Ticagrelor in patients with heart failure after acute coronary syndromes—Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial - 16/06/19

Doi : 10.1016/j.ahj.2019.04.006

Axel Åkerblom, MD, PhD ^a,^b, Daniel M. Wojdyla, MS ^c, Lars Wallentin, MD, PhD ^a,^b, Stefan K. James, MD, PhD ^a,^b, Flávio de Souza Brito, MD ^c, Philippe Gabriel Steg, MD ^d,^e,^f,^g, Christopher P. Cannon, MD ^h, Hugo A. Katus, MD ⁱ, Anders Himmelmann, MD, PhD ^j, Robert F. Storey, MD, DM ^k, Richard C. Becker, MD ^l, Renato D. Lopes, MD, PhD ^c,^{^⁎}
on behalf of the PLATO Investigators
^a Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
^b Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
^c Duke Clinical Research Institute, Duke University Medical Center, Durham, NC
^d Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Paris, France
^e Paris Diderot University, Sorbonne Paris Cité, Paris, France
^f NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK
^g FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, INSERM U1148, Paris, France
^h Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA and Baim Institute, Boston, MA
ⁱ Medizinishe Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany
^j AstraZeneca Research and Development, Gothenburg, Sweden
^k Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
^l Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, Academic Health Center, Cincinnati, OH

^⁎Reprint requests: Renato D. Lopes, MD, PhD, Duke Clinical Research Institute, Duke Medicine, Durham, NC 27710.Duke Clinical Research Institute, Duke MedicineDurhamNC27710

Abstract

Background

Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.

Methods

We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission.

The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.

Results

Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF.

Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).

Conclusions

In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.

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Plan

Methods

Study population and outcomes

HF in relation to outcomes

Effects of ticagrelor versus clopidogrel on CV events according to HF

Factors associated with postdischarge new-onset HF

Effects of ticagrelor versus clopidogrel on new-onset HF

	Trial registration: NCT00391872, NCT00391872.
	Funding: The PLATO study was funded by AstraZeneca. Support for the analysis and interpretation of results and preparation of the manuscript was provided through funds to the Uppsala Clinical Research Center and Duke Clinical Research Institute as part of the Clinical Study Agreement. Dr Anders Himmelmann is an employee of AstraZeneca.
	Javed Butler, MD, MPH, served as guest editor for this article.

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Vol 213

P. 57-65 - juillet 2019 Retour au numéro

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Ticagrelor in patients with heart failure after acute coronary syndromes—Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial - 16/06/19

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