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Randomized Controlled Trial
. 2011 Jun 17:342:d3527.
doi: 10.1136/bmj.d3527.

Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial

Stefan K James  1 , Matthew T Roe, Christopher P Cannon, Jan H Cornel, Jay Horrow, Steen Husted, Hugo Katus, Joao Morais, Ph Gabriel Steg, Robert F Storey, Susanna Stevens, Lars Wallentin, Robert A Harrington; PLATO Study Group
Affiliations
Randomized Controlled Trial

Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial

Stefan K James et al. BMJ. .

Abstract

Objective: To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy.

Design: Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial.

Setting: 862 centres in 43 countries.

Participants: 5216 (28%) of 18,624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management.

Interventions: Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615).

Main outcome measurements: Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year.

Results: 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel.

Conclusions: In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy.

Trial registration: Clinical trials NCT00391872.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request from the corresponding author). SKJ declares research grants and advisory board fees from AstraZeneca and honorariums from AstraZeneca, Bristol-Myers Squibb, Schering-Plough, Merck, and Eli-Lilly. MTR declares research grants from Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, and Merck/Schering-Plough; consulting fees or honorariums from GlaxoSmithKline, Novartis, Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, Merck/Schering-Plough, and AstraZeneca. CPC receives research grants/support from Accumetrics, AstraZeneca, Glaxo-SmithKline, Intekrin Therapeutics, Merck, and Takeda; has served on advisory boards for Bristol-Myers Squibb/Sanofi-Aventis, Novartis, and Alnyam (but donates funds to charity); receives honorariums for development of independent educational symposiums from Pfizer and AstraZeneca; and is a clinical adviser for and holds equity in Automedics Medical Systems. JHC declares consulting fees from Eli Lilly and Pfizer. JH is an employee of AstraZeneca and has equity ownership in AstraZeneca. SH declares research grants from AstraZeneca, Bristol-Myers Squibb, Pfizer, and Bayer and consultant fees from Sanofi-Aventis, Pfizer, and AstraZeneca. HK declares consulting and lecture fees from AstraZeneca., Bayer, Daiichi, Sankoy, and Roche. JM declares research grants from AstraZeneca, Bayer, Daiichi Sankyo, MSD/Schering-Plough, and Eli Lilly. PGS declares research grants from Servier; consultant fees from/advisory board membership for Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi/Sankyo/Eli Lilly alliance, GlaxoSmithKline, Medtronic, Merck, Otsuka Pharmaceutical, Roche, Sanofi-Aventis, Servier, and the Medicines Company; and having equity ownership in Aterovax. RFS declares institutional grants from AstraZeneca, Dynabyte, Eli Lilly/Daiichi Sankyo alliance, Merck/Schering-Plough, and Accumetrics; honorariums from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, Novartis, Medscape, GlaxoSmithKline, and Merck/Schering-Plough; consultant fees from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, Merck/Schering-Plough, Novartis, Sanofi-Aventis/Bristol-Myers Squibb, the Medicines Company, and Accumetrics; travel support from AstraZeneca, Eli Lilly/Daiichi Sankyo alliance, and Merck/Schering-Plough. LW reports research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, and Schering-Plough; honorariums from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, and Eli Lilly; consultant fees from Regado Biotechnologies, Athera Biotechnologies, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, and Eli Lilly; and lecture fees from AstraZeneca, Boehringer Ingelheim, and Eli Lilly. RAH reports advisory board fees from Novartis, Portola Pharmaceutical, and Merck; consulting fees from AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, Portola, and Sanofi-Aventis; honorariums/lecture fees from Eli Lilly, Merck, and AstraZeneca; grant support from AstraZeneca, Bristol-Myers Squibb, Portola Pharmaceutical, and Merck; travel support from AstraZeneca, Novartis, and Merck; and potential grant support from the Medicines Company.

Figures

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Fig 1 Flowchart showing number of patients intended for invasive and non-invasive management at time of randomisation, randomised to ticagrelor or clopidogrel, and final diagnosis at discharge. NSTEMI=non-ST segment myocardial infarction; STEMI=ST segment myocardial infarction
None
Fig 2 Cumulative incidence of cardiac catheterisation, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients intended for non-invasive management and randomised to ticagrelor or clopidogrel
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Fig 3 Cumulative incidence of primary composite of cardiovascular death, myocardial infarction (MI), and stroke in ticagrelor and clopidogrel groups in patients intended for invasive and non-invasive management at time of randomisation
None
Fig 4 Cumulative incidence of total mortality in ticagrelor and clopidogrel groups in patients intended for invasive and non-invasive management at time of randomisation
None
Fig 5 Cumulative incidence of major bleeding in ticagrelor and clopidogrel groups in patients intended for invasive and non-invasive management at time of randomisation
See this image and copyright information in PMC

Comment in

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