 2007). The economic model parameters were derived from the clinical effectiveness review, other relevant reviews, routine sources of cost data and clinical experts' advice. REVIEW METHODS: We assessed randomised controlled trials (RCTs) evaluating self-monitoring in people with atrial fibrillation or heart valve disease requiring long-term anticoagulation therapy. CoaguChek(®) XS and S models (Roche Diagnostics, Basel, Switzerland), INRatio2(®) PT/INR monitor (Alere Inc., San Diego, CA USA), and ProTime Microcoagulation system(®) (International Technidyne Corporation, Nexus Dx, Edison, NJ, USA) coagulometers were compared with standard monitoring. Where possible, we combined data from included trials using standard inverse variance methods. Risk of bias assessment was performed using the Cochrane risk of bias tool. A de novo economic model was developed to assess the cost-effectiveness over a 10-year period. RESULTS: We identified 26 RCTs (published in 45 papers) with a total of 8763 participants. CoaguChek was used in 85% of the trials. Primary analyses were based on data from 21 out of 26 trials. Only four trials were at low risk of bias. Major clinical events: self-monitoring was significantly better than standard monitoring in preventing thromboembolic events [relative risk (RR) 0.58, 95% confidence interval (CI) 0.40 to 0.84; p = 0.004]. In people with artificial heart valves (AHVs), self-monitoring almost halved the risk of thromboembolic events (RR 0.56, 95% CI 0.38 to 0.82; p = 0.003) and all-cause mortality (RR 0.54, 95% CI 0.32 to 0.92; p = 0.02). There was greater reduction in thromboembolic events and all-cause mortality through self-management but not through self-testing. Intermediate outcomes: self-testing, but not self-management, showed a modest but significantly higher percentage of time in therapeutic range, compared with standard care (weighted mean difference 4.44, 95% CI 1.71 to 7.18; p = 0.02). Patient-reported outcomes: improvements in patients' quality of life related to self-monitoring were observed in six out of nine trials. High preference rates were reported for self-monitoring (77% to 98% in four trials). Net health and social care costs over 10 years were £7295 (self-monitoring with INRatio2); £7324 (standard care monitoring); £7333 (self-monitoring with CoaguChek XS) and £8609 (self-monitoring with ProTime). The estimated quality-adjusted life-year (QALY) gain associated with self-monitoring was 0.03. Self-monitoring with INRatio2 or CoaguChek XS was found to have ≈ 80% chance of being cost-effective, compared with standard monitoring at a willingness-to-pay threshold of £20,000 per QALY gained. CONCLUSIONS: Compared with standard monitoring, self-monitoring appears to be safe and effective, especially for people with AHVs. Self-monitoring, and in particular self-management, of anticoagulation status appeared cost-effective when pooled estimates of clinical effectiveness were applied. However, if self-monitoring does not result in significant reductions in thromboembolic events, it is unlikely to be cost-effective, based on a comparison of annual monitoring costs alone. Trials investigating the longer-term outcomes of self-management are needed, as well as direct comparisons of the various point-of-care coagulometers. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013004944. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) causes thromboembolic complications which threaten life and limb. Heparin is administered to virtually every critically ill patient as a protective measure against thromboembolism. Argatroban is a promising alternative anticoagulant agent. However, a safe dose which still provides effective thromboembolic prophylaxis without major bleeding still needs to be identified. METHODS: Critically ill patients (n = 42) diagnosed with HIT at a tertiary medical center intensive care unit from 2005 to 2010 were included in this retrospective analysis. Patient records were perused for preexisting history of HIT, heparin dosage before HIT, argatroban dosage, number of transfusions required, thromboembolic complications and length of ICU stay (ICU LOS). Patients were allocated to Simplified Acute Physiology Scores above and below 30 (SAPS >30, SAPS <30), respectively. For calculations, patients (n = 19) without previous history of HIT were compared to patients (n = 23) with a history of HIT before initiation of argatroban. RESULTS: The mean initial argatroban dosage was below 0.4 mcg/kg/min regardless of SAPS score. Maintenance dosage had to be increased in patients with SAPS <30 to 0.54 ± 0.248 mcg/kg/min (p >0.05) to achieve effective anticoagulation. No thromboembolic complications were encountered. Argatroban had to be discontinued temporarily in 16 patients for a total of 57 times due to diagnostic or surgical procedures, supratherapeutic aPTT and bleeding without increasing the number of transfusions. A history of HIT was associated with a shorter ICU LOS and significantly reduced transfusion need when compared to patients with no history of HIT. Cost calculation favour argatroban due to increased transfusion needs during heparin administration and increase ICU LOS. CONCLUSION: Argatroban can be used at doses < 0.4 mcg/kg/min without an increase in transfusion requirements and at a reduced overall treatment cost compared to heparin.

Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands.

AIM: To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. MATERIALS & METHODS: A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing. RESULTS: Pharmacogenetic dosing increased costs by €33 and quality-adjusted life-years (QALYs) by 0.001. The incremental cost-effectiveness ratios were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol, respectively. At a willingness-to-pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost effective compared with the clinical dosing algorithm. CONCLUSION: Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option.