Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.
BACKGROUND
Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.


METHODS
Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.


RESULTS
A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.


CONCLUSIONS
Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).
The authors' affiliations are listed in the Appendix.
Laura
L
Mauri
Dean J
DJ
Kereiakes
Robert W
RW
Yeh
Priscilla
P
Driscoll-Shempp
Donald E
DE
Cutlip
P Gabriel
PG
Steg
Sharon-Lise T
SL
Normand
Eugene
E
Braunwald
Stephen D
SD
Wiviott
David J
DJ
Cohen
David R
DR
Holmes
Mitchell W
MW
Krucoff
James
J
Hermiller
Harold L
HL
Dauerman
Daniel I
DI
Simon
David E
DE
Kandzari
Kirk N
KN
Garratt
David P
DP
Lee
Thomas K
TK
Pow
Peter
P
Ver Lee
Michael J
MJ
Rinaldi
Joseph M
JM
Massaro
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000401:mortality / Q000628:therapy; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin