Cardiovascular disease risk assessment using a deep-learning-based retinal biomarker: a comparison with existing risk scores.

Aims: This study aims to evaluate the ability of a deep-learning-based cardiovascular disease (CVD) retinal biomarker, Reti-CVD, to identify individuals with intermediate- and high-risk for CVD. Methods and results: We defined the intermediate- and high-risk groups according to Pooled Cohort Equation (PCE), QRISK3, and modified Framingham Risk Score (FRS). Reti-CVD's prediction was compared to the number of individuals identified as intermediate- and high-risk according to standard CVD risk assessment tools, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the results. In the UK Biobank, among 48 260 participants, 20 643 (42.8%) and 7192 (14.9%) were classified into the intermediate- and high-risk groups according to PCE, and QRISK3, respectively. In the Singapore Epidemiology of Eye Diseases study, among 6810 participants, 3799 (55.8%) were classified as intermediate- and high-risk group according to modified FRS. Reti-CVD identified PCE-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.7%, 87.6%, 86.5%, and 84.0%, respectively. Reti-CVD identified QRISK3-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.6%, 85.5%, 49.9%, and 96.6%, respectively. Reti-CVD identified intermediate- and high-risk groups according to the modified FRS with a sensitivity, specificity, PPV, and NPV of 82.1%, 80.6%, 76.4%, and 85.5%, respectively. Conclusion: The retinal photograph biomarker (Reti-CVD) was able to identify individuals with intermediate and high-risk for CVD, in accordance with existing risk assessment tools.

Real-world data on the incidence, mortality, and cost of ischaemic stroke and major bleeding events among non-valvular atrial fibrillation patients in England.

RATIONALE, AIMS, AND OBJECTIVES: Several novel oral anticoagulants (NOACs) are licensed for atrial fibrillation (AF) treatment in the United Kingdom. We describe the incidence and mortality from ischaemic stroke and major bleeding in non-valvular atrial fibrillation (NVAF) patients in England, including treatment patterns before/following introduction of NOACs, healthcare resource utilization (HRU), and costs post-onset of these events. METHOD: Data were extracted from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics secondary care and Office for National Statistics mortality data. RESULTS: Of 42 966 patients with a first AF record between 2011 and 2016, 9143 patients (21.3%) remained without AF (antiplatelets/antithrombotics) treatment post-index diagnosis. The proportion of patients receiving aspirin for ≥3 months post-index declined during the study (50.6%-5.5%), irrespective of CHA2 DS2 -VASc score, while the proportion prescribed NOACs increased (2.0%-70.1%). Rates of ischaemic stroke per 1000 patient-years (95% CI) were 9.4 (3.8-15.0) with NOACs, 10.4 (8.0-12.9) with warfarin, 20.1 (16.4-23.8) with aspirin, 21.3 (5.3-37.2) with other antiplatelets and 43.6 (39.3-47.8) in patients without AF prescription. Major bleeding occurred at a similar rate with different treatments. All-cause mortality rates were 42.8 (31.4-54.3) with NOACs, 46.3 (41.1-51.5) with warfarin, 56.5 (50.5-62.4) with aspirin, 102.2 (76.2-128.3) with other antiplatelets and 412.8 (399.6-426.0) with no AF prescription. Mean annual National Health Service healthcare costs up to 1 year post-index were lowest in patients receiving aspirin plus other antiplatelets without an event (£6152), and highest in patients with an event without AF prescriptions (£17 957). By extrapolation, national AF HRU in the United Kingdom in 2016 was estimated at £8-16 billion annually. CONCLUSIONS: These data provide temporal insights into AF treatment patterns and outcomes for NVAF patients in England and highlight the need to review higher stroke risk AF patients not receiving antiplatelet/antithrombotic prescriptions.

The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. METHODS: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. RESULTS: Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. CONCLUSION: This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.

AIMS: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients. MATERIALS AND METHODS: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management. RESULTS: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy. LIMITATIONS: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves. CONCLUSIONS: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

Prospective utility study of patients with multiple cardiovascular events.

