Benefits and Risks of Extended Dual Antiplatelet Therapy After Everolimus-Eluting Stents.

The purpose of this study was to characterize outcomes for everolimus-eluting stent (EES)-treated subjects according to treatment with continued thienopyridine plus aspirin versus aspirin alone 12 to 30 months after stenting. In the DAPT (Dual Antiplatelet Therapy) study, continued thienopyridine plus aspirin beyond 1 year after coronary stenting reduced ischemic events. Given low rates of stent thrombosis and myocardial infarction (MI) for current drug-eluting stents, we examined outcomes among EES-treated subjects in the DAPT study. The DAPT study enrolled 25,682 subjects (11,308 EES-treated) after coronary stenting. Following 12 months of treatment with thienopyridine and aspirin, eligible subjects continued treatment with aspirin and 9,961 (4,703 with EES) were randomized to 18 months of continued thienopyridine or placebo. Stent type was not randomized, and the EES subset analysis was post hoc. Among EES-treated patients, continued thienopyridine reduced stent thrombosis (0.3% vs. 0.7%, hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.15 to 0.97; p = 0.04) and MI (2.1% vs. 3.2%, HR: 0.63, 95% CI: 0.44 to 0.91; p = 0.01) versus placebo but did not reduce a composite of death, MI, and stroke (4.3% vs. 4.5%, HR: 0.89, 95% CI: 0.67 to 1.18; p = 0.42), and increased moderate/severe bleeding (2.5% vs. 1.3%, HR: 1.79, 95% CI: 1.15 to 2.80; p = 0.01), and death (2.2% vs. 1.1%, HR: 1.80, 95% CI: 1.11 to 2.92; p = 0.02). Death due to cancer and not related to bleeding was increased (0.64% vs. 0.17%; p = 0.01). In EES-treated subjects, significant reductions in stent thrombosis and MI and an increase in bleeding were observed with continued thienopyridine beyond 1 year compared with aspirin alone. (The Dual Antiplatelet Therapy Study [DAPT Study]); NCT00977938).

Hermiller JB ，Krucoff MW ，Kereiakes DJ ，Windecker S ，Steg PG ，Yeh RW ，Cohen DJ ，Cutlip DE ，Massaro JM ，Hsieh WH ，Mauri L ，DAPT Study Investigators ... -  《-》

Myocardial Infarction Risk After Discontinuation of Thienopyridine Therapy in the Randomized DAPT Study (Dual Antiplatelet Therapy).

Thienopyridine plus aspirin beyond 1 year after coronary stenting reduces myocardial infarction (MI) risk and increases bleeding risk in comparison with aspirin alone. The hazard associated with late thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined. In the DAPT Study (Dual Antiplatelet Therapy), after percutaneous coronary intervention and 12 months of thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomly assigned to continued thienopyridine versus placebo for 18 months. At 30 months, patients stopped the study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT score values <2 or ≥2. Among the 11 648 randomly assigned patients, the monthly cumulative incidence of MI was lower with continued thienopyridine versus placebo at 12 to 15 months (0.12% versus 0.37%, P<0.001, in all patients; 0.13% versus 0.27%, P=0.02, in patients not treated with paclitaxel-eluting stents), and higher at 30 to 33 months (0.30% versus 0.15%, P=0.013, in all patients; in patients without paclitaxel-eluting stents, 0.18% versus 0.17%, P=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis. After multivariable adjustment, treatment arm independently predicted MI at months 12 to 15 (P<0.001) and 30 to 33 (P=0.011). During months 12 to 15, patients with DAPT scores <2 or ≥2 both had lower rates of MI with continued thienopyridine (MI monthly incidence 0.16% versus 0.51%, P<0.001, for scores ≥2; 0.08% versus 0.24%, P=0.012, for scores<2, interaction P=0.064). Discontinuing thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to stent thrombosis; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with paclitaxel-eluting stents. Although higher DAPT scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Stefanescu Schmidt AC ，Kereiakes DJ ，Cutlip DE ，Yeh RW ，D'Agostino RB Sr ，Massaro JM ，Hsieh WH ，Mauri L ，DAPT Investigators ... -  《-》

Extended Duration Dual Antiplatelet Therapy After Coronary Stenting Among Patients With Peripheral Arterial Disease: A Subanalysis of the Dual Antiplatelet Therapy Study.

