sirolimus and thienopyridine

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point.

Topics: Aged; Aspirin; Coronary Artery Disease; Coronary Vessels; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Retrospective Studies; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Resistance

Stent fracture (SF) and peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation are considered to be related to very late stent thrombosis (VLST). How dual antiplatelet therapy (DAPT) beyond 1 year affects the clinical outcomes of patients with SF or PSS remains unclear.Methods and Results:Based on their DAPT status, 1,962 patients undergoing SES implantation were classified as on-thienopyridine (n=1,404) or off-thienopyridine (n=558). The 6-year incidence of VLST was significantly lower in the on-thienopyridine patients (0.56% vs. 1.8%, P=0.01), whereas cardiac death and myocardial infarction (MI) were similar (5.0% vs. 6.2%, P=0.31; 3.2% vs. 4.0%, P=0.33; respectively). The 1,962 patients were also classified as having SF/PSS (n=256) or non-SF/PSS (n=1,706). In the SF/PSS group, VLST and MI were significantly lower in on-thienopyridine patients (1.9% vs. 10.1%, P=0.003; 3.5% vs. 10.3%, P=0.02; respectively). In the non-SF/PSS group, VLST and MI were similar (0.36% vs. 0.45%, P=0.78; 3.2% vs. 3.0%, P=0.93; respectively). In both groups, cardiac death was similar (3.6% vs. 4.3%, P=0.78; 5.2% vs. 6.5%, P=0.32; respectively).. Prolonged DAPT was associated with significantly lower incidences of VLST and MI in the SF/PSS group, but had no effect on cardiac death, VLST, or MI in the non-SF/PSS group.

Topics: Aged; Aspirin; Death; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prosthesis Implantation; Pyridines; Retrospective Studies; Sirolimus; Staining and Labeling; Thrombosis; Time Factors; Treatment Outcome

To investigate the risks and benefits of prolonged dual antiplatelet therapy (DAPT: thienopyridine plus aspirin) following placement of drug-eluting stents (DES). The optimal duration of DAPT is not well established.. We analyzed a prospective registry of 2,050 patients with sirolimus-eluting stents during a 5-year follow-up. We divided 1,691 patients into two groups according to DAPT duration (DAPT ≤12 months (n=749) and DAPT >12 months (n=942)) and compared the clinical outcomes using a landmark analysis.. The frequencies of major adverse cardiac events (MACE: 15.6% vs. 18.2%), death (10.0% vs. 11.5%), myocardial infarction (2.3% vs. 2.1%), target lesion revascularization (4.5% vs. 6.3%) and stent thrombosis (0.8% vs. 0.8%) were similar between the two groups. However, the frequency of bleeding was higher in the DAPT >12 months group (1.1% vs. 2.6%, p=0.030). The adjusted 12-month landmark analysis showed no differences in the incidence of MACE (hazard ratio (HR) 0.892; 95% confidence interval (CI) 0.689-1.155; p=0.385) or a composite of target vessel revascularization, cardiac death and myocardial infarction (target vessel failure: HR 0.922; 95% CI 0.678-1.255; p=0.606). There were no differences in the frequency of stent thrombosis between the two groups during years 2 to 5 after stenting; however, with regard to bleeding, an increase in the frequency of hemorrhage events was observed after four years from the index procedures in the DAPT >12 months group.. DAPT performed beyond 12 months is associated with increased an frequency of bleeding complications and does not prevent the incidence of MACE, including stent thrombosis, during five years of follow-up after sirolimus-eluting stent implantation. Conducting larger, randomized studies will therefore be needed to confirm this finding.

Topics: Aged; Asian People; Aspirin; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Population Surveillance; Prospective Studies; Pyridines; Retrospective Studies; Sirolimus; Time Factors; Treatment Outcome

Due to serious concerns on very late stent thrombosis (VLST), extended use of dual antiplatelet therapy (DAPT) beyond 1 year after DES implantation has become a common clinical practice despite apparent lack of evidence suggesting its efficacy in reducing VLST. The study population consisted of 12812 patients in the j-Cypher registry who were treated with at least one sirolimus-eluting stent (SES). We assessed the relation between duration of thienopyridine therapy and clinical outcomes with a landmark analysis at 1 year after SES implantation. Among 11713 patients without myocardial infarction (MI), stent thrombosis and stroke at 1 year who were eligible for the landmark analysis, 7414 patients (63 %) were maintained on thienopyridine at 1-year landmark point, while 4299 patients (37 %) had discontinued thienopyridine before 1-year landmark point. Patients in the on-thienopyridine group had more complex characteristics than patients in the off-thienopyridine group. Cumulative incidence of and the risk for definite VLST in the on-thienopyridine group relative to the off-thienopyridine group favored prolonged DAPT, but were not significant [0.9 and 1.2 %, P = 0.1, and adjusted HR (95 % CI): 0.71 (0.47-1.06), P = 0.11]. Cumulative incidence of and the risk for a composite of death, MI, or stroke in the on-thienopyridine group relative to the off-thienopyridine group were also not significant [15.3 and 14.3 %, P = 0.15, and adjusted HR (95 % CI): 0.99 (0.89-1.11), P = 0.89]. Prolonged use of thienopyridine beyond 1 year after SES implantation was not associated with significant decrease in the risks for VLST or for serious cardiovascular events including death, MI or stroke.

Topics: Aged; Aged, 80 and over; Coronary Artery Disease; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Pyridines; Registries; Sirolimus; Thrombosis; Treatment Outcome

The influences of antiplatelet therapy discontinuation on the risk of stent thrombosis and long-term clinical outcomes after drug-eluting stent implantation have not yet been addressed adequately.. In an observational study in Japan, 2-year outcomes were assessed in 10 778 patients undergoing sirolimus-eluting stent implantation. Data on status of antiplatelet therapy during follow-up were collected prospectively. Incidences of definite stent thrombosis were 0.34% at 30 days, 0.54% at 1 year, and 0.77% at 2 years. Thienopyridine use was maintained in 97%, 62%, and 50% of patients at 30 days, 1 year, and 2 years, respectively. Patients who discontinued both thienopyridine and aspirin had a significantly higher rate of stent thrombosis than those who continued both in the intervals of 31 to 180 days, 181 to 365 days, and 366 to 548 days after stent implantation (1.76% versus 0.1%, P<0.001; 0.72% versus 0.07%, P=0.02; and 2.1% versus 0.14%, P=0.004, respectively). When discontinuation of aspirin was taken into account, patients who discontinued thienopyridine only did not have an excess of stent thrombosis in any of the time intervals studied. Adjusted rates of death or myocardial infarction at 24 months were 4.1% for patients taking thienopyridine and 4.1% for patients not taking thienopyridine (P=0.99) in the 6-month landmark analysis.. Discontinuation of both thienopyridine and aspirin, but not discontinuation of thienopyridine therapy only, was associated with an increased risk of stent thrombosis. Landmark analysis did not suggest an apparent clinical benefit of thienopyridine use beyond 6 months after sirolimus-eluting stent implantation.

Topics: Aged; Aged, 80 and over; Drug-Eluting Stents; Electrocardiography; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyridines; Sirolimus; Thrombosis

Prolonged periods of dual antiplatelet therapy (DAT), i.e., aspirin plus a thienopyridine, are currently recommended to prevent late drug-eluting stent (DES) thrombosis. The aim of our study was to determine the risk and predictors of bleeding and compliance associated with such prolongation of DAT. In this observational study we examined 2,355 consecutive patients undergoing successful DES implantation at 4 hospitals in Italy from June 2002 to December 2004. Bleeding events occurring on DAT and warfarin or in the first 30 days after stent implantation were excluded. Median duration of DAT was 209 days (interquartile range 178 to 444) and only 158 patients (6.7%) prematurely discontinued DAT. The overall bleeding rate was 1.9% (45), with major bleeding in 19 (0.8%) and minor bleeding in 26 (1.1%). Independent predictors of bleeding were DAT (hazard ratio 19.8, 95% confidence interval [CI] 3.69 to 106.34, p <0.001) and age >65 years (hazard ratio 2.15, 95% CI 1.16 to 4.00, p = 0.02). In patients on DAT, the incidence rate (30 days to 18 months) of any bleeding event was 2.57 per 100 person-years (95% CI 1.85 to 3.48) and major bleeding was 1.10 per 100 person-years (95% CI 0.65 to 1.74). In conclusion, DAT after DES implantation is well tolerated and associated with a very low risk of major bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Confidence Intervals; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Immunosuppressive Agents; Incidence; Italy; Male; Middle Aged; Myocardial Infarction; Patient Compliance; Platelet Aggregation Inhibitors; Prospective Studies; Pyridines; Risk Factors; Sirolimus; Time Factors