OBJECTIVES: The effects of acute coronary syndrome (ACS) events on health-related quality-of-life (HRQoL) and the time dependency of these effects are unknown. This study aimed to characterize health utilities in ACS patients to aid development of future economic models estimating the cost per quality-adjusted life-year impact of ACS events and potential treatments. METHODS: Multi-center, non-interventional, longitudinal evaluation of health utility in patients experiencing ACS or stroke events. EuroQol-5 dimension 3 level (EQ-5D-3L) surveys were sent to patients (≥18 years) from three UK centers, 1 month after hospital discharge for myocardial infarction (MI), unstable angina (UA), or stroke. Patient demographics, lifestyle, and baseline utility score were collected in the first survey. Follow-up surveys were sent at 6, 12, 18, and 24 months to prospectively capture utility and subsequent health events. Two methods of patient identification were adopted-prospective, where the patient's qualifying events occurred after the study index date, and retrospective, where the patient's qualifying event occurred prior to the study index date. General healthy population utility values were assumed for pre-event HRQoL. RESULTS: Between January 2011 and March 2014, 2,103 prospectively (n = 1,350)/retrospectively (n = 753) identified patients (mean age = 68.3 years; 67.9% male) responded: MI = 55.9% (n = 1,176), UA = 42.7% (n = 898), stroke = 1.4% (n = 29); 24% had type 2 diabetes. Post-event utility values were lower than general healthy population values, although significant differences in utility between subsequent 6 (n = 1,031, change = -0.002), 12 (n = 1,096, change = -0.008), 18 (n = 1,246, change = -0.007), and 24 (n = 1,277, change = -0.004) month timepoints were not detected. Through multivariate regression analyses, wheelchair use, current smoking, and secondary mental and joint health events were associated with the greatest statistically significant utility decrements. CONCLUSIONS: This study indicates that health utility decreases following a cardiovascular event and, although some improvement occurs over the subsequent 24 months, general healthy population utility is not necessarily attained.

Patient perspective on the management of atrial fibrillation in five European countries.

BACKGROUND: Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS: Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. RESULTS: Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions.

Predictors, cost, and outcomes of patients with acute coronary syndrome who receive optimal secondary prevention therapy: results from the antiplatelet treatment observational registries (APTOR).

BACKGROUND: We sought to evaluate outcomes, costs of care, quality of life and predictors at 12 months in patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and evaluated use of optimal secondary prevention therapy, defined as use of aspirin and clopidogrel along with ≥ 3 of the following 4 therapies at both hospital discharge and at one-year post-PCI: statins, beta-blockers, ARB/ACE-inhibitors, and exercise or diet. METHODS: Data were from the prospective, observational APTOR study of 14 European countries from 2007 to 2009 (n=4184 patients). RESULTS: Optimal therapy was received in 43% of patients. Use of optimal therapy varied significantly by country. Diet or exercise at 1 year was more likely prescribed to the optimal cohort (34% vs 16%) as was dual antiplatelet therapy (99% vs 49%). Rates of CV event (3.1% vs 3.5%), bleeding (2.9% vs 2.8%) and mortality (0.9% vs 1.3%) at 1 year were similar between the optimal and non-optimal cohorts, respectively. Total costs were similar for both cohorts, but differences in post-discharge costs were observed (optimal: £1760 [£1682-£1844]; non-optimal: £1492 [£1434-£1554]), primarily due to post-discharge medication and resource use. CONCLUSIONS: In conclusion, in this contemporary, European ACS-PCI registry, optimal therapy was low (<50%) overall, particularly for diet or exercise and dual antiplatelet therapy, highlighting a considerable gap between evidence-based guidelines and implementation of such treatments. Whether this gap reflects a missed opportunity to improve patient outcomes or whether it reflects appropriate deviation from guidelines by front-line clinicians requires further investigation.

Telemonitoring after discharge from hospital with heart failure: cost-effectiveness modelling of alternative service designs.

