title: Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis.
abstract: BACKGROUND
  Acute 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.
  
  
  OBJECTIVE
  The 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.
  
  
  METHODS
  Four 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.
  
  
  METHODS
  Clinical 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.
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  Lack 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.
  
  
  CONCLUSIONS
  A 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.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42013005047.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Janette
authors.initials: J
authors.lastname: Greenhalgh
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bagust
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Boland
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Kerry
authors.initials: K
authors.lastname: Dwan
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Beale
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Fleeman
authors.affiliation: North West Medicines Information Centre, Pharmacy Practice Unit, Liverpool, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: McEntee
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Yenal
authors.initials: Y
authors.lastname: Dundar
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: Marty
authors.initials: M
authors.lastname: Richardson
authors.affiliation: The Institute for Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital, Liverpool, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D006801:Humans; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride