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Heart. 2014 Nov;100(22):1762-9. doi: 10.1136/heartjnl-2014-305619. Epub 2014 Jun 23.

Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes.

Author information

1
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
2
Department of Cardiac and Thoracic Anaesthesia and Surgery, Uppsala University, Uppsala, Sweden.
3
Department of Cardiology, Lund University, Lund, Sweden.
4
Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
5
Department of Medicine, Stanford University, Stanford, California, USA.
6
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
7
TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
8
AstraZeneca R&D, Mölndal, Sweden.

Abstract

OBJECTIVE:

To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.

METHODS:

In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor significantly reduced rates of vascular and total death compared with clopidogrel. In the 905 patients who died postenrolment in the PLATO trial (n=18 624), reviewers, blinded to study treatment, subclassified direct causes of death and evaluated whether infection or bleeding events contributed to fatal events.

RESULTS:

Among vascular deaths, there were significantly fewer sudden deaths (63 (0.7%) vs 98 (1.1%), p<0.01) but no significant difference in deaths caused by acute myocardial infarction (179 (1.9%) vs 194 (2.1%), p=0.43) or heart failure (31 (0.3%) vs 42 (0.5%), p=0.20) with ticagrelor compared with clopidogrel. For non-vascular deaths, there was no difference between treatments in deaths directly caused by infection. Although, patients treated with ticagrelor were at lower risk for death where infection was either a direct cause or contributed to death (51 (0.5%) vs 76 (0.8%), HR 0.67 (0.47 to 0.95), p<0.05) but not for bleeding (42 (0.5%) vs 42 (0.5%), HR 0.99 (0.65 to 1.53), p=0.98).

CONCLUSIONS:

In this post hoc analysis, ticagrelor compared with clopidogrel reduced total and cardiovascular mortality, which appeared to be mainly mediated by a reduction in sudden death. Importantly, bleeding causing or contributing to death did not differ between treatments.

CLINICAL TRIAL REGISTRATION NUMBER:

NCT00391872 (http://www.clinicaltrial.gov).

KEYWORDS:

Coronary Artery Disease; Infection

PMID:
24957530
DOI:
10.1136/heartjnl-2014-305619
[Indexed for MEDLINE]

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