Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.

Cost-Effectiveness of Left Atrial Appendage Closure for Stroke Reduction in Atrial Fibrillation: Analysis of Pooled, 5-Year, Long-Term Data.

Background Recent publications reached conflicting conclusions about the cost-effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost-effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long-term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin) trials. Methods and Results A Markov model was constructed from a US payer perspective with a lifetime (20-year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5-year data. Warfarin and NOAC inputs were derived from published meta-analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost-effective relative to warfarin by year 7 ($48 674/quality-adjusted life-year) and dominant (more effective and less costly) by year 10. LAAC became cost-effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality-adjusted life-years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost-effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively. Conclusions Using pooled, 5-year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost-effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Cost-Effectiveness of Left Atrial Appendage Closure With the WATCHMAN Device Compared With Warfarin or Non-Vitamin K Antagonist Oral Anticoagulants for Secondary Prevention in Nonvalvular Atrial Fibrillation.

BACKGROUND AND PURPOSE: Once a patient with atrial fibrillation experiences an embolic event, the risk of a recurrent event increases 2.6-fold. New treatments have emerged as viable treatment alternatives to warfarin for stroke risk reduction in secondary prevention populations. This analysis sought to assess the cost-effectiveness of left atrial appendage closure (LAAC) compared with warfarin and the non-vitamin K antagonist oral anticoagulants dabigatran 150 mg, apixaban and rivaroxaban in the prevention of stroke in nonvalvular atrial fibrillation patients with a prior stroke or transient ischemic attack. METHODS: A Markov model was constructed using data from the secondary prevention subgroup analyses of the non-vitamin K antagonist oral anticoagulant and LAAC pivotal trials. Costs were from 2016 US Medicare reimbursement rates and the literature. The cost-effectiveness analysis was conducted from a US Medicare perspective over a lifetime (20 years) horizon. The model was populated with a cohort of 10 000 patients aged 70 years with a CHA2DS2-VASc score of 7 (annual stroke risk=9.60%) and HAS-BLED score of 3 (annual bleeding risk=3.74%). RESULTS: LAAC achieved cost-effectiveness relative to dabigatran at year 5 and warfarin and apixaban at year 6. At 10 years, LAAC had more quality-adjusted life years (4.986 versus 4.769, 4.869, 4.888, and 4.810) and lower costs ($42 616 versus $53 770, $58 774, $55 656, and $58 655) than warfarin, dabigatran, apixaban, and rivaroxaban, respectively, making LAAC the dominant (more effective and less costly) stroke risk reduction strategy. LAAC remained the dominant strategy over the lifetime analysis. CONCLUSIONS: Upfront procedure costs initially make LAAC higher cost than warfarin and the non-vitamin K antagonist oral anticoagulants, but within 10 years, LAAC delivers more quality-adjusted life years and has lower total costs, making LAAC the most cost-effective treatment strategy for secondary prevention of stroke in atrial fibrillation.

Variation in Health Technology Assessment and Reimbursement Processes in Europe.

BACKGROUND: It has been suggested that differences in health technology assessment (HTA) processes among countries, particularly within Europe, have led to inequity in patient access to new medicines. OBJECTIVES: To provide an up-to-date snapshot analysis of the present status of HTA and reimbursement systems in select European countries, and to investigate the implications of these processes, especially with regard to delays in market and patient access. METHODS: HTA and reimbursement processes were assessed through a review of published and gray literature, and through a series of interviews with HTA experts. To quantify the impact of differences among countries, we conducted case studies of 12 products introduced since 2009, including 10 cancer drugs. RESULTS: In addition to the differences in HTA and reimbursement processes among countries, the influence of particular sources of information differs among HTA bodies. The variation in the time from the authorization by the European Medicines Agency to the publication of HTA decisions was considerable, both within and among countries, with a general lack of transparency as to why some assessments take longer than others. In most countries, market access for oncology products can occur outside the HTA process, with sales often preceding HTA decisions. CONCLUSIONS: It is challenging even for those with considerable personal experience in European HTA processes to establish what is really happening in market access for new drugs. We recommend that efforts should be directed toward improving transparency in HTA, which should, in turn, lead to more effective processes.

Cost effectiveness of left atrial appendage closure with the Watchman device for atrial fibrillation patients with absolute contraindications to warfarin.

AIMS: Atrial fibrillation (AF) patients with contraindications to oral anticoagulation have had few options for stroke prevention. Recently, a novel oral anticoagulant, apixaban, and percutaneous left atrial appendage closure (LAAC) have emerged as safe and effective therapies for stroke risk reduction in these patients. This analysis assessed the cost effectiveness of LAAC with the Watchman device relative to apixaban and aspirin therapy in patients with non-valvular AF and contraindications to warfarin therapy. METHODS AND RESULTS: A cost-effectiveness model was constructed using data from three studies on stroke prevention in patients with contraindications: the ASAP study evaluating the Watchman device, the ACTIVE A trial of aspirin and clopidogrel, and the AVERROES trial evaluating apixaban. The cost-effectiveness analysis was conducted from a German healthcare payer perspective over a 20-year time horizon. Left atrial appendage closure yielded more quality-adjusted life years (QALYs) than aspirin and apixaban by 2 and 4 years, respectively. At 5 years, LAAC was cost effective compared with aspirin with an incremental cost-effectiveness ratio (ICER) of €16 971. Left atrial appendage closure was cost effective compared with apixaban at 7 years with an ICER of €9040. Left atrial appendage closure was cost saving and more effective than aspirin and apixaban at 8 years and remained so throughout the 20-year time horizon. CONCLUSIONS: This analysis demonstrates that LAAC with the Watchman device is a cost-effective and cost-saving solution for stroke risk reduction in patients with non-valvular AF who are at risk for stroke but have contraindications to warfarin.

