Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study

Christopher P. Cannon, Robert A. Harrington, Stefan James, Diego Ardissino, Richard C. Becker, Håkan Emanuelsson, Steen Husted, Hugo Katus, M. Keltai, Nardev S. Khurmi, Frederic Kontny, Basil S. Lewis, Philippe Gabriel Steg, Robert F. Storey, Daniel Wojdyla, Lars Wallentin

Research output: Contribution to journalArticle

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Abstract

Background: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. Methods: At randomisation, an invasive strategy was planned for 13 408 (72·0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872. Findings: 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9·0%] vs 668 [10·7%], hazard ratio 0·84, 95% CI 0·75-0·94; p=0·0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11·6%] vs 689 [11·5%], 0·99 [0·89-1·10]; p=0·8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3·2%] vs 185 [2·9%], 0·91 [0·74-1·12]; p=0·3785). Interpretation: Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned. Funding: AstraZeneca.

Original languageEnglish
Pages (from-to)283-293
Number of pages11
JournalThe Lancet
Volume375
Issue number9711
DOIs
Publication statusPublished - 2010

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clopidogrel
Acute Coronary Syndrome
Double-Blind Method
Placebos
Hemorrhage
Intention to Treat Analysis
Ticagrelor
(1,2-diamino-4-nitrobenzene)dichloroplatinum(II)
Random Allocation
Aspirin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cannon, C. P., Harrington, R. A., James, S., Ardissino, D., Becker, R. C., Emanuelsson, H., ... Wallentin, L. (2010). Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. The Lancet, 375(9711), 283-293. https://doi.org/10.1016/S0140-6736(09)62191-7

Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO) : a randomised double-blind study. / Cannon, Christopher P.; Harrington, Robert A.; James, Stefan; Ardissino, Diego; Becker, Richard C.; Emanuelsson, Håkan; Husted, Steen; Katus, Hugo; Keltai, M.; Khurmi, Nardev S.; Kontny, Frederic; Lewis, Basil S.; Steg, Philippe Gabriel; Storey, Robert F.; Wojdyla, Daniel; Wallentin, Lars.

In: The Lancet, Vol. 375, No. 9711, 2010, p. 283-293.

Research output: Contribution to journalArticle

Cannon, CP, Harrington, RA, James, S, Ardissino, D, Becker, RC, Emanuelsson, H, Husted, S, Katus, H, Keltai, M, Khurmi, NS, Kontny, F, Lewis, BS, Steg, PG, Storey, RF, Wojdyla, D & Wallentin, L 2010, 'Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study', The Lancet, vol. 375, no. 9711, pp. 283-293. https://doi.org/10.1016/S0140-6736(09)62191-7
Cannon, Christopher P. ; Harrington, Robert A. ; James, Stefan ; Ardissino, Diego ; Becker, Richard C. ; Emanuelsson, Håkan ; Husted, Steen ; Katus, Hugo ; Keltai, M. ; Khurmi, Nardev S. ; Kontny, Frederic ; Lewis, Basil S. ; Steg, Philippe Gabriel ; Storey, Robert F. ; Wojdyla, Daniel ; Wallentin, Lars. / Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO) : a randomised double-blind study. In: The Lancet. 2010 ; Vol. 375, No. 9711. pp. 283-293.
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AU - Cannon, Christopher P.

AU - Harrington, Robert A.

AU - James, Stefan

AU - Ardissino, Diego

AU - Becker, Richard C.

AU - Emanuelsson, Håkan

AU - Husted, Steen

AU - Katus, Hugo

AU - Keltai, M.

AU - Khurmi, Nardev S.

AU - Kontny, Frederic

AU - Lewis, Basil S.

AU - Steg, Philippe Gabriel

AU - Storey, Robert F.

AU - Wojdyla, Daniel

AU - Wallentin, Lars

PY - 2010

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N2 - Background: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. Methods: At randomisation, an invasive strategy was planned for 13 408 (72·0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872. Findings: 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9·0%] vs 668 [10·7%], hazard ratio 0·84, 95% CI 0·75-0·94; p=0·0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11·6%] vs 689 [11·5%], 0·99 [0·89-1·10]; p=0·8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3·2%] vs 185 [2·9%], 0·91 [0·74-1·12]; p=0·3785). Interpretation: Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned. Funding: AstraZeneca.

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