Non-Inferiority of Resolute Integrity Drug-Eluting Stent to Benchmark Xience Drug-Eluting Stent.

BACKGROUND: The Resolute Integrity coronary drug-eluting stent (DES), the next evolution of the Resolute DES, is designed with thinner stent struts and continuous sinusoidal technology to further enhance performance. This study evaluated the performance of the Resolute Integrity DES compared with the historical performance of Xience V. Methods and Results: We assessed the safety, efficacy, and deliverability of Resolute Integrity compared with the Xience DES, the prespecified historical control, in PROPEL, a large, real-world prospective, single-arm, open-label study. A total of 1,204 subjects were enrolled in PROPEL and treated with the Resolute Integrity DES at 76 sites in Japan. Lesion and procedural success rates were 100% and 99%, respectively. Patients were equally complex in the Resolute Integrity and Xience cohorts. At 1 year in the clinical-only cohort, the primary endpoint target lesion failure was 4.3% (34/800) in the Resolute Integrity cohort compared with 8.5% (97/1,142) in the Xience historical controls (P<0.001 for non-inferiority). Target vessel failure, major adverse cardiac events, target vessel myocardial infarction, and the composite cardiac death and target vessel myocardial infarction were all lower with Resolute Integrity compared with Xience, including in "high risk" patients. CONCLUSIONS: In the large, prospective, multicenter PROPEL trial, the performance of the Resolute Integrity DES was non-inferior to that of the benchmark Xience DES used as a historical comparator.

Three-Year Clinical Outcome of Patients with Coronary Disease and Increased Event Risk Treated with Newer-Generation Drug-Eluting Stents: From the Randomized DUTCH PEERS Trial.

OBJECTIVE: Limited data is available on the long-term outcome of patients with increased cardiovascular event risk, treated with newer-generation durable polymer drug-eluting stents (DES). METHODS: We therefore assessed 3-year follow-up data of high-risk versus low- to intermediate-risk patients of the randomized DUTCH PEERS trial (NCT01331707). In both risk groups we also compared patients treated with Resolute Integrity versus Promus Element DES. Patients were categorized as "high-risk" if they met ≥1 of the following criteria: (1) diabetes (17.9%); (2) previous myocardial infarction (21.9%); (3) previous coronary revascularization (25.8%); (4) chronic renal failure (3.5%); (5) left ventricular ejection fraction ≤30% (1.5%); and (6) age ≥75 years (17.3%). RESULTS: At the 3-year follow-up, the incidence of the composite endpoint target vessel failure (TVF) (13.2 vs. 7.5%; logrank p < 0.001) and 2 of its components - cardiac death (4.7 vs. 1.5%; logrank p < 0.001) and target vessel revascularization (7.3 vs. 4.7%; logrank p = 0.03) - was higher in high-risk (n = 957) versus low- to intermediate-risk patients (n = 854). Among high-risk patients, treatment with Resolute Integrity (n = 481) and Promus Element stents (n = 476) was similarly safe and efficacious (TVF: 13.3 vs. 13.1%; logrank p = 0.95; definite-or-probable stent thrombosis: 1.7 vs. 1.7%; logrank p = 1.00). CONCLUSIONS: The newer-generation Resolute Integrity and Promus Element stents showed similar results in terms of safety and efficacy for treating high-risk patients, who had significantly higher event rates than patients with low-to-intermediate risk.

Prospective multicentre clinical performance evaluation of second and third generation zotarolimus-eluting stents to treat patients with bifurcated coronary lesions.

