Stent Thrombosis and Dual Antiplatelet Therapy Interruption With Everolimus-Eluting Stents: Insights From the Xience V Coronary Stent System Trials.
BACKGROUND
Whether premature dual antiplatelet therapy (DAPT) interruption is safe in patients receiving cobalt chromium everolimus-eluting stents remains controversial. We sought to examine the relationship between DAPT discontinuation and stent thrombosis (ST) after cobalt chromium everolimus-eluting stents.


RESULTS
Outcomes from 11,219 patients were pooled from 3 randomized trials and 4 registries with 2-year follow-up period after cobalt chromium everolimus-eluting stent implantation. Rates of definite/probable ST were analyzed according to DAPT discontinuation in the following time intervals: 0 to 30, 30 to 90, 90 to 180, 180 to 365, and 365 to 730 days. Eighty-five cases of ST (0.75%) occurred in 83 patients during 2 years, with 41 (48.2%) events occurring within 30 days. The 2-year ST rate in patients interrupting DAPT at any time was similar to that in patients never interrupting DAPT through 2 years (25/4067 [0.63%] versus 58/7152 [0.83%] respectively; P=0.27]. By propensity and DAPT usage-adjusted multivariable analysis, permanent DAPT discontinuation before 30 days was independently associated with the occurrence of ST (hazard ratio [95% confidence interval], 26.8 [8.4-85.4]; P<0.0001), whereas permanent DAPT discontinuation in any interval after 90 days was not associated with ST. Only 2 ST events occurred after DAPT discontinuation between 30 and 90 days (both between 30 and 60 days), and the association between permanent DAPT discontinuation and ST during this period is unclear (hazard ratio [95% confidence interval], 8.7 [2.0-37.3]; P=0.004 for adjusted analysis and 3.4 [0.8-13.8]; P=0.07 for the unadjusted analysis).


CONCLUSIONS
In this large pooled experience, permanent DAPT discontinuation before 30 days after cobalt chromium everolimus-eluting stent implantation was strongly associated with ST, whereas DAPT discontinuation beyond 90 days appeared safe.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180310, NCT00180479, NCT00307047, NCT00402272, NCT00496938, NCT00676520, and NCT00631228.
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Philippe
P
Généreux
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
David R
DR
Rutledge
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Tullio
T
Palmerini
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Adriano
A
Caixeta
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Elvin
E
Kedhi
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
James B
JB
Hermiller
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Jin
J
Wang
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Mitchell W
MW
Krucoff
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Jennifer
J
Jones-McMeans
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Krishnankutty
K
Sudhir
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Charles A
CA
Simonton
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.).
Patrick W
PW
Serruys
From the Columbia University Medical Center, New York, NY (P.G., G.W.S.); Cardiovascular Research Foundation, New York, NY (P.G., G.W.S.); Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada (P.G.); Abbott Vascular, Santa Clara, CA (D.R.R., J.W., J.J.-M., K.S., C.A.S.); Istituto di Cardiologia, University of Bologna, Italy (T.P.); Escola Paulista de Medicina, Universidade Federal de São Paulo and Hospital Israelita Albert Einstein, São Paolo, Brazil (A.C.); Isala Klinieken, Zwolle, the Netherlands (E.K.); St. Vincent Heart Center of Indiana, Indianapolis (J.B.H.); Duke University Medical Center, Durham, NC (M.W.K.); and Erasmus University Hospital, Rotterdam, the Netherlands (P.W.S.). gs2184@columbia.edu.
Gregg W
GW
Stone
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000209:etiology*; D004338:Drug Combinations; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D028761:Withholding Treatment
D004338:Drug Combinations; D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D000068338:Everolimus; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
drug-eluting stents; stents; thrombosis