OBJECTIVES: To estimate the cost-effectiveness of remote monitoring strategies versus usual care for adults recently discharged after a heart failure (HF) exacerbation. DESIGN: Decision analysis modelling of cost-effectiveness using secondary data sources. SETTING: Acute hospitals in the UK. PATIENTS: Patients recently discharged (within 28 days) after a HF exacerbation. INTERVENTIONS: Structured telephone support (STS) via human to machine (STS HM) interface, (2) STS via human to human (STS HH) contact and (3) home telemonitoring (TM), compared with (4) usual care. MAIN OUTCOME MEASURES: The incremental cost per quality-adjusted life year (QALY) gained by each strategy compared to the next most effective alternative and the probability of each strategy being cost-effective at varying willingness to pay per QALY gained. RESULTS: TM was the most cost-effective strategy in the scenario using these base case costs. Compared with usual care, TM had an estimated incremental cost effectiveness ratio (ICER) of £11 873/QALY, whereas STS HH had an ICER of £228 035/QALY against TM. STS HM was dominated by usual care. Threshold analysis suggested that the monthly cost of TM has to be higher than £390 to have an ICER greater than £20 000/QALY against STS HH. Scenario analyses performed using higher costs of usual care, higher costs of STS HH and lower costs of TM do not substantially change the conclusions. CONCLUSIONS: Cost-effectiveness analyses suggest that TM was an optimal strategy in most scenarios, but there is considerable uncertainty in relation to clear descriptions of the interventions and robust estimation of costs.

Treatment, outcomes, costs, and quality of life of women and men with acute coronary syndromes who have undergone percutaneous coronary intervention: results from the antiplatelet therapy observational registry.

BACKGROUND: Treatment, outcomes, costs, and quality of life after percutaneous coronary intervention (PCI) were compared between women and men with acute coronary syndromes (ACS) using data from the Antiplatelet Therapy Observational Registry (APTOR). METHODS: Fourteen European countries participated in this noninterventional, prospective, observational cohort registry, which enrolled patients with ACS who underwent PCI from 2007 to 2009. The 12-month outcomes included bleeding, cardiovascular events, and mortality. Quality of life was measured using the EQ-5D™ (EuroQol Group) health index and the visual analog scale. RESULTS: The APTOR registry included 4546 patients, of whom 1047 (23%) were women and 3499 (77%) were men. The women were older (mean age, 67 vs 61 years) and had higher rates of diabetes mellitus and hypertension. A greater proportion of the men were smokers (40% vs 30%). Approximately 70% of the patients underwent PCI on the day of the qualifying ACS event. Women and men received similar medications at the time of PCI, hospital discharge, and 12-month follow-up visit. Bleeding, cardiovascular events, and mortality occurred at higher rates in women than in men, but the differences were not statistically significant. At 12 months post-PCI, women reported lower quality-of-life scores on the EQ-5D™ health index and the visual analog scale than did men. The mean total cost of care was £6252 (€7189) for women and £5841 (€6717) for men; the differences may be driven by resource use after discharge from the hospital. CONCLUSION: Women with ACS tended to be older and had more comorbidities than men, but both sexes experienced similar outcomes after 1 year. This study indicated no differences in treatment between sexes.

Prasugrel vs clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a model-based cost-effectiveness analysis for Germany, Sweden, the Netherlands, and Turkey.

OBJECTIVE: To evaluate the long-term cost-effectiveness of 12-months treatment with prasugrel vs clopidogrel from four European healthcare systems' perspectives (Germany, Sweden, the Netherlands, and Turkey). METHODS: In the TRITON-TIMI 38 trial, patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) were treated with prasugrel or clopidogrel. Prasugrel reduced the composite end-point (cardiovascular death, MI, or stroke), but increased TIMI major bleeding. A Markov model was constructed to facilitate a lifetime horizon for the analysis. A series of risk equations constructed using individual patient data from TRITON-TIMI 38 was used to estimate risks of clinical events. Quality-adjusted life-years (QALYs) were derived by weighting survival time by estimates of health-related quality-of-life. Incremental cost-effectiveness is presented based on differences in treatments' mean costs and QALYs for the licensed population in TRITON-TIMI 38, and the sub-groups of UA-NSTEMI, STEMI, diabetes, and the 'core clinical cohort' (<75 years, ≥60 kg, no history of stroke or TIA). RESULTS: Mean cost of study drug was €364 (Turkey) to €818 (Germany) higher for prasugrel vs clopidogrel. Rehospitalization costs at 12 months were lower for prasugrel due to reduced rates of revascularization, although hospitalization costs beyond 12 months were higher due to longer life expectancy associated with lower rates of non-fatal MI in the prasugrel group. The incremental cost per QALY saved with prasugrel in the licensed population ranged from €6520 (for Sweden) to €14,350 for (Germany). Prasugrel's cost per QALY was more favourable still in the STEMI and diabetes sub-groups of the licensed population. LIMITATIONS: Probabilistic analyses of the whole trial population is impractical due to the number of individual patient profiles over which population level results are calculated. CONCLUSION: Among patients undergoing PCI for ACS, treatment with prasugrel compared with clopidogrel resulted in favourable cost-effectiveness profiles from these healthcare systems' perspectives.

