Competing risks of major bleeding and thrombotic events with prasugrel-based dual antiplatelet therapy after stent implantation - An observational analysis from BASKET-PROVE II.
Adult
Age Factors
Aged
Aged, 80 and over
Aspirin
/ administration & dosage
Drug Therapy, Combination
Drug-Eluting Stents
/ adverse effects
Female
Hemorrhage
/ etiology
Humans
Male
Middle Aged
Platelet Aggregation Inhibitors
/ administration & dosage
Prasugrel Hydrochloride
/ administration & dosage
Proportional Hazards Models
Retrospective Studies
Risk Factors
Stents
/ adverse effects
Thrombosis
/ etiology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
14
08
2018
accepted:
24
12
2018
entrez:
16
1
2019
pubmed:
16
1
2019
medline:
23
10
2019
Statut:
epublish
Résumé
Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.
Sections du résumé
BACKGROUND
Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking.
OBJECTIVES
To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation.
METHODS
Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed.
RESULTS
Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase.
CONCLUSIONS
In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and the competing risk balance necessitating individualized treatment decisions.
Identifiants
pubmed: 30645635
doi: 10.1371/journal.pone.0210821
pii: PONE-D-18-23775
pmc: PMC6333357
doi:
Substances chimiques
Platelet Aggregation Inhibitors
0
Prasugrel Hydrochloride
G89JQ59I13
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0210821Déclaration de conflit d'intérêts
Prasugrel was provided without charge by Eli Lilly Europe, Windlesham, UK, and Daiichy Sankyo Europe, Munich, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Références
J Clin Pharmacol. 2012 Jun;52(6):789-97
pubmed: 21628601
N Engl J Med. 1993 Sep 2;329(10):673-82
pubmed: 8204123
Eur Heart J. 2018 Jan 14;39(3):213-260
pubmed: 28886622
Eur Heart J. 2011 Dec;32(23):2999-3054
pubmed: 21873419
N Engl J Med. 2010 Dec 9;363(24):2310-9
pubmed: 21080780
Circulation. 2013 Aug 20;128(8):823-33
pubmed: 23852610
JAMA. 2013 Mar 13;309(10):1022-9
pubmed: 23483177
Eur Heart J. 2010 Oct;31(20):2501-55
pubmed: 20802248
J Am Coll Cardiol. 2007 Apr 10;49(14):1505-16
pubmed: 17418288
N Engl J Med. 2001 Aug 16;345(7):494-502
pubmed: 11519503
J Am Coll Cardiol. 2007 Mar 27;49(12):1362-8
pubmed: 17394970
Am Heart J. 2014 Nov;168(5):698-705
pubmed: 25440798
N Engl J Med. 2006 Apr 20;354(16):1706-17
pubmed: 16531616
Comput Math Methods Med. 2013;2013:745742
pubmed: 24454541
Circulation. 2015 Jan 6;131(1):74-81
pubmed: 25411159
J Am Coll Cardiol. 2010 Jun 8;55(23):2556-66
pubmed: 20513595
N Engl J Med. 2009 Sep 10;361(11):1045-57
pubmed: 19717846
Circulation. 2006 Aug 22;114(8):774-82
pubmed: 16908769
Circulation. 2007 May 1;115(17):2344-51
pubmed: 17470709
Circulation. 1987 Jul;76(1):142-54
pubmed: 3109764
Am Heart J. 2012 Feb;163(2):136-41.e1
pubmed: 22305828
Eur Heart J. 2003 Oct;24(20):1815-23
pubmed: 14563340
N Engl J Med. 2007 Nov 15;357(20):2001-15
pubmed: 17982182
Am Heart J. 2007 Jul;154(1):3-11
pubmed: 17584547
J Am Coll Cardiol. 2009 Mar 24;53(12):1021-30
pubmed: 19298914
Circulation. 2012 Jan 24;125(3):471-3
pubmed: 22179531
N Engl J Med. 2014 Dec 4;371(23):2155-66
pubmed: 25399658
Circulation. 2005 Jun 28;111(25):3366-73
pubmed: 15967851
Circulation. 2011 Jun 14;123(23):2736-47
pubmed: 21670242