Validation of a simplified intravascular ultrasound core lab analysis method in stented coronary arteries.

OBJECTIVES: To validate a simplified core laboratory intravascular ultrasound (IVUS) analysis method based on frames with visually determined minimal lumen areas (MLAs) as compared with a comprehensive (per frame) analysis method. BACKGROUND: IVUS-guided percutaneous coronary intervention has proven to be superior to angiography-guided stenting. In clinical practice, cross-sections with visually determined MLA are measured to determine lesion severity or minimal stent area (MSA), however, its accuracy has not been compared with a comprehensive per frame analysis method. METHODS: A total of 50 stented coronary segments of anonymized core lab datasets were analyzed using a comprehensive analysis method and reanalyzed by two core lab analysts using the simplified method including a maximum of seven frames to be analyzed (the visually determined MSA, the first and last frame, and the MLA of each reference segment). The main parameters of interest were MSA, MLA in the reference segments, and plaque burden. RESULTS: The simplified method showed moderate agreement for measurement of the proximal MLA (7.51 ± 2.52 vs. 6.32 ± 1.88 mm2 , intraclass correlation coefficient [ICC] = 0.73), good agreement for the distal MLA (5.41 ± 1.85 vs. 5.11 ± 1.38 mm2 , ICC = 0.84) and plaque burden proximal (0.49 ± 0.12 vs. 0.50 ± 0.11, ICC = 0.88), and excellent agreement for the MSA (5.35 ± 1.05 vs. 5.32 ± 0.99 mm2 , ICC = 0.94) and plaque burden distal (0.47 ± 0.14 vs. 0.47 ± 0.12, ICC = 0.92), when compared with the comprehensive analysis method. Inter- and intraobserver analysis revealed good-to-excellent agreement for all parameters. CONCLUSIONS: Measuring poststenting IVUS cross-sections with visually determined MLAs by experienced core lab analysts is an accurate and reproducible method to identify MLAs.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

AIM: To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). METHODS AND RESULTS: Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥ 3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). CONCLUSION: A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial.

AIMS: To compare the long-term clinical safety between two drug-eluting stents with different healing characteristics in the Patient Related Outcomes with Endeavour (E-ZES) vs. Cypher (C-SES) Stenting Trial (PROTECT). At 3 years, there was no difference in the primary outcome of definite or probable stent thrombosis or in the other main secondary clinical outcomes consisting of the composite of death or myocardial infarction (MI). Prespecified 4-year clinical follow-up was analysed. METHODS AND RESULTS: Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial was a prospective, open-label randomized-controlled superiority trial powered to look at differences in long-term clinical safety, including stent thrombosis. Dual antiplatelet therapy (DAPT) was prescribed for ≥ 3 months and up to 12 months based on current guidelines. Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial enrolled 8791 patients undergoing elective or emergency PCI to E-ZES or C-SES. There was no difference in DAPT usage between the two groups up to 4 years. At 4-year follow-up, the primary outcome occurred in 1.6% of E-ZES vs. 2.6% of C-SES patients [HR 0.63 (95% CI 0.46-0.85), P = 0.003]. The composite of all-cause death or large MI occurred in 6.7% of E-ZES vs. 8.0% of C-SES-treated patients [HR 0.84 (95% CI 0.71-0.98), P = 0.024]. CONCLUSIONS: Drug-eluting coronary stents with different healing characteristics demonstrated different late safety profiles: after 4 years, compared with C-SES, E-ZES reduced the risk of stent thrombosis and the risk of the composite endpoints of death or MI. Appropriately powered large-scale trials with long-term follow-up are critical to determine clinical safety and efficacy of permanently implanted coronary stents. This trial is registered with ClinicalTrials.gov, number NCT00476957.

Quality of Life After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting.

