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Real-World Comparison of Clopidogrel, Prasugrel and Ticagrelor in Patients Undergoing Primary Percutaneous Coronary Intervention

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Real-World Comparison of Clopidogrel, Prasugrel and Ticagrelor in Patients Undergoing Primary Percutaneous Coronary Intervention Open access Interventional cardiology Open Heart: first published as 10.1136/openhrt-2018-000951 on 29 June 2019. Downloaded from Real-world comparison of clopidogrel, prasugrel and ticagrelor in patients undergoing primary percutaneous coronary intervention Arvindra Krishnamurthy, 1,2 Claire Keeble,1 Michelle Anderson,2 Kathryn Somers,2 Natalie Burton-Wood,2 Charlotte Harland,2 Paul Baxter,1 Jim McLenachan,2 Jonathan Blaxill,2 Daniel J Blackman,2 Christopher Malkin,2 Stephen Wheatcroft,1,2 John Greenwood1,2 To cite: Krishnamurthy A, ABSTRACT Key questions Keeble C, Anderson M, et al. Background There is a paucity of real-world outcome Real-world comparison of data comparing clopidogrel, prasugrel and ticagrelor in clopidogrel, prasugrel and What is already known about this subject? primary percutaneous coronary intervention (PPCI) for ticagrelor in patients undergoing Ticagrelor and prasugrel have both been shown to ST-segment elevation myocardial infarction (STEMI). We ► primary percutaneous coronary be beneficial when used in patients with acute cor- sought to assess the association of choice of oral P2Y12- intervention. Open Heart onary syndromes. However, there is little available receptor inhibitor with clinical outcomes following PPCI for 2019;6:e000951. doi:10.1136/ data to guide clinicians in choosing between these openhrt-2018-000951 STEMI in a large consecutive patient series. newer agents in primary percutaneous coronary in- Methods Demographic, procedural and 12-month tervention (PPCI). outcome data were prospectively collected for all patients Received 12 October 2018 undergoing PPCI in Leeds, UK, between 01 January 2009 Accepted 30 May 2019 What does this study add? and 31 December 2011, and 01 January 2013 and 31 ► The main finding of this study was that prasugrel December 2013. Clinical endpoints were 30-day and was associated with lower risk-adjusted mortality 12-month all-cause mortality, recurrent MI and 30-day compared with both clopidogrel and ticagrelor, in HORIZONS-major bleeding. Logistic regression analyses patients undergoing PPCI. Both prasugrel and tica- were undertaken to adjust for confounding factors. grelor were associated with lower recurrent myo- http://openheart.bmj.com/ Results Prasugrel (n=1244) was associated with lower cardial infarction compared with clopidogrel. There adjusted 30-day (OR 0.53 (0.34–0.85)) and 12-month were no significant differences in bleeding among (OR 0.55 (0.38–0.78)) mortality, and 12-month MI (OR the three groups. 0.63 (0.42–0.94)) compared with clopidogrel (n=1648). Importantly, prasugrel was associated with lower adjusted How might this impact on clinical practice? 30-day mortality (OR 0.51 (0.29–0.91)) compared with ► The findings of this study suggest that the use of ticagrelor (n=811). Lower 30-day (OR 0.40 (0.17–0.94)) prasugrel and ticagrelor in PPCI could lead to im- and 12-month (OR 0.54 (0.32–0.93)) MI were observed proved outcomes compared with clopidogrel. The in ticagrelor compared with clopidogrel, an association difference in outcomes noted between prasugrel absent in comparison with prasugrel. Adjusted bleeding and ticagrelor may influence prescribing choice in on October 4, 2021 by guest. Protected copyright. were not statistically significantly different among the selected patients, until further data are published P2Y12-receptor inhibitors. from randomised controlled trials. Conclusion In this large consecutive real-world series, © Author(s) (or their prasugrel was associated with lower adjusted 30-day employer(s)) 2019. Re-use mortality compared with ticagrelor and clopidogrel, The addition of oral platelet P2Y12 ADP permitted under CC BY-NC. No and lower adjusted 12-month mortality compared with commercial re-use. See rights receptor inhibitors to aspirin has been and permissions. Published clopidogrel. Both prasugrel and ticagrelor were associated shown to significantly reduce adverse events by BMJ. with lower recurrent MI following PPCI compared with following PCI.3–6 Therefore, dual-antiplatelet 1 clopidogrel, with no overall increase in adjusted bleeding. Leeds Institute of therapy (DAPT) in PPCI for STEMI has been Cardiovascular and Metabolic recommended for use periprocedurally and Medicine, University of Leeds, postprocedurally up to a minimum of 12 Leeds, UK 1 2 7 2Department of Cardiology, INTRODUCTION months. Despite evidence of significant Leeds General Infirmary, Leeds, Primary percutaneous coronary intervention difference in platelet reactivity in patients UK (PPCI) is the guideline-recommended treat- treated with prasugrel compared with tica- ment strategy for