Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis

Abstract

BackgroundAcute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient®, Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique®, AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review.ObjectivesThe remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182.Data sourcesFour electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI.MethodsClinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus.ResultsNo new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS patients scheduled for PCI. No relevant economic evaluations were identified. Our analyses focused on a key subgroup of patients: those aged < 75 years who weighed > 60 kg (no previous stroke or transient ischaemic attack). For the primary composite end point (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) statistically significantly fewer events occurred in the prasugrel arm (8.3%) than in the clopidogrel arm (11%). No statistically significant difference in major bleeding events was noted. However, there was a significant difference in favour of clopidogrel when major and minor bleeding events were combined (3.0 vs. 3.9%). No conclusions could be drawn regarding HRQoL. The results of sensitivity analyses confirmed that it is likely that, for all four ACS subgroups, within 5–10 years prasugrel is a cost-effective treatment option compared with clopidogrel at a willingness-to-pay threshold of £20,000 to £30,000 per QALY gained. At the full 40-year time horizon, all estimates are < £10,000 per QALY gained.LimitationsLack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. The long-term modelling exercise is vulnerable to major assumptions about the continuation of early health outcome gains.ConclusionA key strength of the review is that it demonstrates the cost-effectiveness of prasugrel compared with clopidogrel using the generic price of clopidogrel. Although the report demonstrates the cost-effectiveness of prasugrel compared with clopidogrel at a threshold of £20,000 to £30,000 per QALY gained, the long-term modelling is vulnerable to major assumptions regarding long-term gains. Lack of data precluded a clinical comparison of prasugrel with ticagrelor; the comparative effectiveness of prasugrel compared with ticagrelor therefore remains unknown. Well-audited data are needed from a long-term UK clinical registry on defined ACS patient groups treated with PCI who receive prasugrel, ticagrelor and clopidogrel.Study registrationThis study is registered as PROSPERO CRD42013005047.FundingThe National Institute for Health Research Health Technology Assessment programme.

Bleeding risk in patients prescribed dual antiplatelet therapy and triple therapy after coronary interventions: the ADAPTT retrospective population-based cohort studies

“…TRITON-TIMI 38 was also used to inform a cost-effectiveness modelling study for the UK in which 1-year health-care costs, excluding drug costs, were estimated to be £274 lower among patients with diabetes treated with prasugrel than among those with diabetes treated with clopidogrel. 101 The cost-effectiveness of treating ACS patients with DAPT with ticagrelor for 12 months instead of DAPT with clopidogrel in the Swedish setting was evaluated using data from the PLATO randomised trial. 135 This study found comparable total health-care costs, including the cost of study drugs, between the two treatment strategies (€96, 95% CI -€360 to €553 in 2010 Euros).…”

“…The 12 eligible studies comprised two primary research studies 14,100 (Table 43) and 10 decision-analytic modelling studies [101][102][103][104][105][106][107][108][109][110] (Table 44). Utility decrements from the primary research studies, derived using differences in baseline and 6-month follow-up responses from the EQ-5D-3L, ranged from -0.0257 (95% CI -0.0365 to -0.0148) for minor bleeds to -0.0445 (95% CI -0.073 to -0.016) for major bleeds (see Table 43).…”

“…Comparative effect of different combinations of antiplatelet therapy on total health-care costs: inverse probability-weighted analyses of three population-based cohorts Several studies have compared economic outcomes associated with different antiplatelet regimens among patients undergoing PCI. 101,[121][122][123] One modelling study from the UK estimated the costeffectiveness of clopidogrel and aspirin versus aspirin monotherapy among patients with non-ST segment elevation ACS. 6 However, estimates are lacking for the UK of the cost-effectiveness of using ticagrelor instead of prasugrel for DAPT with patients who undergo PCI or the comparative costeffectiveness of clopidogrel and aspirin versus aspirin monotherapy for patients who undergo CABG or have conservatively managed ACS.…”

“…NIHR Journals Library www.journalslibrary.nihr.ac.uk101 Garg et al102 Kazi et al103 Liew et al104 Gupta et al105 …”

“…See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source -NIHR Journals Library, and the DOI of the publication must be cited 101. Garg et al102 Kazi et al103 Liew et al104 Gupta et al105…”