BACKGROUND: Differences in quality of life (QoL) after coronary artery bypass grafting (CABG) compared with percutaneous coronary intervention (PCI) are not well characterized. We aimed to compare the short- and long-term effects of CABG versus PCI on QoL. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized controlled trials comparing CABG versus PCI using the Seattle Angina Questionnaire (SAQ)-Angina Frequency, SAQ-QoL, SAQ-Physical Limitations, EuroQoL-5D, and Short-Form Questionnaire. We calculated mean changes within each group from baseline to 1, 6, 12, and 36 to 60 months (latest follow-up) and the weighted mean differences between groups using inverse-variance methods. A total of 10 760 patients were enrolled in 5 trials. From baseline to 12 months and 36 to 60 months, the mean change in SAQ-Angina Frequency was >22 points (95% CI, 21.0-25.6) after both PCI and CABG. The mean difference in SAQ-Angina Frequency was similar between procedures at 1 month and at 36 to 60 months but favored CABG at 12 months (1.97 [95% CI, 0.68-3.26]). SAQ-QoL favored PCI at 1 month (-2.92 [95% CI, -4.66 to -1.18]) and CABG at 6 (2.50 [95% CI, 1.02-3.97]), 12 (3.30 [95% CI, 1.78-4.82]), and 36 to 60 months (3.17 [95% CI, 0.54 5.80). SAQ-Physical Limitations (-12.61 [95% CI, -16.16 to -9.06]) and EuroQoL-5D (-0.07 [95% CI, -0.08 to -0.07) favored PCI at 1 month. Short-Form Questionnaire-Physical Component favored CABG at 12 months (1.18 [95% CI, 0.46-1.90]). CONCLUSIONS: Both PCI and CABG improved long-term disease-specific and generic QoL.

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

BACKGROUND: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. METHODS: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. RESULTS: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). CONCLUSIONS: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

BACKGROUND: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. METHODS: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m2). RESULTS: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. CONCLUSIONS: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Impact of chronic obstructive pulmonary disease and dyspnoea on clinical outcomes in ticagrelor treated patients undergoing percutaneous coronary intervention in the randomized GLOBAL LEADERS trial.

AIMS: To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. METHODS AND RESULTS: This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21-3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58-1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm. CONCLUSION: In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER: NCT01813435.

Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly patients: a pre-specified analysis of the GLOBAL LEADERS trial.

AIMS: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age. METHODS AND RESULTS: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group. CONCLUSIONS: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.

Impact of Periprocedural Myocardial Biomarker Elevation on Mortality Following Elective Percutaneous Coronary Intervention.

OBJECTIVES: This study sought to explore the association between biomarker elevation, with creatine kinase-myocardial band (CK-MB) or cardiac troponin (cTn), following percutaneous coronary intervention (PCI) and mortality in patients undergoing PCI for stable angina with normal baseline values. BACKGROUND: Several studies have shown a strong association between post-PCI CK-MB elevation and subsequent mortality. However, the prognostic significance of troponin elevation following coronary intervention is still debated. METHODS: Patient-level data from 5 contemporary coronary stent trials and 1 large registry were pooled. Mortality of patients with stable angina, with normal baseline biomarkers, was compared between patients with and those without different cutoff values of cTn and CK-MB. RESULTS: A total of 13,452 patients were included in this pooled analysis. The overall percentage of patients with elevated biomarkers following PCI was 23.9% for CK-MB and 68.4% for cTn. In the patient cohort for whom both assays were available (n = 8,859), 2.4% had both CK-MB ≥5 × the upper limit of normal (ULN) and cTn ≥35 × ULN, while 92% had both CK-MB <5 × ULN and cTn <35 × ULN. Among patients with CK-MB ≥5 × ULN (n = 315), 212 (67.3%) also had cTn ≥35 × ULN. Conversely, 390 of patients (64.8%) who had cTn ≥35 × ULN did not have CK-MB ≥5 × ULN. A total of 259 patients (1.9%) died at 1 year; 20 (7.7%) had CK-MB ≥5 × ULN, and 23 (8.8%) had cTn ≥35 × ULN. In the Cox multivariate analysis, in which the CK-MB and cTn ratios post-procedure were forced into the model, age, prior myocardial infarction, lesion complexity, hyperlipidemia, and CK-MB ratio (≥10) post-procedure were associated with increased 1-year mortality. CONCLUSIONS: Following elective PCI in patients in stable condition treated with second-generation drug-eluting stent, CK-MB and cTn elevations remain common. After multivariate adjustment, there was an increased mortality rate with elevation of CK-MB after PCI, whereas cTn elevation was not independently associated with mortality at 1 year.

Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes: A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial.

Importance: The role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. Objective: To evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and Participants: This is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15 991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. Interventions: The experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and Measures: The primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. Results: Of 15 968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P = .07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P = .004). Conclusions and Relevance: Between 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial Registration: ClinicalTrials.gov identifier: NCT01813435.

Patient-oriented composite endpoints and net adverse clinical events with ticagrelor monotherapy following percutaneous coronary intervention: insights from the randomised GLOBAL LEADERS trial.

AIMS: The aim of this study was to evaluate the impact of 23-month ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) on the rates of patient-oriented composite endpoints (POCE) and net adverse clinical events (NACE). METHODS AND RESULTS: The rates of site-reported Academic Research Consortium (ARC)-2 defined POCE (all-cause death, any stroke, any myocardial infarction or any revascularisation) and NACE (POCE or bleeding type 3 or 5 according to the Bleeding ARC [BARC]) were reported up to two years by intention-to-treat principle in the randomised, multicentre, open-label GLOBAL LEADERS study comparing two antiplatelet strategies in 15,991 patients undergoing PCI. The experimental strategy consisted of aspirin with ticagrelor for one month followed by ticagrelor monotherapy for 23 months, whereas the reference treatment consisted of 12-month DAPT followed by 12-month aspirin monotherapy. At two years, POCE occurred in 1,050 (13.2%) patients in the experimental group and in 1,131 (14.2%) in the reference group (HR 0.93, 95% CI: 0.85-1.01, p=0.085). NACE occurred in 1,145 (14.4%) patients in the experimental group and in 1,237 (15.5%) patients in the reference group (HR 0.92, 95% CI: 0.85-1.00, p=0.057). In pre-specified subgroup analyses, no significant treatment-by-subgroup interactions were found for either POCE or NACE at two years. CONCLUSIONS: The experimental treatment strategy of one-month DAPT followed by 23 months of ticagrelor alone did not result in a significant reduction in the rates of site-reported POCE or NACE, when compared to the reference treatment. ClinicalTrials.gov Identifier: NCT01813435.

Detecting Periprocedural Myocardial Infarction in Contemporary Percutaneous Coronary Intervention Trials.

OBJECTIVES: This study sought to investigate the differences in detecting (e.g., triggering) periprocedural myocardial infarction (PMI) among 3 current definitions. BACKGROUND: PMI is a frequent component of primary endpoints in coronary device trials. Identification of all potential suspected events is critical for accurate event ascertainment. Automatic triggers based on study databases prevent underreporting of events. METHODS: We generated automated algorithms to trigger PMI based on each definition and compared results using data from the RESOLUTE all comers trial. RESULTS: The operationalization of current PMI definitions was achieved by defining programmable algorithms used to interrogate the study database. From a total of 636 PMI triggers, we identified 234 for the World Health Organization extended definition, 382 for the Third Universal definition, and 216 for the Society for Cardiovascular Angiography and Interventions definition. Differences among the biomarkers used, different cutoff values, and in the hierarchy among biomarkers within definitions, yielded a different number of triggers, and identified unique triggers for each definition. Only 38 triggers were consistently identified by all definitions. Availability of ECG data, eCRF data on clinical presentation, and the reporting of >2 post-procedural values of the same biomarker influenced considerably the number of PMI triggers identified. CONCLUSIONS: PMI definitions are not interchangeable. The number of triggers identified and consequently the potential number of events varies significantly, highlighting the importance of rigorous methodology when PMI is a component of a powered endpoint. Emphasis on collection of biomarkers, ECG data, and clinical status at baseline may improve the correct identification of PMI triggers.

