Short term versus long term dual antiplatelet therapy after implantation of drug eluting stent in patients with or without diabetes: systematic review and meta-analysis of individual participant data from randomised trials.
OBJECTIVE
To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes.


METHODS
Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes.


METHODS
Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials.


METHODS
Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat.


RESULTS
Six trials including 11 473 randomised patients were pooled. Of these patients, 3681 (32.1%) had diabetes and 7708 (67.2%) did not (mean age 63.7 (SD 9.9) and 62.8 (SD 10.1), respectively), and in 84 (0.7%) the information was missing. Diabetes was an independent predictor of MACE (hazard ratio 2.30, 95% confidence interval 1.01 to 5.27; P=0.048 At one year follow-up, long term DAPT was not associated with a decreased risk of MACE compared with short term DAPT in patients with (1.05, 0.62 to 1.76; P=0.86) or without (0.97, 0.67 to 1.39; P=0.85) diabetes (P=0.33 for interaction). The risk of myocardial infarction did not differ between the two DAPT regimens (0.95, 0.58 to 1.54; P=0.82; for those with diabetes and 1.15, 0.68 to 1.94; P=0.60; for those without diabetes (P=0.84 for interaction). There was a lower risk of definite/probable stent thrombosis with long term DAPT among patients with (0.26, 0.09 to 0.80; P=0.02) than without (1.42, 0.68 to 2.98; P=0.35) diabetes, with positive interaction testing (P=0.04 for interaction), although the landmark analysis showed a trend towards benefit in both groups. Long term DAPT was associated with higher rates of major or minor bleeding, irrespective of diabetes (P=0.37 for interaction).


CONCLUSIONS
Although the presence of diabetes emerged as an independent predictor of MACE after implantation of a drug eluting stent, compared with short term DAPT, long term DAPT did not reduce the risk of MACE but increased the risk of bleeding among patients with stents with and without diabetes.
Department of Cardiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland.|Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
Giuseppe
G
Gargiulo
Department of Cardiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland.
Stephan
S
Windecker
Department of Cardiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland.|Institute of Primary Health Care (BIHAM), University of Bern, Switzerland.
Bruno R
BR
da Costa
Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.
Fausto
F
Feres
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.
Myeong-Ki
MK
Hong
Department of Cardiology, CHU de la Cavale Blanche, Brest, France.
Martine
M
Gilard
Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
Hyo-Soo
HS
Kim
Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy.
Antonio
A
Colombo
Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
Deepak L
DL
Bhatt
Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.
Byeong-Keuk
BK
Kim
Department of Cardiology, CHU de la Cavale Blanche, Brest, France.
Marie-Claude
MC
Morice
Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea.
Kyung Woo
KW
Park
Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy.
Alaide
A
Chieffo
Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Bologna, Italy.
Tullio
T
Palmerini
Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.
Gregg W
GW
Stone
Department of Cardiology, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland marco.valgimigli@insel.ch.
Marco
M
Valgimigli
D023921:Coronary Stenosis / Q000453:epidemiology / Q000628:therapy; D003328:Coronary Thrombosis / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors