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Healthcare delivery, economics and global health


Health economic analysis of ticagrelor in patients
with acute coronary syndromes intended for
non-invasive therapy
M Janzon,1,2 S James,3 C P Cannon,4 R F Storey,5 C Mellström,6 J C Nicolau,7
L Wallentin,3 M Henriksson2,8

▸ Additional material is ABSTRACT non-ST-elevation ACS,3 4 but whether this consist-
published online only. To view Objective To investigate the cost effectiveness of ently reduces mortality remains unclear.
please visit the journal online
ticagrelor versus clopidogrel in patients with acute Dual antiplatelet therapy with aspirin and a
heartjnl-2014-305864). coronary syndromes (ACS) in the Platelet Inhibition and P2Y12 inhibitor is recommended for 12 months in
Patient Outcomes (PLATO) study who were scheduled for patients with ACS not undergoing invasive
For numbered affiliations see
end of article. non-invasive management. therapy.3 In the Platelet Inhibition and Patient
Methods A previously developed cost effectiveness Outcomes (PLATO) trial in 18 624 patients with
Correspondence to model was used to estimate long-term costs and ACS,5 a prespecified analysis of 5216 patients who
Dr Magnus Janzon, outcomes for patients scheduled for non-invasive were planned at randomisation for non-invasive
Department of Cardiology,
University Hospital, Linköping management. Healthcare costs, event rates and health- management demonstrated that, compared with
SE-581 85, Sweden; related quality of life under treatment with either clopidogrel, ticagrelor significantly reduced the rate ticagrelor or clopidogrel over 12 months were estimated of ischaemic events including the primary compos-
from the PLATO study. Long-term costs and health ite end point of myocardial infarction, stroke or
Received 14 March 2014
outcomes were estimated based on data from PLATO death from vascular causes.6 Cardiovascular and
Revised 8 August 2014
Accepted 21 August 2014 and published literature sources. To investigate the all-cause mortality were also significantly reduced
Published Online First importance of different healthcare cost structures and life with ticagrelor.6 The incidence of total major
16 September 2014 expectancy for the results, the analysis was carried out bleeding and non-coronary artery bypass grafting-
from the perspectives of the Swedish, UK, German and related major bleeding was numerically higher with
Brazilian public healthcare systems. ticagrelor than with clopidogrel,6 but these failed
Results Ticagrelor was associated with lifetime quality- to reach statistical significance. These findings were
adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 consistent with the overall PLATO results.
in the UK, 0.17 in Germany and 0.13 in Brazil compared In addition to clinical benefit, healthcare decision
with generic clopidogrel, with increased healthcare costs makers need to consider costs in order to prioritise
of €467, €551, €739 and €574, respectively. The cost treatments. The cost effectiveness of ticagrelor over
per QALY gained with ticagrelor was €2747, €3395, generic clopidogrel in the overall PLATO popula-
€4419 and €4471 from a Swedish, UK, German and tion has been shown from an European healthcare
Brazilian public healthcare system perspective, perspective.7 The economic implications of using
respectively. Probabilistic sensitivity analyses indicated ticagrelor in the subgroup of patients with ACS
that the cost per QALY gained with ticagrelor was below intended for non-invasive management were not
conventional threshold values of cost effectiveness with analysed in the previous study and the aim of this
a high probability. work was therefore to investigate the cost effective-
Conclusions Treatment of patients with ACS scheduled ness of ticagrelor with generic clopidogrel in this
for 12 months’ non-invasive management with ticagrelor subgroup. In order to investigate the impact of tica-
is associated with a cost per QALY gained below grelor in a range of countries with different health-
conventional threshold values of cost effectiveness care systems and life expectancy, the cost
compared with generic clopidogrel. effectiveness analysis was conducted from the per-
Trial registration number NCT000391872. spectives of four different public systems: Sweden,
the UK, Germany and Brazil.
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INTRODUCTION The PLATO trial (NCT00391872) enrolled 18 624
Worldwide, 40–60% of patients with non-ST- patients from 43 countries between October 2006
elevation acute coronary syndromes (ACS) are med- and July 2008; full details of the study design,
ically managed without revascularisation. These inclusion criteria and results have already been pub-
patients have an increased risk of mortality, and lished.5 6 Briefly, patients with ST-segment eleva-
receive antiplatelet therapy after discharge less fre- tion ACS scheduled for primary percutaneous
To cite: Janzon M, James S, quently than patients who undergo revascularisa- coronary intervention or non-ST segment elevation
Cannon CP, et al. Heart tion.1 2 Current guidelines recommend an early ACS, with onset of symptoms during the previous
2015;101:119–125. invasive approach in high-risk patients with 24 h, were enrolled.

Janzon M, et al. Heart 2015;101:119–125. doi:10.1136/heartjnl-2014-305864 119

UK. At the time of randomisation.7 Brazilian. et al. supplementary table S1). model and its application have been published previously. UK and was applied to derive QALY-weights from the answers of the Brazilian analyses.6 Of these.8 9 Costs pathways were based on EuroQol 5 dimensions (EQ-5D)16 data and health outcomes were discounted according to guidelines: collected prospectively in PLATO. of non-invasive patients whereas the overall treatment effects ued for 6–12 months. when analysing resource use. Expert opinion was used for those German were used to determine rates of cardiovascular events. Resource use. ACS. use data collected in PLATO. acute coronary syndrome. a Markov structure was used for long-term supplied in an online appendix to this article (see online extrapolation in order to estimate quality-adjusted survival con.7 and is used with the permission of the European Heart Journal. the cost-effectiveness analysis was conducted from were alive. following clinical pathways: non-fatal MI occurring before a tion. doi:10.7 A 12-month QALY estimate was calculated incremental cost effectiveness ratios showing the additional cost for every patient with planned 12-month follow-up: for all per unit of health outcome of treating patients with ticagrelor patients still alive after all three measurements (index.54. et al. This is a conservative assumption as it disfavours the the perspectives of four different public systems: those of ticagrelor strategy and follows Nikolic et al. randomised treatment contin. (4) Mortality risk at the 1st year after a non-fatal MI. Full details of the model are provided in table 1. (2) Risk of non-fatal stroke for patients with no MI or stroke in the PLATO study. Patients were randomised to receive either fatal stroke occurring before any potential non-fatal MI with no ticagrelor 90 mg twice daily after a loading dose of 180 mg. (5) Mortality risk at the 1st year after a non-fatal stroke. economics and global health At randomisation. or subsequent fatal event. Heart 2015. The widely used UK tariff 3%. physicians initially allocated patients to Data intended invasive or conservative non-invasive management via The event risks for 12 months treatment with ticagrelor and clo- an interactive voice randomisation system. the UK.101:119–125. as previously described. Following the approach in Nikolic 300 mg load allowed for patients undergoing percutaneous cor.86 and €1=R$2. the area under the curve was estimated Figure 1 Decision tree and Markov model. 3. 6 months compared with clopidogrel. To handle administrative censoring applied. These initial deci. 1516 clopidogrel). (7) Mortality risk at second and subsequent years after a non-fatal stroke.33). use and health-related quality of life for 12 months of therapy. €1=£0.7 Individual patient data from PLATO patient in the study. German and Swedish unit costs were derived from national Lifetime costs and outcomes were estimated using the same public databases for each country.7 and in line with the clinical findings in PLATO. only patients eligible for Cost estimates per clinical pathway were based on resource 12 months’ follow-up were included in the 12-month cost ana. no further event. PLATO. 5216 observed in the full PLATO sample were applied to derive the (28%) patients were allocated initially to non-invasive manage. German. 2601 and 2615 were randomised to ticagrelor the treatment effect observed in the non-invasive cohort was and clopidogrel. (3) Mortality risk for patients with no MI or stroke in the PLATO study.10 11 Results are presented as EQ-5D instrument. in Euros (€) using 2010 prices and the average exchange rates Quality-adjusted life-year (QALY) estimates for the clinical for that year (€1=Kr9. This model structure was developed by Nikolic et al.1136/heartjnl-2014-305864 .12–15 and were multiplied with two-part decision-analytical model used in the previous PLATO observed resource use to arrive at a total healthcare cost per cost effectiveness analysis. (6) Mortality risk at second and subsequent years after a non-fatal MI.7 The drug cost for Sweden. a non- clinical judgement. respectively. 120 Janzon M. pidogrel were estimated for different clinical pathways using a sions were non-binding but were required to create statistically parametric survival model and are reported in table 1 for the valid prospectively identified therapy groups. and 12 months). Platelet Inhibition and Patient Outcomes.7 Markov model transitions shown in this figure: (1) risk of non-fatal myocardial infarction (MI) for patients with no MI or stroke in the PLATO study. Germany and Brazil. death occurring at any point in the study clopidogrel 300 mg loading dose (if required) with an additional follow-up. unit cost data and within-trial cost estimates are Beyond the 1st year.7 To Daily drug costs for ticagrelor and generic clopidogrel were investigate the impact of different healthcare systems and life applied during the 12 months of therapy as long as patients expectancy. lysis (1499 ticagrelor. followed by 75 mg daily. The estimated costs per clinical ditional on whether a non-fatal stroke or a non-fatal myocardial pathway derived from the cost analysis and applied in the infarction (MI) had occurred (figure 1).6 the risks onary intervention (PCI) . physicians were free to manage patients according to their potential non-fatal stroke with no subsequent fatal event. Healthcare delivery. risks for ticagrelor-treated patients. after randomisa. All costs were expressed each country is reported in table 1. resource unit costs that were not feasible to derive from another source.5% and 5% per annum in the Swedish. In an alternative scenario ment. respectively. All patients for clopidogrel-treated patients were estimated using the sample also received aspirin if tolerated.

