6- Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin: Final Results of the ITALIC Trial (Is There a Life for DES After Discontinuation of Clopidogrel).

The aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is noninferior to 24-month DAPT in aspirin-sensitive patients. The ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented. In a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component. Overall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6- versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding. Two-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT.

Didier R ，Morice MC ，Barragan P ，Noryani AAL ，Noor HA ，Majwal T ，Hovasse T ，Castellant P ，Schneeberger M ，Maillard L ，Bressolette E ，Wojcik J ，Delarche N ，Blanchard D ，Jouve B ，Ormezzano O ，Paganelli F ，Levy G ，Sainsous J ，Carrie D ，Furber A ，Berlan J ，Darremont O ，Le Breton H ，Lyuycx-Bore A ，Gommeaux A ，Cassat C ，Kermarrec A ，Cazaux P ，Druelles P ，Dauphin R ，Armengaud J ，Dupouy P ，Champagnac D ，Ohlmann P ，Ben Amer H ，Kiss RG ，Ungi I ，Gilard M ... -  《-》

6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial.

The currently recommended duration of dual antiplatelet therapy (DAPT) in drug-eluting stent (DES) recipients is 12 months to reduce the risk of late stent thrombosis, particularly in those with acute coronary syndrome (ACS). This study hypothesized that antiplatelet treatment with DAPT for 6 months may be noninferior to 24-month DAPT in aspirin-sensitive patients. A multicenter, randomized study assigned patients undergoing implantation of everolimus-eluting stents with confirmed nonresistance to aspirin to receive 6- or 24-month DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-stenting. A total of 2,031 patients were enrolled in 70 European and Middle Eastern centers. The trial was prematurely terminated due to recruitment problems, leaving 941 patients randomized to 24-month DAPT and 953 to 6-month DAPT. The 2 treatment groups had similar baseline and procedural characteristics. There was no significant difference in the primary endpoint (24-month: 1.5% vs. 6-month: 1.6%; p = 0.85). Noninferiority was demonstrated for 6- versus 24-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p for noninferiority = 0.0002). There were no significant differences in stent thrombosis or bleeding complications. In the 792 (44%) high-risk patients with ACS, primary and secondary endpoints did not significantly differ (hazard ratio: 1.7 [95% confidence interval: 0.519 to 6.057; p = 0.361]). Rates of bleeding and thrombotic events were not significantly different according to 6- versus 24-month DAPT after PCI with new-generation DES in good aspirin responders. (Is There A LIfe for DES After Discontinuation of Clopidogrel [ITALICplus]; NCT01476020).

Gilard M ，Barragan P ，Noryani AAL ，Noor HA ，Majwal T ，Hovasse T ，Castellant P ，Schneeberger M ，Maillard L ，Bressolette E ，Wojcik J ，Delarche N ，Blanchard D ，Jouve B ，Ormezzano O ，Paganelli F ，Levy G ，Sainsous J ，Carrie D ，Furber A ，Berland J ，Darremont O ，Le Breton H ，Lyuycx-Bore A ，Gommeaux A ，Cassat C ，Kermarrec A ，Cazaux P ，Druelles P ，Dauphin R ，Armengaud J ，Dupouy P ，Champagnac D ，Ohlmann P ，Endresen K ，Benamer H ，Kiss RG ，Ungi I ，Boschat J ，Morice MC ... -  《-》

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227).

Nakamura M ，Iijima R ，Ako J ，Shinke T ，Okada H ，Ito Y ，Ando K ，Anzai H ，Tanaka H ，Ueda Y ，Takiuchi S ，Nishida Y ，Ohira H ，Kawaguchi K ，Kadotani M ，Niinuma H ，Omiya K ，Morita T ，Zen K ，Yasaka Y ，Inoue K ，Ishiwata S ，Ochiai M ，Hamasaki T ，Yokoi H ，NIPPON Investigators ... -  《-》

Adjunctive cilostazol versus double-dose clopidogrel after drug-eluting stent implantation: the HOST-ASSURE randomized trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Safety & Effectiveness of Drug-Eluting Stents & Anti-plate

This study sought to test the noninferiority of triple antiplatelet therapy (TAT) versus double-dose clopidogrel dual antiplatelet therapy (DDAT) in patients undergoing percutaneous coronary intervention (PCI). Antiplatelet regimen is an integral component of medical therapy after PCI. A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI. Yet in Asia, the addition of cilostazol is used more commonly than DDAT in high-risk patients. We randomly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT, which was continued for 1 month, to test the noninferiority of TAT versus DDAT. The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO (Platelet Inhibition and Patient Outcomes) major bleeding. TAT was noninferior to DDAT with respect to the primary outcome, which occurred in 1.2% and 1.4% of patients, respectively (-0.22% absolute difference, 0.34% 1-sided 97.5% confidence interval, p = 0.0007 for noninferiority; hazard ratio: 0.85; 95% confidence interval: 0.49 to 1.48; p = 0.558 for superiority). The individual risks of cardiac death, nonfatal myocardial infarction, stent thrombosis, stroke, and PLATO major bleeding did not differ significantly between the 2 groups. There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome. The adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [HOST-ASSURE]; NCT01267734).

Park KW ，Kang SH ，Park JJ ，Yang HM ，Kang HJ ，Koo BK ，Park BE ，Cha KS ，Rhew JY ，Jeon HK ，Shin ES ，Oh JH ，Jeong MH ，Kim S ，Hwang KK ，Yoon JH ，Lee SY ，Park TH ，Moon KW ，Kwon HM ，Chae IH ，Kim HS ... -  《-》

Duration of dual antiplatelet therapy after implantation of the first-generation and second-generation drug-eluting stents.

Yu X ，Chen F ，He J ，Gao Y ，Wu C ，Luo Y ，Zhang X ，Zhang Y ，Ren X ，Lv S ... -  《-》