Significant advances in interventional cardiology have occurred over the past 30 years, leading to substantial increases in the number and anatomic complexity of treated patients, the long-term success of these procedures, and a reduction in the need for coronary bypass surgery. While the risk ofrestenosis has been dramatically reduced by drug-eluting stents, delayed neo-intimal healing has led to a small, but significant occurrence of "late" stent thrombosis. This thrombotic risk is substantially reduced by continuation of dual-anti-platelet therapy for one or more years following DES placement. Current guidelines for patient selection for DES, for duration of DAT following DES, and for facing surgical and invasive procedures after DES were discussed, and the avoidance of early discontinuation of anti-platelet therapy following DES was emphasized.

Topics: Angioplasty, Balloon, Coronary; Antineoplastic Agents, Phytogenic; Aspirin; Consensus; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Paclitaxel; Platelet Aggregation Inhibitors; Pyridines; Sirolimus

The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents.. A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; P<0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; P=0.92).. Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months.

Topics: Aged; Aspirin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Paclitaxel; Platelet Aggregation Inhibitors; Pyridines; Sirolimus; Stents; Thrombosis; Treatment Outcome

Topics: Algorithms; Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Incidence; Paclitaxel; Platelet Aggregation Inhibitors; Pyridines; Sirolimus; Stents; Survivors; Thrombosis; Ticlopidine

Although drug-eluting stents (DES) significantly reduce restenosis, they require 3 to 6 months of thienopyridine therapy to prevent stent thrombosis. The rate and consequences of prematurely discontinuing thienopyridine therapy after DES placement for acute myocardial infarction (MI) are unknown.. We used prospectively collected data from a 19-center study of MI patients to examine the prevalence and predictors of thienopyridine discontinuation 30 days after DES treatment. We then compared the mortality and cardiac hospitalization rates for the next 11 months between those who stopped and those who continued thienopyridine therapy. Among 500 DES-treated MI patients who were discharged on thienopyridine therapy, 68 (13.6%) stopped therapy within 30 days. Those who stopped were older, less likely to have completed high school or be married, more likely to avoid health care because of cost, and more likely to have had preexisting cardiovascular disease or anemia at presentation. They were also less likely to have received discharge instructions about their medications or a cardiac rehabilitation referral. Patients who stopped thienopyridine therapy by 30 days were more likely to die during the next 11 months (7.5% versus 0.7%, P<0.0001; adjusted hazard ratio=9.0; 95% confidence interval=1.3 to 60.6) and to be rehospitalized (23% versus 14%, P=0.08; adjusted hazard ratio=1.5; 95% confidence interval=0.78 to 3.0).. Almost 1 in 7 MI patients who received a DES were no longer taking thienopyridines by 30 days. Prematurely stopping thienopyridine therapy was strongly associated with subsequent mortality. Strategies to improve the use of thienopyridines are needed to optimize the outcomes of MI patients treated with DES.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cause of Death; Clopidogrel; Combined Modality Therapy; Coronary Restenosis; Drug Administration Schedule; Drug Implants; Female; Follow-Up Studies; Hospitalization; Humans; Life Tables; Male; Middle Aged; Mortality; Myocardial Infarction; Patient Education as Topic; Platelet Aggregation Inhibitors; Prevalence; Proportional Hazards Models; Prospective Studies; Pyridines; Registries; Sirolimus; Stents; Survival Analysis; Thrombosis; Ticlopidine; Treatment Outcome; Treatment Refusal