Cost-effectiveness of aldosterone antagonists for the treatment of post-myocardial infarction heart failure.

OBJECTIVE: To assess the cost-effectiveness of eplerenone versus spironolactone as an adjunctive therapy to standard care in patients with heart failure (HF) following a myocardial infarction (post-MI) from the perspective of the National Health Service in the United Kingdom. METHODS: A systematic review was conducted, and a Bayesian meta-regression approach was used to establish the relative effectiveness of eplerenone and spironolactone by using evidence from randomized controlled trials. A decision analytic model was developed to assess the costs and consequences associated with the primary outcome of the trials over a lifetime time horizon. RESULTS: The incremental cost-effectiveness ratio of eplerenone compared with that of standard care alone was £ 4457 and £ 7893 for each additional quality-adjusted life-year when 2-year and lifetime treatment duration was assumed, respectively. In both scenarios, spironolactone did not appear cost-effective compared with eplerenone. The results were sensitive to the higher relative effectiveness estimated for eplerenone compared with spironolactone from the meta-regression. When a class effect was assumed for the effect on mortality and hospitalizations, spironolactone emerged as the most cost-effective treatment. CONCLUSIONS: Eplerenone appears more cost-effective than spironolactone for the treatment of post-MI HF. These findings, however, remain subject to important uncertainties regarding the effects of treatment on major clinical events. An adequately powered, well-conducted randomized controlled trial that directly compares spironolactone and eplerenone may be required to provide more robust evidence on the optimal management of post-MI HF. Despite these uncertainties, the use of an aldosterone antagonist was consistently demonstrated to be a highly cost-effective strategy for the management of post-MI HF in the National Health Service.

Clinical outcomes, resource use, and costs at 1 year in patients with acute coronary syndrome undergoing PCI: results from the multinational APTOR registry.

BACKGROUND: Limited prospectively collected data are available on the total outcomes, cost estimates, and quality of life associated with treatment of acute coronary syndrome (ACS) through 1 year in a nonclinical-trial setting, or on the impact of new clinical events by 1 year on resource utilization and costs. METHODS: The Antiplatelet Therapy Observational Registry (APTOR) 12-month study followed 1,335 concurrently recruited ACS patients undergoing percutaneous coronary intervention (PCI) and treated with antiplatelet therapy from France, Spain, and the United Kingdom in a "real world" clinical setting. Data were collected on clinical events, resource utilization, quality of life, and cost estimates through 1-year follow-up. RESULTS: By 1 year, 14.4% (95% CI 12.7-16.4%) of patients experienced a clinical event of death, MI, stroke, unstable angina, urgent target vessel revascularization, or acute heart failure. Costs by 1 year were higher among those who had a new clinical event (£8,988, 95% CI £7,848, £10,395) as compared with those with no events (£5,809, 95% CI £5,486, £6,161). This increased cost was due to higher postdischarge resource use costs. Using the EQ-5D assessment at 1 year, quality of life was directionally lower in those patients who had experienced a new clinical event. CONCLUSIONS: The risk of experiencing a new clinical event during the year following an ACS, which was treated with PCI, remains high among European patients, with one-seventh of patients having a new event. These additional clinical outcomes reduce quality of life and increase health care expenditures, expanding the already high cost of treatment for ACS.

A cost-utility analysis of clopidogrel in patients with ST elevation acute coronary syndromes in the UK.