AIM: To assess the "real world" clinical outcome of patients with bifurcated lesions undergoing percutaneous coronary intervention with implantation of second and third generations of zotarolimus-eluting stent. METHODS AND RESULTS: Nine Italian centres participated in a prospective multicentre clinical project evaluating the outcome of patients receiving zotarolimus-eluting Resolute stent and Resolute Integrity stents. Patients with bifurcated lesions entered this evaluation. Clinical characteristics and angiographic and procedural details were prospectively recorded. Clinical outcome was prospectively assessed to evaluate the occurrence of major adverse cardiac events (MACE). A total of 577 patients were enrolled. The target lesion was distal left main in 11.1% and left anterior descending artery in 52.8%, and 30.3% of lesions were Medina 1,1,1. At a mean follow-up time of 27.0 ± 13.5 months, the survival free from MACE was 91.8%. Survival free from MACE was similar in patients grouped according to different bifurcated lesion complexity. On the contrary, patients receiving a single stent had better survival free from MACE as compared with those with double stent (P = 0.005). At multivariable analysis, double stenting (but not bifurcated lesion complexity) was found to be a significant predictor of MACE (hazard ratio, 2.52; 95% confidence interval, 1.28-4.94; P = 0.007). Of note, patients receiving the second stent as a bail-out had worse survival free from MACE compared with those who received it as a planned technique (P = 0.045). CONCLUSION: The treatment of patients with bifurcated lesions with second and third generation zotarolimus-eluting stents is associated with good long-term clinical outcomes. Clinical outcome seems to be independent of lesion complexity, but may be influenced by the stenting technique (single or double stenting as well as elective or bail-out double stenting). © 2015 Wiley Periodicals, Inc.

Comparison of the endothelial coverage in everolimus and zotarolimus-eluting stents in normal, atherosclerotic, and bifurcation rabbit iliac arteries.

The aim of this study is to evaluate differences in stent endothelial coverage among the second generation of drug-eluting stents. Incomplete stent coverage is one of the major causes of late stent thrombosis. Rabbits fed a normal diet received an everolimus (Xience Prime; EES) and a zotarolimus-eluting stent (Resolute Integrity; R-ZES) in each iliac artery, followed by sacrifice at 14 and 28 days after stent implantation. In addition, a group of atherosclerotic rabbits similarly received EES and R-ZES, and were sacrificed at 28 days. The extent of stent endothelial coverage was assessed by scanning electron microscopy. To evaluate endothelial coverage after bifurcation stenting, rabbits received EES and R-ZES placed with culotte stenting at the iliac bifurcation, followed by sacrifice at 14 and 28 days. In rabbits fed a normal diet, the percent uncovered strut area 14 days after stent implantation was significantly higher in R-ZES than in EES (10.1% (IQR 9.8-15.5) vs. 3.0% (IQR 1.5-9.7), p = 0.03), whereas it was not significantly different at 28-days (3.9% (IQR 0.8-10.3) vs. 1.0% (IQR 0.0-2.8), p = 0.2). In rabbits with induced atheroma, R-ZES also showed less endothelial coverage 28 days after stent implantation (5.3% (IQR 2.2-9.9) vs. 1.1% (IQR 0-6.2), p = 0.03). In the culotte stenting model, the percent uncovered strut area of the proximal overlapped segment was significantly higher in R-ZES at 14 days (15.8% (IQR 14.3-17.7) vs. 8.8% (IQR 8.3-9.8), p = 0.03) and 28 days (9.9% (IQR 4.1-13.9) vs. 2.5% (IQR 1.6-6.7), p = 0.04) after stent implantation. The carina area also showed a better coverage in EES compared with R-ZES. EES showed a better stent endothelial coverage compared with R-ZES after stent implantation in the early phase in normals, in arteries with lipid rich plaque, and in bifurcation stented sites.

5-Year Outcome Following Randomized Treatment of All-Comers With Zotarolimus-Eluting Resolute Integrity and Everolimus-Eluting PROMUS Element Coronary Stents: Final Report of the DUTCH PEERS (TWENTE II) Trial.

OBJECTIVES: The study sought to evaluate for the first time the 5-year outcomes after treating an all-comers population with newer-generation cobalt chromium-based Resolute Integrity zotarolimus-eluting stents (ZES) (Medtronic, Santa Rosa, California) versus platinum chromium-based PROMUS Element everolimus eluting stents (EES) (Boston Scientific, Natick, Massachusetts). BACKGROUND: The DUTCH PEERS (TWENTE II) (DUrable polymer-based sTent CHallenge of Promus ElemEnt versus ReSolute integrity: TWENTE II) trial is a randomized, multicenter, single-blinded, investigator-initiated all-comers trial that found at its main analysis similar 1-year safety and efficacy for both drug-eluting stents. It is the first randomized trial ever to investigate the Resolute Integrity ZES and the first trial to compare both devices. METHODS: In total, 1,811 patients were 1:1 randomized to ZES versus EES. We performed a pre-specified assessment of the 5-year clinical outcomes in terms of safety and efficacy. The main endpoint target vessel failure (TVF) is a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Secondary endpoints included the individual components of TVF, and stent thrombosis. The study was independently monitored, and adverse clinical events were independently adjudicated. RESULTS: Five-year clinical follow-up data was available in 1,798 (99.3%) patients. The ZES and EES groups showed favorable outcomes, with similar 5-year incidence of TVF (13.2% vs. 14.2%; plog-rank = 0.62) and its individual components: cardiac death (4.5% vs. 4.9%; plog-rank = 0.69), target vessel-related myocardial infarction (3.1% vs. 2.6%; plog-rank = 0.47), and target vessel revascularization (7.6% vs. 8.6%; plog-rank = 0.46). The 5-year incidence of definite or probable stent thrombosis was similar (1.5% vs. 1.3%; plog-rank = 0.83). CONCLUSIONS: At 5-year follow-up, the Resolute Integrity ZES and PROMUS Element EES showed similar and sustained results in terms of safety and efficacy for treating a broad population of all-comers.

