Ticagrelor in Patients with Stable Coronary Disease and Diabetes
Carregando...
Citações na Scopus
262
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
MASSACHUSETTS MEDICAL SOC
Autores
STEG, P. Gabriel
BHATT, Deepak L.
SIMON, Tabassome
FOX, Kim
MEHTA, Shamir R.
HARRINGTON, Robert A.
HELD, Claes
ANDERSSON, Marielle
HIMMELMANN, Anders
RIDDERSTRALE, Wilhelm
Citação
NEW ENGLAND JOURNAL OF MEDICINE, v.381, n.14, p.1309-1320, 2019
Resumo
Patients with stable coronary artery disease and diabetes were randomly assigned to receive either ticagrelor plus aspirin or placebo plus aspirin. At 40 months, the incidence of the composite efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower with ticagrelor than with placebo; the frequency of major bleeding was higher with ticagrelor. Background Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. Methods In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. Results A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P=0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). Conclusions In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).
Palavras-chave
Referências
- Baber U, 2016, AM HEART J, V182, P125, DOI 10.1016/j.ahj.2016.09.006
- Bhatt DL, 2007, NEW ENGL J MED, V357, P2078, DOI 10.1056/NEJMe0706859
- Bhatt DL, 2007, J AM COLL CARDIOL, V49, P1982, DOI 10.1016/j.jacc.2007.03.025
- Bhatt DL, 2019, NEW ENGL J MED, V380, P1825, DOI 10.1056/NEJMoa1901778
- Bhatt DL, 2019, CLIN CARDIOL, V42, P498, DOI 10.1002/clc.23164
- Bhatt DL, 2018, LANCET, V392, P896, DOI 10.1016/S0140-6736(18)31884-1
- Bhatt DL, 2017, J AM COLL CARDIOL, V69, P603, DOI 10.1016/j.jacc.2016.11.050
- Bhatt DL, 2016, J AM COLL CARDIOL, V67, P2732, DOI 10.1016/j.jacc.2016.03.529
- Bhatt DL, 2009, NAT REV CARDIOL, V6, P737, DOI 10.1038/nrcardio.2009.192
- Bhatt DL, 2006, NEW ENGL J MED, V354, P1706, DOI 10.1056/NEJMoa060989
- Bonaca MP, 2015, NEW ENGL J MED, V372, P1791, DOI 10.1056/NEJMoa1500857
- Capodanno D, 2018, NAT REV CARDIOL, V15, P480, DOI 10.1038/s41569-018-0049-1
- Cavender MA, 2015, CIRCULATION, V132, P923, DOI 10.1161/CIRCULATIONAHA.114.014796
- Elmariah S, 2018, CIRC-CARDIOVASC INTE, V11, DOI 10.1161/CIRCINTERVENTIONS.117.005795
- Haffner SM, 1998, NEW ENGL J MED, V339, P229, DOI 10.1056/NEJM199807233390404
- James S, 2010, EUR HEART J, V31, P3006, DOI 10.1093/eurheartj/ehq325
- Krempf M, 2010, AM J CARDIOL, V105, P667, DOI 10.1016/j.amjcard.2009.10.048
- Ferreiro JL, 2011, CIRCULATION, V123, P798, DOI 10.1161/CIRCULATIONAHA.109.913376
- Mauri L, 2014, NEW ENGL J MED, V371, P2155, DOI 10.1056/NEJMoa1409312
- Meredith IT, 2016, CIRCULATION, V133, P1772, DOI 10.1161/CIRCULATIONAHA.115.016783
- Roe MT, 2012, NEW ENGL J MED, V367, P1297, DOI 10.1056/NEJMoa1205512
- Sarwar N, 2010, LANCET, V375, P2215, DOI 10.1016/S0140-6736(10)60484-9
- Steg PG, 2018, CIRCULATION, V137, P1429, DOI 10.1161/CIRCULATIONAHA.117.033442
- Storey RF, 2016, J AM COLL CARDIOL, V67, P1145, DOI 10.1016/j.jacc.2015.12.062
- Thomas MR, 2017, THROMB HAEMOSTASIS, V117, P940, DOI 10.1160/TH16-09-0703
- Udell JA, 2016, EUR HEART J, V37, P390, DOI 10.1093/eurheartj/ehv443
- Vranckx P, 2018, LANCET, V392, P940, DOI 10.1016/S0140-6736(18)31858-0
- Wallentin L, 2009, NEW ENGL J MED, V361, P1045, DOI 10.1056/NEJMoa0904327
- Welsh RC, 2016, AM HEART J, V181, P92, DOI 10.1016/j.ahj.2016.08.008
- Wiviott SD, 2008, CIRCULATION, V118, P1626, DOI 10.1161/CIRCULATIONAHA.108.791061
- Wiviott SD, 2007, NEW ENGL J MED, V357, P2001, DOI 10.1056/NEJMoa0706482
- Wiviott SD, 2013, LANCET, V382, P605, DOI 10.1016/S0140-6736(13)61451-8