Time to Cost-Effectiveness Following Stroke Reduction Strategies in AF: Warfarin Versus NOACs Versus LAA Closure.

BACKGROUND: Left atrial appendage closure (LAAC) and nonwarfarin oral anticoagulants (NOACs) have emerged as safe and effective alternatives to warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation (AF). OBJECTIVES: This analysis assessed the cost-effectiveness of warfarin, NOACs, and LAAC with the Watchman device (Boston Scientific, Marlborough, Massachusetts) for stroke risk reduction in patients with nonvalvular AF at multiple time points over a lifetime horizon. METHODS: A Markov model was developed to assess the cost-effectiveness of LAAC, NOACs, and warfarin from the perspective of the Centers for Medicare & Medicaid Services over a lifetime (20-year) horizon. Patients were 70 years of age and at moderate risk for stroke and bleeding. Clinical event rates, stroke outcomes, and quality of life information were drawn predominantly from PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) 4-year data and meta-analyses of warfarin and NOACs. Costs for stroke risk reduction therapies, treatment of associated acute events, and long-term care following disabling stroke were presented in 2015 U.S. dollars. RESULTS: Relative to warfarin, LAAC was cost-effective at 7 years ($42,994/quality-adjusted life-years [QALY]), and NOACs were cost-effective at 16 years ($48,446/QALY). LAAC was dominant over NOACs by year 5 and warfarin by year 10. At 10 years, LAAC provided more QALYs than warfarin and NOACs (5.855 vs. 5.601 vs. 5.751, respectively). In sensitivity analyses, LAAC remained cost-effective relative to warfarin ($41,470/QALY at 11 years) and NOACs ($21,964/QALY at 10 years), even if procedure costs were doubled. CONCLUSIONS: Both NOACs and LAAC with the Watchman device were cost-effective relative to warfarin, but LAAC was also found to be cost-effective and to offer better value relative to NOACs. The results of this analysis should be considered when formulating policy and practice guidelines for stroke prevention in AF.

Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension.

OBJECTIVES: The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. BACKGROUND: Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. METHODS: A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. RESULTS: Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was $3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to $31,460 per quality-adjusted life-year. CONCLUSIONS: The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.

Economic implications of the use of basiliximab in addition to triple immunosuppressive therapy in renal allograft recipients: a UK perspective.

OBJECTIVE: To compare resource use and costs in renal transplant recipients treated with basiliximab or placebo plus triple immunosuppressive therapy. DESIGN: International randomised, double-blind, placebo-controlled trial; economic evaluation undertaken alongside the efficacy trial. The economic evaluation was performed from a UK National Health Service hospital perspective. SETTING: 31 centres in 12 countries. PARTICIPANTS: 345 renal transplant recipients were enrolled; 340 were randomised (basiliximab 168; placebo 172) and included in the intention-to-treat analysis. INTERVENTION: Treatment with placebo or basiliximab (20mg intravenous bolus) on day 0 and day 4 after transplantation. MAIN OUTCOME MEASURES: Resource utilisation in multiple categories and treatment costs for basiliximab and placebo-treated patients during the 6-month post-transplantation period. RESULTS: No statistically significant differences were found in any of the economically important categories of resource use or in the mean cost of treatment per person across the whole trial. The mean cost of treatment, including the cost of basiliximab, was pound 16 095 for basiliximab recipients and pound 15 864 (1997/1998 costs) for placebo recipients, a mean difference of pound 231 (95% CI: - pound 1983 to pound 2446), which was not significant. Basiliximab treatment led to a significant reduction in acute rejection episodes (basiliximab 20.8%; placebo 34.9%; p = 0.005). CONCLUSIONS: Basiliximab therapy confers a significant clinical benefit to renal transplant recipients without increasing overall treatment costs.

The economics of basiliximab (Simulect) in preventing acute rejection in renal transplantation.

An economic evaluation was undertaken alongside a multicentre international trial of basiliximab. Resource usage within the trial was assessed, and the cost implications of using basiliximab evaluated. Recipients of a primary cadaveric kidney transplant were recruited into a double-blind trial and received either placebo ( n=186) or basiliximab ( n=190). Clinical outcomes and resource usage were monitored in the 12 months following transplantation. Local unit costs were obtained, and global analysis was undertaken using health sector purchasing-power parity rates. No statistically significant differences were found in the mean cost of treatment per patient. The mean cost of treatment was US$47,940 for basiliximab patients and US$46,280 for placebo patients, a mean difference of US$1,660 (95% confidence interval (CI): -US$4,150, US$7,360; P=0.58). Basiliximab produces clinical benefit in terms of preventing episodes of acute rejection, whilst the difference in the total resource usage and cost of treatment is not statistically significant.