1034 with ticagrelor was associated with increased healthcare costs of QALY decrement post-stroke state 0.00 grammed and analysed in Microsoft Excel (Microsoft Risk of death in the post-MI state* 3. quality-adjusted life-year.16. respectively. USA: Risk of death in the no event state* 2.0755 and Germany resulted in a smaller QALY gain for ticagrelor in QALY decrement post-MI state 0.7388 0. Furthermore.7418 0. Brazil. USA).8704 0.17. 243) clopidogrel (table 3).0642 0. Germany and Brazil. Long-term during the first 10 days.21 0.0119 0.7 (Stata Annual risk of stroke in the no event state 0. 719. 413) UK. Annual risks of non-fatal MI alternative scenario included only patients with NSTE-ACS who and non-fatal stroke (transitions 1 and 2 in figure 1) were esti. 4336. Texas. Redmond. Uncertainty in the estimated incremental cost effectiveness tion of HRs to account for increase in risk due to further events ratios due to sampling uncertainty in the estimated input param- (transitions 3–7 in figure 1). Janzon M.2445 0. QALY.0811 0.7418 QALY death clinical pathway 0. The cost per QALY gained with ticagrelor †Values for the UK. 14 925. was €2747. †2012 prices.8130 the 12 months on therapy. doi:10. UK.101:119–125.2445 QALY no MI or stroke clinical pathway 0. economics and global health Table 1 Event risks.2414 0.1136/heartjnl-2014-305864 121 .91 0. 3421.17 and 0.0110 0.7667 0.27 0.13 in Sweden. et al.0642 0.8737 the lower rate of mortality seen with ticagrelor treatment during QALY weight in the non-fatal state age 70–79 years 0.0119 0. for patients who died. study drug costs are entered as separate parameters.0619 0. Washington. non-invasive management.7667 0.8422 0.8460 0.0619 0. QALY. myocardial infarction.8704 0. did not undergo any revascularisation procedure (PCI or coron- mated by extrapolating observed hazard functions from the clo. €739 and €563 in Sweden.7418 0. compared with generic Cost in the no-event state (€)† 1376 (253.1034 €467. 792) In the base-case analysis of patients with ACS scheduled for Cost in the non-fatal stroke state (€)† 12 977 (15 262. Risk of death in the non-fatal stroke state* 7.7667 0. The QALY gains were primarily driven by QALY weight in the non-fatal state age<69 years 0.0110 0. costs and quality of life during 12 months of therapy Sweden UK Germany Brazil Parameter Ticagrelor Clopidogrel Ticagrelor Clopidogrel Ticagrelor Clopidogrel Ticagrelor Clopidogrel Probability non-fatal MI clinical pathway 0. Shorter life expectancy and a higher QALY weight in the non-fatal state age >79 years 0.8422 0.52 QALY non-fatal MI clinical pathway 0.06 2.7697 QALY non-fatal stroke clinical pathway 0. Annual risk of MI in the no event state 0. treatment QALY decrement non-fatal stroke state 0. incremental cost Table 2 Parameters for long-term extrapolation effectiveness.0119 0.7388 0.17 survival was based on country-specific life tables with applica. An 12 months) are listed in table 2. The base-case analysis was based on the full population of Parameters used for long-term extrapolation (beyond patients with ACS scheduled non-invasive management.8422 0.8704 0. Healthcare delivery.7697 0. 