Outcome After Myocardial Infarction Treated With Resolute Integrity and Promus Element Stents: Insights From the DUTCH PEERS (TWENTE II) Randomized Trial.

INTRODUCTION AND OBJECTIVES: In acute myocardial infarction (MI), novel highly deliverable drug-eluting stents (DES) may be particularly valuable as their flexible stent designs might reduce device-induced traumas to culprit lesions. The aim of the study was to assess the safety and efficacy of percutaneous coronary interventions with 2 novel durable polymer-coated DES in patients with acute MI. METHODS: The prospective, randomized DUTCH PEERS (TWENTE II) multicenter trial compares Resolute Integrity and Promus Element stents in 1811 all-comer patients, of whom 817 (45.1%) were treated for ST-segment elevation MI or non-ST-segment elevation MI and the 2-year outcome is available in 99.9%. The primary clinical endpoint is target vessel failure (TVF), a composite of cardiac death, target vessel related MI, or target vessel revascularization. RESULTS: Of all 817 patients treated for acute MI, 421 (51.5%) were treated with Resolute Integrity and 396 (48.5%) with Promus Element stents. At the 2-year follow-up, the rates of TVF (7.4% vs 6.1%; P = .45), target lesion revascularization (3.1% vs 2.8%; P = .79), and definite stent thrombosis (1.0% vs 0.5%; P = .69) were low for both stent groups. Consistent with these findings in all patients with acute MI, outcomes for the 2 DES were favorable and similar in both, with 370 patients with ST-segment elevation MI (TVF, 5.1% vs 4.9%; P = .81) and 447 patients with non-ST-segment elevation MI (TVF, 9.0% vs 7.5%; P = .56). CONCLUSIONS: Resolute Integrity and Promus Element stents were both safe and efficacious in treating patients with acute MI. The present 2-year follow-up data underline the safety of using these devices in this particular clinical setting.

Bifurcation treatment with novel, highly flexible drug-eluting coronary stents in all-comers: 2-year outcome in patients of the DUTCH PEERS trial.

BACKGROUND: Percutaneous coronary intervention (PCI) in bifurcated lesions with second-generation drug-eluting stents (DES) was associated with increased myocardial infarction (MI) rates. Flexible stent designs that accommodate well to vessel tapering may be of benefit in challenging anatomies such as bifurcated target lesions, but so far data are scarce. METHODS: We analyzed the 2-year follow-up data of the DUTCH PEERS (TWENTE II) trial, which randomized 1811 all-comer patients to PCI with newer generation resolute integrity zotarolimus-eluting (Medtronic) or promus element everolimus-eluting stents (Boston Scientific). In bifurcated lesions, provisional stenting was generally performed. Target vessel failure is a composite endpoint, consisting of cardiac death, target vessel MI, or target vessel revascularization. RESULTS: Patients with at least one bifurcated lesion (n = 465, 25.7 %) versus patients with non-bifurcated target lesions only (n = 1346, 74.3 %) showed similar rates of clinical endpoints including target vessel failure (9.2 versus 7.9 %, p = 0.36) and definite stent thrombosis (0.4 versus 1.0 %, p = 0.38). Target vessel MI was more common in patients with bifurcated lesions (3.4 versus 1.6 %, p = 0.02); but after multivariate analysis with propensity score adjustment, bifurcation treatment was found not to be an independent predictor of target vessel MI (HR 1.40, 95 % CI 0.71-2.76; p = 0.34). Among patients with bifurcated lesions, DES type and side-branch size did not affect outcome, but periprocedural MI occurred more often after two-stent approaches (9.0 versus 2.1 %; p = 0.002). CONCLUSION: All-comer patients treated for bifurcated and non-bifurcated target lesions showed similar and low rates of clinical endpoints, suggesting that the DES used are efficacious and safe for treating bifurcated target lesions.