Frequency of Stent Thrombosis Risk at 5 Years in Women Versus Men With Zotarolimus-Eluting Compared With Sirolimus-Eluting Stent.

The prevalence of factors that are associated with an increased risk of stent thrombosis (ST), including smoking, diabetes mellitus, and small stent size, is different in women and men who underwent percutaneous coronary intervention. Thus, gender may potentially modify the relation between stent type and the incidence of ST during long-term follow-up. We explored the data of Patient Related Outcomes With Endeavor Versus Cypher stenting Trial (PROTECT) to evaluate this hypothesis. PROTECT randomized 2,061 women and 6,648 men who underwent percutaneous coronary intervention for various indications to Endeavor zotarolimus-eluting stenting (E-ZES) or Cypher sirolimus-eluting stenting (C-SES). Dual antiplatelet therapy was prescribed for at least 3 months. Data on study end points were collected until 5 years after randomization, including ST, death, and cardiovascular events. We analyzed end points and treatment effect (E-ZES vs C-SES) in relation to gender. Women were on average 4.7 years older (65.8 vs 61.1), had a higher prevalence of insulin-dependent diabetes mellitus, were less often smokers, and had a shorter total stent length than men. At discharge and throughout follow-up, a slightly lower fraction of women were using dual antiplatelet therapy. During 5-year follow-up, definite or probable ST was observed in 36 women (1.8%) and 152 men (2.4%; log-rank p = 0.15). E-ZES reduced the incidence of ST compared with C-SES in women (hazard ratio 0.58) and men (hazard ratio 0.61), with no evidence of heterogeneity (p = 0.89). In conclusion, in PROTECT, women and men had similar cumulative incidence of ST at 5 years after stent placement. The favorable effect of the study stent E-ZES over C-SES was not modified by gender.

Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial.

OBJECTIVES: This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. BACKGROUND: The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. METHODS: The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. RESULTS: At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). CONCLUSIONS: The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220).

2-year follow-up of a randomized controlled trial of everolimus- and paclitaxel-eluting stents for coronary revascularization in daily practice. COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTÉ stent in all-comers: a randomized open label trial).

OBJECTIVES: The purpose of this study was to compare the safety and efficacy of the Xience V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the Taxus Liberté (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) at 2-year follow-up. BACKGROUND: COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTÉ stent in all-comers: a randomized open label trial) demonstrated a superior clinical outcome of EES over PES at 1 year in all comers. Whether this superiority is maintained after discontinuation, at 12 months, of dual antiplatelet therapy is unclear. METHODS: Patients undergoing percutaneous coronary intervention with limited exclusion criteria were randomly allocated to EES or PES. The 2-year pre-specified endpoints are composites of safety and efficacy and stent thrombosis. RESULTS: Follow-up was completed in 1,795 of 1,800 patients (99.7%). The groups had similar baseline characteristics. At 2 years, significantly fewer EES patients took dual antiplatelet therapy (11.4% vs. 15.4%, p = 0.02). The primary composite of all death, nonfatal myocardial infarction, and target vessel revascularization occurred in 9.0% of EES patients and 13.7% of PES patients (relative risk [RR]: 0.66; 95% confidence interval [CI]: 0.50 to 0.86) driven by a lower rate of myocardial infarction (3.9% vs. 7.5%; RR: 0.52; 95% CI: 0.35 to 0.77) and target vessel revascularization (3.2% vs. 8.0%; RR: 0.41; 95% CI: 0.27 to 0.62), in parallel with a lower rate of definite or probable stent thrombosis (0.9% vs. 3.9%; RR: 0.23; 95% CI: 0.11 to 0.49). Differences significantly increased between 1- and 2-year follow-up for the primary composite endpoint (p = 0.04), target vessel revascularization (p = 0.02), and definite or probable stent thrombosis (p = 0.02). CONCLUSIONS: The substantial clinical benefit of the EES over the PES with regard to measures of both safety and efficacy is maintained at 2 years in real-life practice with an increasing benefit in terms of safety and efficacy between 1 year and 2 years.