2971) Base-case analysis Cost in the post-MI state (€)† 4172 (332. Germany and *HR versus standard mortality.7537 discount rate of future benefits in Brazil versus Sweden.0535 0. €3395.8452 0.0110 Probability death clinical pathway 0. the Cost in the poststroke state (€)† 3506 (4237.0755 the Brazilian analysis.0535 0. myocardial infarction.7697 0. assuming a linear relationship between all time points.34 0.2445 0.7388 0.0535 0.35 2. The estimated mean per patient 12-month QALY estimates per clinical pathway are reported in Analysis table 1.0619 Probability non-fatal stroke clinical pathway 0.0110 0. MI.2445 0. ary artery bypass grafting (CABG)) with or without angiography pidogrel arm in PLATO beyond 1 year’s follow-up. MI.8452 0. The last each health state in the Markov model were based on PLATO available estimates were carried forward until the date of death data and published literature (see Nikolic et al7).7418 0.07 2.0. the UK QALY decrement non-fatal MI state 0. German and Brazilian perspectives.0535 0.8460 Healthcare cost of non-fatal MI clinical pathway (€)* 23 653 23 994 18 365 18 606 14 777 14 964 4401 4482 Healthcare cost of non-fatal stroke clinical pathway (€)* 22 925 23 266 16 731 16 972 13 193 13 380 2865 2946 Healthcare cost of death clinical pathway (€)* 17 227 17 568 12 267 12 508 9 921 10 108 2496 2577 Healthcare cost of no MI or stroke clinical pathway (€)* 10 294 10 635 8193 8434 6681 6856 1998 2079 Daily cost of study drug (€)† 2.8704 0.0811 0.2414 0. College Station.7667 0.0642 0.003 Statistical Software: Release 7.7388 0.00 Corporation.8452 *Healthcare costs excluding drug costs. respectively.8460 0. 0. €4419 and €4471 from Swedish.8460 0. Compared with clopidogrel.0119 0.2414 0.00 Stata Corporation). The decision-analytical model was pro- Risk of death in the non-fatal MI state* 6. Heart 2015.0811 0.00 RESULTS Cost in the non-fatal MI state (€)† 15 656 (5836. 0. respectively (table 3).0811 Probability no MI or stroke clinical pathway 0.2414 0. 9558. €545.019 All statistical analyses were performed using Stata V.0642 0.7697 0. Germany and Brazil shown in parentheses.43 Risk of death in the poststroke state* 3. quality-adjusted life-year.8452 0. scenarios were also explored to Parameter Mean value investigate uncertainty related to model assumptions and data inputs not associated with sampling uncertainty. while costs and QALY weights for eter values was evaluated by employing probabilistic sensitivity analysis in which simulation was used to propagate uncertainty in individual model inputs through the model in order to assess the uncertainty in the outcome of interest. the UK.0619 0. ticagrelor was associated with life- 1527) time QALY gains of 0.8422 0.

1136/heartjnl-2014-305864 . Germany and Brazil. spectives. German (figure 4B) and from Swedish. The results in bold are based on the probabilistic simulation which does not provide meaningful levels of significant of this ratio statistic. €3483 (incre- The cost effectiveness acceptability curves show the probabil. yielded a cost effective- the UK. applying the treatment effect ability that the incremental cost effectiveness ratio of ticagrelor observed in the non-invasive patients rather than the overall is below conventional willingness-to-pay thresholds in Sweden. Given previously reported results of cost effectiveness the cost effectiveness results when analysing men and women of ticagrelor this finding is not particularly surprising as we Figure 2 (A) Cost effectiveness plane and (B) cost effectiveness acceptability curve.1258) Swedish (figure 2B). Heart 2015. tal costs €503 and incremental QALY 0. separately. 122 Janzon M.93 0. €4503 ity of ticagrelor being cost effective compared with generic clo.1692) and pidogrel at different threshold values of cost effectiveness in the €4489 (incremental costs €565 and incremental QALY 0. See for example the original publication. respectively. and at different ages. mental costs €566 and incremental QALY 0. The majority of simulations are in the north-east non-ST-elevation ACS who had no revascularisation during the quadrant for all four countries.10 8. Findings appeared robust in the lor of €5252 and €5917 from German and Brazilian healthcare alternative scenarios and the probabilistic sensitivity analyses systems. 4A and 5A) show the uncertainty around the cost effective.64 0. ciated with a QALY gain and an incremental cost compared The cost per QALY gained with ticagrelor was €2920 (incremen- with generic clopidogrel. respectively.1625). treatment effect from the PLATO study.77 6. Finally. QALY. the UK. first 10 days17 shows similar results to the base-case analysis. The results of the probabilistic sensitivity analyses (figures 2A. Healthcare delivery.17 €2747 (SEK26 206)* UK healthcare perspective Healthcare costs 15 628 15 084 545 QALYs 8. German and Brazilian healthcare system per- Brazilian (figure 5B) analyses. €4419 and €4471 from impact on the cost effectiveness results. ness ratio of €3041.7 QALY.16 €3395 (£2920)* German healthcare perspective Healthcare costs 24 186 23 448 739 QALYs 8. Sensitivity analyses The alternative scenarios showed that altering the value of input DISCUSSION parameters not associated with sampling uncertainty (and hence The results show that treatment with ticagrelor is associated not varied in the probabilistic sensitivity analysis) had minor with a cost per QALY of €2747. UK. €3395. Germany and Brazil. there were small differences in agement.44 0. respectively. The curves indicate a high prob.101:119–125. from a Swedish perspective. €3987 and €3958 for Sweden. quality-adjusted life-year. €3132. UK (figure 3B).13 €4471 (BRL10417)* *Cost per QALY in local currency. quality-adjusted life-year.17 €4419 Brazilian public healthcare perspective Healthcare costs 5855 5292 563 QALYs 6. et al. An alternative scenario based 3A. From a Swedish and UK perspective this indicate a high probability that the cost effectiveness ratio of analysis was not performed as the daily cost of clopidogrel is ticagrelor is below conventional threshold values for cost effect- close to zero in the base-case analysis. indicating that ticagrelor is asso. Applying a clopidogrel the perspectives of the Swedish. In accordance with the iveness in patients with ACS scheduled for non-invasive man- results reported by Nikolic et al.93 8. German and Brazilian cost of €0 per day yielded a cost per QALY gained with ticagre.60 8.1722). economics and global health Table 3 Long-term cost-effectiveness results (€) Ticagrelor Clopidogrel Incremental Cost per QALY Swedish healthcare perspective Healthcare costs 35 910 35 443 467 QALYs 9. respectively. (incremental costs €762 and incremental QALY 0.76 0. on the recently published PLATO subpopulation with ness results. UK. healthcare systems. doi:10.

101:119–125. from a UK perspective. quality-adjusted life-year.93 study examined patients with planned non-invasive manage- for clopidogrel-treated patients in the non-invasive cohort com. There were also large differences in life scheduled for non-invasive management was 1.3 4 many patients comparable result for the full PLATO sample was 0. stroke. inhabitants of with 1. based on disease burden. substantially higher than in overall PLATO population7 that the cost effectiveness of ticagre- the overall PLATO sample (5.19 The gross national income per capita (2012 figures) is Patients scheduled for non-invasive management were older. and renal and peripheral artery disease compared capita were substantially higher in Sweden ($4158). the present analysis reveals that the group sched. there are also those scheduled for invasive management. the UK with patients which were scheduled for invasive management. the UK. To achieve this we used ical benefits of evolving medical therapy in this setting. QALY. ive treatment as indicated by the 0. compared with Brazil factors such as diabetes. the UK more often women. All four countries have fully developed and uni- non-ST-elevation ACS were intended for non-invasive manage.6 ($3495) and