patients presenting with grelor, there have been only two observational Correspondence to Dr Arvindra Krishnamurthy; ST-segment elevation myocardial infarction studies and one meta-analysis comparing 1 2 arvindra@ doctors. org. uk (STEMI). clinical outcomes of patients treated with Krishnamurthy A, et al. Open Heart 2019;6:e000951. doi:10.1136/openhrt-2018-000951 1 Open Heart Open Heart: first published as 10.1136/openhrt-2018-000951 on 29 June 2019. Downloaded from prasugrel with clinical outcomes of patients treated with on guideline recommendations at the time of index ticagrelor in STEMI, with contrasting results.8–11 In terms PPCI. Either bivalirudin or unfractionated heparin (±bail of randomised controlled trials (RCTs), the PRAGUE-18 out glycoprotein IIb/IIIa inhibitor) were administered study which aimed to compare prasugrel with ticagrelor during PPCI. Arterial access site, choice of stent (drug- was terminated early due to futility and ISAR-REACT 5 is eluting stent (DES) or bare-metal stent (BMS)) and still ongoing.12 13 aspiration thrombectomy were at the operator’s discre- The aim of this prospective outcomes study was to tion. Thrombolysis in MI (TIMI) classification was used obtain ‘real-world’ data from a large consecutive patient to grade preprocedure and postprocedure flow in the series, to facilitate comparison of clinical outcomes of infarct-related artery. Call-for-help time (call time) and patients treated with clopidogrel, prasugrel and tica- time of patient arrival at LGI (door time) were obtained grelor when undergoing PPCI. either from the ambulance reports or if patients self-pre- sented from the emergency department triage notes. Time to first interventional device (balloon time) was METHODS obtained from the electronic cardiac catheter laboratory The West Yorkshire PPCI Outcome Study was estab- report. Patients were observed on the coronary care unit lished as a prospective, observational study to ascertain post-PPCI for a minimum of 24 hours, and remained in procedural and demographic characteristics, and clinical the hospital for a minimum of 72 hours (either at LGI if outcomes in all patients undergoing PPCI for STEMI at patients were local, or re-patriated to the nearest district Leeds General Infirmary (LGI), UK. LGI is the largest general hospital after a minimum of 6 hours observa- single-centre PPCI centre by volume in the UK, providing tion). DAPT, statin therapy, beta-adrenergic receptor a 24/7 PPCI service to a catchment population of 3.2 blockers, ACE inhibitors (or angiotensin II receptor million people. The period of recruitment was from 1st blockers) and (if indicated) mineralocorticoid receptor of January 2009 until 31st of December 2011, and 1st of antagonists were prescribed according to guideline January 2013 until 31st of December 2013 (4 calendar recommendation. years). Patients who presented between 01 January 2012 and 31 December 2012 were not included as follow-up, Follow-up and data input were not possible due to limited staff avail- Written and electronic case notes were reviewed at ability at the time. the time of discharge to ascertain patient character- Primary endpoints were 30-day and 12-month all-cause istics, procedural variables and in-hospital outcomes. mortality. Secondary endpoints were 30-day and 12-month Drug therapy and adverse events were identified up to MI, and 30-day major bleeding by HORIZONS criteria14 a minimum of 12 months following index PPCI by a (defined as intracranial or intraocular bleeding; access combination of patient telephone contact, accessing site bleeding of diameter of ≥5 cm, or requiring inter- clinical information via written or electronic hospital http://openheart.bmj.com/ vention; a reduction in haemoglobin of ≥40 g/L without records or from the responsible primary care physician. an overt source of bleeding, or ≥30 g/L with an overt Mortality data up to a minimum of 12 months post-PPCI source of bleeding; re-operation for bleeding and blood were obtained from the Office of National Statistics and transfusion). central National Health Service (NHS) records. The Patients who presented with chest pain consistent Myocardial Infarction National Audit Project (MINAP) with myocardial ischaemia for a minimum of 20 min database (database with information pertaining to all with ST-segment elevation of ≥1 mm in contiguous limb patients admitted acutely into NHS hospitals in England leads and/or ≥2 mm in contiguous chest leads, or with and Wales with unstable angina, non-STEMI and STEMI) on October 4, 2021 by guest. Protected copyright. presumed new left bundle branch block on a 12-lead was used to identify MIs. Review of hospital discharge and ECG were diagnosed with STEMI and were included clinic letters, and hospital electronic pathology servers in this study. Patients were transferred by paramedics (for a rise in creatine kinase and/or troponin, and drops directly to the cardiac
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