zotarolimus and Death--Sudden--Cardiac

The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown.. The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT.. In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. ClinicalTrials.gov Identifiers: NCT00617084; NCT00726453; NCT00752128; NCT00927940.

Topics: Aspirin; Blood Vessel Prosthesis; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Failure; Sirolimus; Ticlopidine; Time Factors; Treatment Outcome; Withholding Treatment

The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been established yet. The objectives of this study were to evaluate the optimal duration of DAPT after the DES implantation.. From three randomized controlled trials investigating DAPT duration after coronary stent implantation, we evaluated the clinical outcomes of short-term (6 months or less) DAPT compared with prolonged DAPT (12 months or more) in 1661 DES-treated pairs matched by propensity scores. At follow-up of 1 year, net adverse clinical event (NACE) was defined as cardiac death, myocardial infarction, target vessel revascularization, definite/probable stent thrombosis, or thrombolysis in myocardial infarction major bleeding.. Short-term DAPT as compared with prolonged DAPT was not associated with 1-year NACEs after DES implantation [hazard ratio (HR) 1.068, 95 % confidence interval (CI) 0.787-1.450, p = 0.671]. Predictors for NACEs were old age (>75 years), hypertension, diabetes mellitus, renal dysfunction (serum creatinine ≥2.0 mg/dL), and multi-vessel disease. The DAPT strategy differentially contributed to the occurrence of NACEs according to the risk burden (p for interaction <0.001). In patients with low risk for NACEs, bleeding events were less in short-term DAPT than in prolonged DAPT (HR 0.332, 95 % CI 0.130-0.849, p = 0.021) (p for interaction = 0.098). Meanwhile, short-term DAPT was associated with more ischemic events that included cardiac death, myocardial infarction, target vessel revascularization, or definite/probable stent thrombosis (HR 2.164, 95 % CI 1.340-3.494, p = 0.002) (p for interaction <0.001) in patients with high risk for NACEs.. One-year clinical outcomes of DAPT after DES implantation depended on the burden of cardiovascular risk.

Topics: Aged; Aspirin; Clopidogrel; Coronary Artery Disease; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Republic of Korea; Risk Factors; Sirolimus; Ticlopidine; Time Factors

Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial.. In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707.. Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned study treatment (six [1%] in the zotarolimus-eluting stent group vs five [1%] in the everolimus-eluting stent group; p=0·22). 12-month follow-up results were available for 1810 patients (one patient in the zotarolimus-eluting stent group withdrew consent). The primary endpoint was met by 55 (6%) of 905 patients in the zotarolimus-eluting stent group and 47 (5%) of 905 in the everolimus-eluting stent group. The zotarolimus-eluting stent was non-inferior to the everolimus-eluting stent (absolute risk difference 0·88%, 95% CI -1·24% to 3·01%; upper limit of one-sided 95% CI 2·69%; non-inferiority p=0·006). We noted no significant between-group differences in individual components of the primary endpoint. Definite stent thrombosis occurred in three (0·3%) patients in the zotarolimus-eluting stent group and six (0·7%) patients in the everolimus-eluting stent group (p=0·34). Longitudinal stent deformation was seen only in the everolimus-eluting stent group (nine [1·0%] of 905 vs 0 of 906, p=0·002; nine of 1591 [0·6%] everolimus-eluting stents implanted became deformed), but was not associated with any adverse events.. Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions.. Boston Scientific, Medtronic.

Topics: Adult; Aged; Aged, 80 and over; Coronary Occlusion; Death, Sudden, Cardiac; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Single-Blind Method; Sirolimus; Treatment Outcome; Young Adult