Germany ($4617) than in Brazil ($1109) according The absolute risk reduction in all-cause mortality in the group to WHO 2012 figures. et al.13.6 In input data from Sweden. This is an interesting from PLATO in patients undergoing non-invasive management Figure 4 (A) Cost effectiveness plane and (B) cost effectiveness acceptability curve. found small differences in clinical event rates.18 although this was substantial differences between the countries as noted by probably related to their increased risk profile at baseline. the UK and Germany can expect to live on average Interestingly.1%. ment. 9 years longer in 2011 compared with Brazil (82 years vs uled for non-invasive management appears to have a relatively 73 years). The present analysis shows lor appears robust in different subgroups. Notably. this of life in the cohort analysed in this study compared with previ.17 gain in QALYs with tica- Although early invasive management is generally recom.7 years in full health.7 In particular. At birth. almost three to four times larger in Sweden ($43 980). this population did in fact include patients who subse- pared with 9. doi:10. group of patients with ACS should (at least) be given the same ously reported subgroups. heart ($11 530) and the government expenditures on health per failure. These patients had higher long-term event rates than central and state/provincial authorities.3% in the overall PLATO sample. grelor in non-invasive patients from a Swedish perspective.9%). and more often had cardiovascular risk ($37 340) and Germany ($42 230). In the clopidogrel group. Heart 2015. although the that this translates into a quality-adjusted life-expectancy of 8. a mended for moderate-to-high-risk patients. economics and global health Figure 3 (A) Cost effectiveness plane and (B) cost effectiveness acceptability curve. with NSTE-ACS continue to be managed conservatively due to A secondary aim of the present study was to investigate how unavailability of early invasive procedures in many countries. differences in healthcare systems and life expectancy may influ- The experience of use of ticagrelor in PLATO indicates the clin. previous myocardial infarction.63 in the full PLATO sample. The clinical results difference of 0. corresponding to a quently underwent coronary intervention. However.20 severe disease burden. ence the cost effectiveness of ticagrelor.7 Sweden. Healthcare delivery.1136/heartjnl-2014-305864 123 . quality-adjusted life-year.7% compared expectancies between the countries. from a German perspective. Janzon M. attention as other groups of patients with ACS. 28% of all patients and 37% of those with present study. costs and quality finding in itself and suggests that. Germany and Brazil in the PLATO. the difference in mor.6 WHO. The severity of tality rates between ticagrelor and clopidogrel after 12 months disease also implies that there may be more to gain from effect- of therapy account for most of the gain in QALYs. QALY. versal public healthcare systems funded and administered by ment. the estimated The present analyses also support the conclusion in the 12-month mortality rate was 8.

101:119–125. Linköping University. These values are below conventional is TRILOGY-ACS. UK. Department of Medical and Health Sciences. He is also responsible for the accuracy of data and integrity of the study. conventional thresholds of cost effectiveness. Ticagrelor has been shown to reduce the cost effectiveness results as the base-case analysis in this study. from a Brazilian perspective. review and final approval of the manuscript. Sweden 4 from the public insurance system are invariably lower than in Thrombolysis in Myocardial Infarction (TIMI) Study Group. USA the private sector. life-year gained with ticagrelor compared with generic economic literature focuses on patients undergoing coronary clopidogrel was €2747.25 The reason for applying only the Center for Medical Technology Assessment. Mölndal.CM: contributed to data analysis. driven by reduced mortality with ticagrelor over clopidogrel. in certain regions of the country) have an additional private Linköping University. Healthcare delivery. interpretation of results. and drafting. Limitations The current analysis took a public healthcare perspective. Sweden public healthcare perspective and not the private one was the 3 Department of Medical Sciences. over clopidogrel in patients aged <75 years (n=7243) and patients aged ≥75 years (n=2083). and is primarily review and final approval of the manuscript. AstraZeneca Nordic-Baltic. One study of interest perspective. Most of these patients were main.1136/heartjnl-2014-305864 . since ticagrelor is associated with 5 Department of Cardiovascular Science. Sheffield. ing the cost effectiveness of ticagrelor that the main driver is the clinical results during the 12 months on dual antiplatelet What might this study add? therapy. similar Key messages findings have recently been reported specifically in the PLATO subpopulation with non-ST-elevation ACS. Twelve months treatment with ticagrelor should be considered tained on a non-invasive strategy after randomisation (only 571 in patients with ACS scheduled for non-invasive management as aged <75 years subsequently underwent coronary intervention). data effectiveness compared with generic clopidogrel. Linköping. Heart 