OBJECTIVE: To assess the long-term cost effectiveness of treatment for 1 month, and for 1 year with clopidogrel in addition to standard therapy (including aspirin) compared with standard therapy alone, in patients diagnosed with ST elevation acute myocardial infarction (STEMI) in the UK. DESIGN: Cost utility analysis using a cohort Markov model, incorporating clinical data from two pivotal clinical trials (the COMMIT/CCS-2 and CLARITY-TIMI 28 trials) and data from UK and non-UK observational studies. SETTING: Health economic evaluation carried out from the perspective of the UK NHS. PATIENTS: A representative cohort of 1000 UK patients aged 60 years, diagnosed with STEMI. INTERVENTIONS: 75 mg/day clopidogrel, with and without a 300 mg loading dose, in addition to standard therapy (including aspirin, 75-325 mg/day) for 1 month, and for 1 year, followed by standard therapy alone for their remaining lifetime, or standard therapy alone (including aspirin, 75-325 mg/day) for their remaining lifetime. MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life-year (QALY) gained (ICER). RESULTS: For the 1-month treatment option both the COMMIT/CCS-2 and CLARITY-TIMI 28 trials have ICERs below 2500 pounds. For the 1-year treatment option both trials have ICERs below 4000 pounds. Extensive univariate and probabilistic sensitivity analyses showed these results to be robust. CONCLUSIONS: In combination with previous economic analyses of clopidogrel in NSTEMI patients, this paper demonstrates that clopidogrel appears to offer a cost-effective treatment option for all ACS patients.

Age >or=75 years is associated with greater resource utilization following coronary artery bypass grafting.

We examined whether complication rates and resource utilization among elderly patients undergoing coronary artery bypass grafting (CABG) differed from their younger counterparts. A retrospective review of prospectively collected data was conducted of 2936 patients undergoing first-time isolated CABG. Demographic and baseline clinical characteristics were collected, and patients grouped according to age into those <75 years (n=2424, younger) and >or=75 years (n=512, older). Major postoperative complications were recorded and data collected on indicators of resource utilization, which included intensive care unit (ICU) length of stay (LOS), postoperative LOS and total hospital LOS. In comparison with younger patients, older patients were more likely to be female (26.6% vs. 18.1%, P<0.0001) and require an urgent procedure (46.4% vs. 33.3%, P<0.0001). Postoperative complications were significantly higher in elderly patients (43.7% vs. 23.0%; odds ratio (OR)=2.5, 95% confidence interval (CI) [2.0-3.1]; P<0.0001). Older patients incurred longer intensive care stays (2 days interquartile range (IQR) [1-3] vs. 1 day IQR [1-2]; P<0.0001) and a longer postoperative stay (8 days IQR [6-11] vs. 6 days IQR [5-8]; P<0.0001). Multivariate logistic regression analysis showed age >or=75 years was an independent predictor of postoperative LOS (OR=1.23, 95% CI [0.49-1.96]; P=0.001). Older patients aged >or=75 years undergoing CABG had significantly higher rates of postoperative complications and greater resource utilization than their younger counterparts.

Adherence to guidelines for sensitivity analysis: cost-effectiveness analyses of dual oral antiplatelet therapy.

OBJECTIVE: Cost-effectiveness analyses of new treatments for cardiovascular disease frequently require input parameters whose values are known with uncertainty due to limited data. The objective of this paper is to examine the extent to which published sensitivity analyses addressing this uncertainty adhere to Health Technology Assessment (HTA) guidelines. RESEARCH DESIGN AND METHODS: A systematic review of published cost-effectiveness analyses was performed for an example drug treatment scenario, dual oral antiplatelet therapy compared with aspirin alone following acute coronary syndromes and/or percutaneous coronary intervention. The following medical literature databases were searched for articles published from January 1997 to June 2007: PubMed, Cochrane Collaboration, EMBASE and the Health Economic Evaluation Database (HEED). Evidence tables were created to show the sensitivity of the cost-effectiveness estimates to changes in the input parameter values, as well as the data sources used for the reference-case and sensitivity analysis input parameter values. The extent to which the sensitivity analyses adhered to HTA guidelines were also examined. RESULTS: Cost-effectiveness ratios were most sensitive to changes in the efficacy of dual antiplatelet therapy and reference-case model assumptions about costs beyond the trial period. Although alternative values tested in the sensitivity analysis for some input parameters were based on observed ranges or distributions, alternative values tested for many other input parameters were assumed without justification. CONCLUSIONS: Sensitivity analyses in the cost-effectiveness studies of dual oral antiplatelet therapy were not fully adherent with HTA guidelines. In particular, long-term costs and benefits were not always included in the sensitivity estimates, the impact of differential effects on death and myocardial infarction was not explored, and justification for the alternative parameter values tested was not always provided.

