Citation

Varenhorst C, Alström U, Braun O, Storey RF, Mahaffey KW, Bertilsson M, Cannon CP, Scirica BM, Himmelmann A, James SK, Wallentin L, Held C. Heart 2014; 100(22): 1762-1769.

Copyright

(Copyright © 2014, BMJ Publishing Group)

DOI

10.1136/heartjnl-2014-305619

PMID

unavailable

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 signi ficantly 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). © 2014, BMJ Publishing Group. All rights reserved.

Language: en

Keywords

Humans; Aged; Female; Male; Middle Aged; adult; human; age; Cause of Death; Severity of Illness Index; suicide; female; male; Prospective Studies; Age Factors; Risk Assessment; Sex Factors; multiple organ failure; ischemic heart disease; Time Factors; aged; survival; Proportional Hazards Models; Confidence Intervals; Kaplan-Meier Estimate; liver failure; sex difference; randomized controlled trial; cause of death; mortality; Follow-Up Studies; heart failure; risk assessment; Survival Analysis; comparative study; major clinical study; controlled study; retrospective study; middle aged; bleeding; lung embolism; acetylsalicylic acid; hydroxymethylglutaryl coenzyme A reductase inhibitor; sudden death; cerebrovascular accident; follow up; drug fatality; beta adrenergic receptor blocking agent; acute heart infarction; hypertension; prospective study; diabetes mellitus; infection; heart arrhythmia; brain hemorrhage; time; calcium channel blocking agent; dipeptidyl carboxypeptidase inhibitor; gastrointestinal hemorrhage; cardiovascular risk; heparin; ticlopidine; proton pump inhibitor; confidence interval; thrombosis; urinary tract infection; Article; diuretic agent; dyslipidemia; low molecular weight heparin; angiotensin receptor antagonist; coronary artery bypass graft; clopidogrel; Platelet Aggregation Inhibitors; Ticlopidine; treatment duration; angiocardiography; proportional hazards model; acute coronary syndrome; respiratory tract infection; Kaplan Meier method; fondaparinux; hirulog; cardiogenic shock; surgical infection; thrombocyte aggregation inhibition; severity of illness index; antithrombocytic agent; analogs and derivatives; ST segment elevation myocardial infarction; cardiovascular mortality; peripheral occlusive artery disease; Acute Coronary Syndrome; adenosine; Adenosine; bloodstream infection; fibrinogen receptor antagonist; pleiotropy; ticagrelor