Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non–ST-segment elevation acute coronary syndrome in the PLATO trial

on behalf of the PLATO Investigators

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Hypothesis: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. Methods: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. Results: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. Conclusions: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

Original languageEnglish (US)
Pages (from-to)390-398
Number of pages9
JournalClinical Cardiology
Volume40
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

clopidogrel
Acute Coronary Syndrome
Safety
Angiography
Random Allocation
Purinergic P2Y Receptor Antagonists
Hemorrhage
Ticagrelor
(1,2-diamino-4-nitrobenzene)dichloroplatinum(II)
Proportional Hazards Models

Keywords

  • Angiography
  • Antiplatelet Therapy
  • Clopidogrel
  • Non–ST-Segment Elevation Acute Coronary Syndromes (NSTE-ACS)
  • P2Y Receptor Antagonists
  • Ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non–ST-segment elevation acute coronary syndrome in the PLATO trial. / on behalf of the PLATO Investigators.

In: Clinical Cardiology, Vol. 40, No. 6, 01.06.2017, p. 390-398.

Research output: Contribution to journalArticle

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title = "Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non–ST-segment elevation acute coronary syndrome in the PLATO trial",
abstract = "Background: Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Hypothesis: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. Methods: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. Results: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95{\%} confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. Conclusions: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.",
keywords = "Angiography, Antiplatelet Therapy, Clopidogrel, Non–ST-Segment Elevation Acute Coronary Syndromes (NSTE-ACS), P2Y Receptor Antagonists, Ticagrelor",
author = "{on behalf of the PLATO Investigators} and Pollack, {Charles V.} and Farideh Davoudi and Diercks, {Deborah B.} and Becker, {Richard C.} and James, {Stefan K.} and Lim, {Soo Teik} and Schulte, {Phillip J.} and Jindrich Spinar and Steg, {Philippe Gabriel} and Storey, {Robert F.} and Anders Himmelmann and Lars Wallentin and Cannon, {Christopher P.}",
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T1 - Relative efficacy and safety of ticagelor vs clopidogrel as a function of time to invasive management in non–ST-segment elevation acute coronary syndrome in the PLATO trial

AU - on behalf of the PLATO Investigators

AU - Pollack, Charles V.

AU - Davoudi, Farideh

AU - Diercks, Deborah B.

AU - Becker, Richard C.

AU - James, Stefan K.

AU - Lim, Soo Teik

AU - Schulte, Phillip J.

AU - Spinar, Jindrich

AU - Steg, Philippe Gabriel

AU - Storey, Robert F.

AU - Himmelmann, Anders

AU - Wallentin, Lars

AU - Cannon, Christopher P.

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N2 - Background: Guidelines suggest that “upstream” P2Y12 receptor antagonists should be considered in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS). Hypothesis: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. Methods: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of “early” (<3h) vs “late” (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. Results: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. Conclusions: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

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KW - Antiplatelet Therapy

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KW - Non–ST-Segment Elevation Acute Coronary Syndromes (NSTE-ACS)

KW - P2Y Receptor Antagonists

KW - Ticagrelor

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