Fondaparinux versus Enoxaparin in non-ST-elevation acute coronary syndromes: short-term cost and long-term cost-effectiveness using data from the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators (OASIS-5) trial.

BACKGROUND: The study aimed to compare the short-term costs and long-term cost-effectiveness of 2 antithrombotics, fondaparinux and enoxaparin, for non-ST-elevation acute coronary syndrome in the United States. METHODS: It was based on a large randomized trial of 20,078 patients Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators [OASIS-5] comparing the therapies in these patients. In OASIS-5, fondaparinux patients had about half the rate of major bleeding 9 days after randomization and at least as good clinical outcomes (death, myocardial infarction, major bleeding and stroke) after 6 months of follow-up. Health care resource use and clinical efficacy data from the trial were incorporated into a cost-effectiveness model as applied to a general US health care system both for the time horizon of the study (6 months) and over the longer term. RESULTS: The 180-day cost analysis indicates that fondaparinux would generate a cost saving of $547 per patient (95% CI $207-$924). Sensitivity analysis suggested that savings could vary between $494 and $733. When 180-day cost and clinical results were extrapolated to long-term cost-effectiveness, fondaparinux was dominant (less costly and more effective in terms of quality-adjusted life-years) under most scenarios. CONCLUSIONS: Fondaparinux is a more cost-effective antithrombotic agent than enoxaparin in non-ST-elevation acute coronary syndrome. This is true across the range of event risks seen in OASIS-5.

Cost effectiveness of paclitaxel-eluting stents for patients undergoing percutaneous coronary revascularization: results from the TAXUS-IV Trial.

OBJECTIVES: This study sought to compare aggregate medical care costs for patients undergoing percutaneous coronary intervention with paclitaxel-eluting stents (PES) and bare-metal stents (BMS) and to formally evaluate the incremental cost effectiveness of PES for patients undergoing single-vessel percutaneous coronary intervention. BACKGROUND: Although the cost effectiveness of SES has been studied in both clinical trials and decision-analytic models, few data exist on the cost effectiveness of alternative drug-eluting stent (DES) designs. In addition, no clinical trials have specifically examined the cost effectiveness of DES among patients managed without mandatory angiographic follow-up. METHODS: We performed a prospective economic evaluation among 1,314 patients undergoing percutaneous coronary revascularization randomized to either PES (N = 662) or BMS (N = 652) in the TAXUS-IV trial. Clinical outcomes, resource use, and costs (from a societal perspective) were assessed prospectively for all patients over a 1-year follow-up period. Cost effectiveness was defined as the incremental cost per target vessel revascularization (TVR) event avoided and was analyzed separately among cohorts assigned to mandatory angiographic follow-up (n = 732) or clinical follow-up alone (n = 582). RESULTS: The PES reduced TVR by 12.2 events per 100 patients treated, resulting in a 1-year cost difference of 572 dollars per patient with incremental cost-effectiveness ratios of 4,678 dollars per TVR avoided and 47,798 dollars/quality-adjusted life year (QALY) gained. Among patients assigned to clinical follow-up alone, the net 1-year cost difference was 97 dollars per patient with cost-effectiveness ratios of 760 dollars per TVR event avoided and $5,105/QALY gained. CONCLUSIONS: In the TAXUS-IV trial, treatment with PES led to substantial reductions in the need for repeat revascularization while increasing 1-year costs only modestly. The cost-effectiveness ratio for PES in the study population compares reasonably with that for other treatments that reduce coronary restenosis, including alternative drug-eluting stent platforms.