2015. The authors also thank David Evans Treatment of patients with ACS scheduled for 12 months’ non. (Gardiner-Caldwell Communications) who provided medical writing support funded invasive management with ticagrelor is associated with a cost by AstraZeneca. data collection. doi:10. et al. 6 AstraZeneca R&D. €4419 and €4471 from a intervention. University of Sheffield. recruitment. In the subpopulation of patients with ACS who were scheduled Although many patients with non-ST-elevation ACS are for non-invasive management. quality-adjusted life-year.2 21–23 much of the existing health. RFS. Massachusetts. Sweden 2 Division of Health Care Analysis. However. Sweden 7 tive (see online supplementary table S3). German and Brazilian public healthcare system compare and contrast the present findings. appears to be generalisable across different healthcare settings SJ. This finding analysis. The unit costs Uppsala University.24 which showed no superiority of prasugrel thresholds for cost effectiveness. Uppsala.6 Furthermore. review and final approval of the manuscript. this finding only reiterates the previous conclusions regard- patients. however. JCN and LW: contributed to study design. the cost per quality-adjusted managed non-invasively. interpretation of results. Boston. remained in favour of ticagrelor regardless of whether revascu- larisation took place post randomisation. respectively. in Brazil about 25% of the population (reaching 40% Department of Cardiology and Department of Medical and Health Sciences. 124 Janzon M. São Paulo. lack of uniformity among the private unit costs. Brazil 8 private perspective would likely improve the result. Linköping. and countries with different life expectancies. data collection. Brigham and Women’s Hospital and Harvard Medical School. per QALY gained below conventional threshold values of cost Contributors MJ: contributed to study design. University of São Paulo Medical School.17 A sensitivity recommended for 12 months in patients with non-ST-elevation analysis of the subpopulation with non-ST-elevation ACS who acute coronary syndromes (ACS) not undergoing invasive had no revascularisation during the first 10 days showed similar management. the analysis from a Heart Institute (InCor). with non-ST-elevation ACS How might this impact on clinical practice? treated for up to 30 months. with benefit of tica- What is known on this subject? grelor over clopidogrel remaining independent of actually per- Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is formed revascularisation during the first 10 days. CPC. Sweden Acknowledgements The authors thank Dr Tony Piha (AstraZeneca Brazil) for his CONCLUSIONS contribution of Brazilian input data. recruitment. UK lower healthcare costs (excluding drug) from a public perspec. and drafting. healthcare insurance plan. Södertälje. Cardiology and Uppsala Clinical Research Center. €3395. Author affiliations 1 However. and there is a paucity of data with which to Swedish. economics and global health Figure 5 (A) Cost effectiveness plane and (B) cost effectiveness acceptability curve. QALY. improved health outcomes can be achieved at a cost below The economic implications of these findings were not evaluated. In incidence of ischaemic events relative to clopidogrel in these fact.

http://www. and American College of Cardiology Foundation/American Heart Association Task Force drafting.who. 1997. Boehringer-Ingelheim.32:2999–3054. Regeneron. http://sdw. build upon this work non-commercially. 5 Wallentin L.bcb. trends. et al. Merck. Armstrong PW.121:853–62. Kaul P. Merck. General guidelines for Sanofi-Aventis. JCN: is a consultant for AstraZeneca.lio. syndrome patients with ticagrelor for 12 months: results from the PLATO study. JACC Cardiovasc Interv 2008. consultancy fees from AstraZeneca. Sun LJ. predictors. Heart 2015. SJ: receives institutional research grant from AstraZeneca.34:220–8. received lecture fees from Sanofi. Budaj A. Ticagrelor versus clopidogrel in patients with non-ST-elevation acute coronary syndrome: results from the PLATO trial. AstraZeneca. data analysis. acute coronary licenses/by-nc/4. CPC: research grants/support from Accumetrics. Catheterization And Urgent Intervention Triage Strategy (ACUITY) substudy. Regado Biosciences. Regeneron.162:852–9. Cannon C. http://data. and outcomes of coronary syndromes who have angiographically documented significant coronary acute myocardial infarction and percutaneous coronary intervention. Janzon M. clopidogrel in patients with a planned invasive strategy for acute coronary and license their derivative works on different terms. Bayer and BMS. AstraZeneca.101:119–125. Sanofi. Terumo Inc. Diaz R. conservative medical management for patients with non-ST-segment elevation acute 22 Roe MT. on advisory boards for Alnylam. 9 Brazilian Central Bank: exchange rates.worldbank. Bristol-Myers PEguidelines/countrydet. 3 Hamm CW. Bayer and Novartis. 2 Chan MY. http://www. Competing interests MJ: Lecture fees from AstraZeneca. economics and global health MH: contributed to study design. Circulation 2013. honoraria from AstraZeneca. Society of Cardiology (ESC).ecb. 2012 ACCF/AHA focused update coronary syndromes without revascularization. Statistical Data Warehouse: exchange rates. 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