Background
Clopidogrel in combination with aspirin after acute coronary syndromes (ACS) reduces
recurrent ischaemic events compared to aspirin alone. Further reductions in events
have been demonstrated when clopidogrel is replaced by ticagrelor or prasugrel albeit
with increases in bleeding. There are few studies documenting the patterns of use
of P2Y12 inhibitors or their association with outcomes in the Australian population.
Aims
To describe the patterns of use of each P2Y12 inhibitor and to determine the associations
between initial P2Y12 inhibitor use and outcomes.
Methods
Data were extracted from Cooperative National Registry of ACS, Guideline Adherence
and Clinical Events (CONCORDANCE)—a prospective database of patients presenting to
43 sites across Australia with ACS. Patients were stratified based on first antiplatelet
agent received. Baseline clinical characteristics were compared between these patient
groups and hospital investigations, management as well as in-hospital and 12 months
outcomes (death, a composite of cardiac-related death, myocardial infarction, and
stroke, and major bleeding) were compared between the three treatment cohorts after
adjustment for differences in baseline characteristics.
Results
Mean ages of the clopidogrel (n=7,537), ticagrelor (n=1,878), and prasugrel (n=347)
cohorts were 65, 63, and 58 yrs respectively (p<0.0001), the mean Global Registry
of Acute Coronary Events (GRACE) risk scores were 107, 104, and 102 (p=0.0016). The
ticagrelor and prasugrel cohorts were more likely to receive percutaneous coronary
intervention (PCI) (clopidogrel 52%, ticagrelor 66%, prasugrel 88%, p<0.0001), and
evidence based medications (≥4 guideline indicated medications: clopidogrel 76%, ticagrelor
82%, prasugrel 93%, p<0.0001). Patients treated with ticagrelor and prasugrel were
less likely to experience in-hospital death (clopidogrel 2.5%, ticagrelor 1.4%, prasugrel
1.2%, p=0.05), major adverse cardiac events (MACE) (clopidogrel 5.1%, ticagrelor 3.0%,
prasugrel 3.5% [p=0.01]), or bleeding (clopidogrel 8.4%, ticagrelor 4.6%, prasugrel
7.5% [p<0.001]) compared to clopidogrel. These differences were no longer apparent
after multivariable adjustment. There was no difference in outcomes between cohorts
at 12 months.
Conclusions
In Australia, ticagrelor and prasugrel are used in younger patients who are more likely
to undergo percutaneous coronary intervention (PCI) and receive evidence based therapy.
Patients receiving clopidogrel were more likely to experience in hospital ischaemic
or bleeding events but this was explained by their higher baseline risk. Selection
of therapy was not associated with any difference in outcomes at 12-month follow-up,
but our findings suggest there is room for improvement towards guideline-driven usage
of P2Y12 inhibitors.
Keywords
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References
- Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T113862, ST-elevation myocardial infarction; [updated 2020 Feb 19, cited 2020 Jun 18].(Available from)
- Antiplatelet agents in acute non-ST elevation acute coronary syndromes [updated 2020 May 29, cited 2020 Jun 18]. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA.(Available from)
- Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.BMJ. 2002; 324: 71-86
Australian Medicines Handbook 2020 [online]. Adelaide: Australian Medicines Handbook Pty Ltd; 2020. Blood and Electrolytes: P2Y12 antagonists.
- Effects of Clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation (CURE).N Engl J Med. 2001; 345: 494-502
- Addition of Clopidogrel to aspirin in 45,852 patients with acute myocardial infarction (COMMIT): randomised placebo-controlled trial.Lancet. 2005; 366: 1607-1621
- Prasugrel versus Clopidogrel in patients with acute coronary syndromes (TRITON).N Engl J Med. 2007; 357: 2001-2015
- Ticagrelor versus clopidogrel in patients with acute coronary syndromes (PLATO).N Engl J Med. 2009; 361: 1045-1057
- Brilinta (Ticagrelor): Full Prescribing Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE 198502011 (Revised Sept 2016)
- Effient (Prasugrel): Full Prescribing Information. Eli Lilly and Company, Indianapolis IN 462852009 (Revised Mar 2019)
- Plavix (Clopidogrel Bisulfate): Full Prescribing Information. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, Bridgewater NJ 088071997 (Revised May 2019)
- National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016.Heart Lung Circ. 2016; 25: 895-951
- Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-label, non-inferiority trial.Lancet. 2020; 395: 1374-1381
- Ticagrelor or prasugrel in patients with acute coronary syndromes (ISAR-REACT-5).N Engl J Med. 2019; 381: 1524-1534
- Cooperative National Registry of Acute Coronary care, Guideline Adherence and Clinical Events (CONCORDANCE).Heart Lung Circ. 2013; 22: 533-541
- The underutilisation of dual antiplatelet therapy in acute coronary syndrome.Int J Cardiol. 2017; 204: 30-36
- A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation.Chest. 2010 Nov; 138: 1093-1100
- Trends in clinical, demographic, and biochemical characteristics of patients with acute myocardial infarction from 2003 to 2008.J Am Heart Assoc. 2012 July; 1: 1-18
- Prasugrel versus clopidogrel for acute coronary syndromes without revascularisation (TRILOGY-ACS).N Engl J Med. 2012; 367: 1297-1309
- Clopidogrel, prasugrel, or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.Intern Med J. 2016; 46: 559-565
- Contemporary use of ticagrelor in patients with acute coronary syndrome: insights from Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).Eur Heart J Cardiovasc Pharmacother. 2016; 2: 5-12
- Ticagrelor versus clopidogrel in real-world patients with ST elevation myocardial infarction: 1-year results by propensity score analysis.BMC Cardiovasc Disord. 2017; 17: 97-108
- Safety and effectiveness of contemporary P2Y12 inhibitors in an East Asian population with acute coronary syndrome: a nationwide population-based cohort study.J Am Heart Assoc. 2019 Jul, 16; : 8
- Clopidogrel or ticagrelor in acute coronary syndrome patients treated with newer-generation drug-eluting stents: CHANGE-DAPT.EuroIntervention. 2017; 13: 1168-1176
- APT. EuroIntervention. 2017; 13: 1168-1176
- A look at the interaction between opioids and orap P2Y12 inhibitors: Are opioids blocking platelet inhibition?.Cardiol. Today. 2020; (Jan 16)
Article info
Publication history
Published online: May 16, 2022
Accepted:
March 27,
2022
Received in revised form:
December 26,
2021
Received:
October 3,
2021
Identification
Copyright
Crown Copyright © 2022 Published by Elsevier B.V. on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.