This study sought to determine whether patients with peripheral arterial disease (PAD) experience different reductions in ischemic event and increases in bleeding events with extended duration dual antiplatelet therapy versus those without PAD. Patients with PAD have increased ischemic and bleeding risks after coronary stenting. The DAPT (Dual Antiplatelet Therapy) study randomized 11,648 patients free from ischemic and bleeding events 12 months after coronary stenting to continued thienopyridine plus aspirin therapy for an additional 18 months versus aspirin therapy alone. The effects of continued thienopyridine on myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (death, MI, or stroke) and bleeding (GUSTO [Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries] moderate or severe) were assessed among those with versus without PAD. Among 11,648 randomized patients, 649 (5.57%) had PAD. Between 12 and 30 months, randomized patients with PAD had higher rates of MI/stent thrombosis (6.03% vs. 2.92%; p < 0.001), major adverse cardiovascular and cerebrovascular events (11.65% vs. 4.62%; p < 0.001), and bleeding (4.86% vs. 1.74%; p < 0.001). Continued thienopyridine versus placebo was associated with consistent treatment effects for MI/stent thrombosis (with PAD, HR: 0.63; 95% CI: 0.32 to 1.22; without PAD, HR: 0.53; 95% CI: 0.42, 0.66; interaction p = 0.631), major adverse cardiovascular and cerebrovascular events (with PAD, HR: 1.06; 95% CI: 0.67 to 1.67; without PAD, HR: 0.70; 95% CI: 0.59 to 0.84; interaction p = 0.103), and bleeding (with PAD, HR, 1.82; 95% CI: 0.87 to 3.83; without PAD, HR: 1.66; 95% CI: 1.23 to 2.24; interaction p = 0.811). Among patients undergoing coronary stenting, those with PAD have more ischemic and bleeding events versus those without PAD. Extended duration dual antiplatelet therapy is associated with consistent ischemic benefit and bleeding harm among patients with and without PAD.

Secemsky EA ，Yeh RW ，Kereiakes DJ ，Cutlip DE ，Steg PG ，Massaro JM ，Apruzzese PK ，Mauri L ，Dual Antiplatelet Therapy Study Investigators ... -  《-》

Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy.

This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS. Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES. Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months. Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p < 0.001). DES-treated subjects have long-term rates of stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938).

Kereiakes DJ ，Yeh RW ，Massaro JM ，Driscoll-Shempp P ，Cutlip DE ，Steg PG ，Gershlick AH ，Darius H ，Meredith IT ，Ormiston J ，Tanguay JF ，Windecker S ，Garratt KN ，Kandzari DE ，Lee DP ，Simon DI ，Iancu AC ，Trebacz J ，Mauri L ，DAPT Study Investigators ... -  《-》

6-Month Versus 12-Month Dual-Antiplatelet Therapy Following Long Everolimus-Eluting Stent Implantation: The IVUS-XPL Randomized Clinical Trial.

The aim of this study was to investigate whether a 6-month dual-antiplatelet therapy (DAPT) duration was comparable with a 12-month duration in patients who underwent everolimus-eluting stent implantation. Well-designed studies that determine optimal DAPT strategies after everolimus-eluting stent implantation are limited. A total of 1,400 patients (implanted mean total stent length >45 mm) were randomly assigned to receive 6-month (n = 699) or 12-month (n = 701) DAPT between October 2010 and July 2014 at 20 centers in Korea. The primary endpoint was the composite of cardiac death, myocardial infarction, stroke, or TIMI (Thrombolysis in Myocardial Infarction) major bleeding at 1 year, analyzed using an intention-to-treat approach. The primary endpoint occurred in 15 patients (2.2%) in the 6-month DAPT group and 14 patients (2.1%) in the 12-month DAPT group (hazard ratio [HR]: 1.07; p = 0.854). Definite or probable stent thrombosis occurred in 2 patients (0.3%) in the 6-month DAPT group and in 2 patients (0.3%) in the 12-month DAPT group (HR: 1.00; p = 0.999). There were no significant between-group differences in the primary endpoint in 686 patients with acute coronary syndrome (2.4% in both groups; HR: 1.00; p = 0.994) and in 506 patients with diabetes mellitus (2.2% [6-month] vs. 3.3% [12-month]; HR: 0.64; p = 0.428). Compared with 12-month DAPT, 6-month DAPT did not increase the composite events of cardiac death, myocardial infarction, stroke, or TIMI major bleeding at 1 year in patients who underwent everolimus-eluting stent implantation. (Impact of Intravascular Ultrasound Guidance on Outcomes of XIENCE PRIME Stents in Long Lesions [IVUS-XPL Study]; NCT01308281).

Hong SJ ，Shin DH ，Kim JS ，Kim BK ，Ko YG ，Choi D ，Her AY ，Kim YH ，Jang Y ，Hong MK ，IVUS-XPL Investigators ... -  《-》