Clinical Events and Patient-Reported Chest Pain in All-Comers Treated With Resolute Integrity and Promus Element Stents: 2-Year Follow-Up of the DUTCH PEERS (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial (TWENTE II).

OBJECTIVES: This study assessed clinical events and patient-reported chest pain 2 years after treatment of all-comers with Resolute Integrity zotarolimus-eluting stents (Medtronic Vascular, Santa Rosa, California) and Promus Element everolimus-eluting stents (Boston Scientific, Natick, Massachusetts). BACKGROUND: For both drug-eluting stents (DES), no all-comer outcome data from >12 months of follow-up have been published. Although there is increasing interest in patient-reported chest pain following stenting, data with novel DES are scarce. METHODS: The DUTCH PEERS multicenter trial (TWENTE II) (DUrable Polymer-Based STent CHallenge of Promus ElemEnt Versus ReSolute Integrity) Randomized Trial [TWENTE II]) randomized 1,811 all-comer patients to treatment with 1 type of DES. Monitoring and event adjudication were performed by independent contract research organizations. RESULTS: The 2-year follow-up of 1,810 patients (99.9%) was available. The primary composite endpoint target vessel failure occurred in 8.6% and 7.8% of patients treated with zotarolimus- and everolimus-eluting stents, respectively (p = 0.55). Rates of components of target vessel failure were: cardiac death (2.4% vs. 1.9%, p = 0.42); target vessel-related myocardial infarction (2.4% vs. 1.8%, p = 0.33); clinically-indicated target vessel revascularization (4.6% vs. 4.9%, p = 0.83). At 1- and 2-year follow-up, >80% of patients were free from chest pain (no between-stent difference). In addition, >87% of patients were either free from chest pain or experienced pain only at maximal physical exertion, but not during normal daily activities. Patients with chest pain after 12 months at no more than moderate physical effort had a higher risk of target vessel revascularization during the following year (hazard ratio: 1.89 [95% confidence interval: 1.05 to 3.39], p = 0.03). CONCLUSIONS: During the second year of follow-up, the incidence of adverse clinical endpoints remained similar and low for both DES. The vast majority of patients were free from chest pain.

Deliverability of the Resolute Integrity stent and a post hoc comparison of radial and femoral access: the DELIVER study.

BACKGROUND/PURPOSE: DELIVER (DELiverability of the Resolute Integrity Stent in All-Comer Vessels and Cross-OvER stenting) was a prospective, multicenter, all-comers registry to assess the deliverability of the Resolute Integrity™ zotarolimus-eluting stent (R-ZES). METHODS/MATERIALS: Patients (n=7740 patients, 10449 lesions) undergoing percutaneous coronary intervention and deemed suitable for R-ZES implantation were enrolled and treated according to standard practice of the participating centers in 30 countries. Outcomes included delivery success and in-hospital target lesion failure (TLF), major adverse cardiac event (MACE), and Academic Research Consortium definite/probable stent thrombosis. We performed a post hoc analysis comparing deliverability, in-hospital clinical outcomes and resource utilization with radial vs. femoral access. RESULTS: A high proportion of the population had complex disease (71%): mean lesion length was 26.7±17.5 mm, 35% of lesions were moderately/severely calcified and 17% were bifurcated. Femoral and radial accesses were used in 53% and 46% of patients, respectively. Patients treated using femoral access had more complex coronary artery disease. Primary delivery success was 98.9% and did not differ by approach. Radial access was associated with lower stent and balloon utilization, but higher guide catheter utilization, lower procedure duration, and contrast administered compared with femoral access. In-hospital TLF and MACE occurred in 1.6% of patients; definite or probable stent thrombosis occurred in 0.2%. Clinical outcomes did not differ by vascular access. CONCLUSIONS: R-ZES was found to be highly deliverable in a complex, all-comers, international population, regardless of whether radial or femoral access was used. In-hospital outcomes were excellent with very low risk of complications.