In the RESOLUTE All Comers trial, the Resolute zotarolimus-eluting stent was non-inferior to the Xience V everolimus-eluting stent for the primary stent-related endpoint of target lesion failure (cardiac death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation) at 1 year. However, data for long-term safety and efficacy from randomised studies of new generation drug-eluting coronary stents in patients treated in routine clinical practice are scarce. We report the prespecified 2-year clinical outcomes from the RESOLUTE All Comers trial.. In 2008, patients with at least one coronary lesion 2.25-4.0 mm in diameter, with greater than 50% stenosis, were randomly assigned to a Resolute zotarolimus-eluting stent or a Xience V everolimus-eluting stent at 17 centres in Europe and Israel. Randomisation was by an interactive voice response system stratified by centre. Study investigators were not masked to treatment allocation; but those who did data management and analysis, and patients were masked. There were no restrictions as to the number of vessels or lesions treated, or the number of stents implanted. We assessed prespecified safety and efficacy outcomes at 2 years with specific focus on patient-related composite (all death, all myocardial infarction, all revascularisation) and stent-related composite outcomes. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00617084.. 1140 patients were assigned to the zotarolimus-eluting stent and 1152 to the everolimus-eluting stent; 1121 and 1128 patients, respectively, completed 2-year follow-up. The patient-related outcome (231 [20.6%] zotarolimus vs 231 [20.5%] everolimus; difference 0.1%, 95% CI-3.2 to 3.5; p=0.958) and stent-related outcome (126 [11.2%] vs 121 [10.7%]; difference 0.5%, -2.1 to 3.1; p=0.736) did not differ between groups, although rates of the stent-related outcome were substantially lower than were those for the patient-related outcome. Three patients in each group (0.3%) had very late (after 1 year) stent thrombosis.. Similar safety and efficacy outcomes were sustained between two new generation drug-eluting stents at 2-year follow-up. The greater number of patient-related than stent-related events in patients with complex clinical and lesion characteristics emphasises that during long-term follow-up, the optimisation of secondary prevention is at least as important as the selection of which new generation drug-eluting stent to implant in a specific lesion.. Medtronic (USA).

Topics: Adult; Aged; Confounding Factors, Epidemiologic; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Europe; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Israel; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Prospective Studies; Secondary Prevention; Sirolimus; Treatment Outcome

We compared safety and efficacy outcomes of 3 limus-based drug-eluting stents in the 'all-comers' PROENCY (PROmus/ENdeavor/CYpher) registry.. Limited data are available on head-to-head comparisons of the everolimus-eluting stent (EES) with the zotarolimus-eluting stent (ZES) or the sirolimus- eluting stent (SES) in the treatment of patients with coronary artery disease.. PROENCY was a prospective, open-label, multicenter, observational study including consecutive patients undergoing planned treatment with EES, ZES, or SES. Seventeen centers were designated to place an EES or SES, 14 other centers were designated to place EES or ZES. The primary endpoint was the composite of cardiac death, myocardial infarction, and target vessel revascularization (TVR) at 12 months. Unadjusted and propensity-adjusted outcomes were compared between groups.. A total of 1921 patients were enrolled in the study from February to December 2008, of which 1704 patients received only study stents and were analyzed. At 12 months, the unadjusted major adverse event rate was significantly lower in the EES group versus the ZES group (3.1% vs 8.7%; P=.001) and the SES group (5.2% vs 9.6%; P=.01). This was mainly driven by lower TVR rates [2.6% with EES vs 8.2% with ZES [P<.001] and 4.1% with EES vs 7.0% with SES [P=.05]. Stent thrombosis rates were low and comparable. Adjusted analyses confirmed the unadjusted results.. There were no differences in safety outcomes of EES, ZES, and SES at 12 months in PROENCY. However, differences in efficacy were observed between the 3 "limus"-based stents in a real-world patient population.

Topics: Aged; Coronary Artery Disease; Death, Sudden, Cardiac; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; France; Germany; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Prospective Studies; Registries; Sirolimus; Thrombosis; Treatment Outcome

Topics: Coronary Angiography; Coronary Restenosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Revascularization; Randomized Controlled Trials as Topic; Secondary Prevention; Sirolimus; Treatment Outcome

Zotarolimus-eluting stents (ZESs) have been shown to be safe and effective in randomised trials. We sought to report the clinical outcomes after implantation of ZES in real-world clinical practice.. ZES have been approved for clinical use in Singapore since April 2005. Until December 31, 2007, a total of 219 patients had undergone implantation of ZES. After excluding 11 foreign patients with whom contact was lost, 208 patients (246 lesions, 305 stents) formed the study cohort. A high-proportion of diabetic patients (n=90, 43.3%) was included. Recommended dual antiplatelet therapy was at least 3 months (n=147) for patients treated before or 12 months (n=61) after January 2007. As of January 2008, the median follow-up duration was 19 months (range: 1 to 33 months). There were 10 (4.8%) deaths, including 7 (3.4%) cardiac deaths. Myocardial infarction occurred in 11 (5.3%) patients. The numbers of patients requiring target vessel revascularisation and target lesion revascularisation were 10 (4.8%) and 5 (2.4%) respectively. Using the ARC definition, there were two cases of definite stent thrombosis on days 7 and 17, and one case of probable stent thrombosis on day 15.. In this real-world clinical experience, ZES was associated with a low incidence of adverse cardiac events at a medium follow-up of one and half years.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Death, Sudden, Cardiac; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Inpatients; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Retrospective Studies; Sirolimus