Ming Kai Lam

Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial

BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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. FUNDING Boston Scientific, Medtronic.

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.

Comparison of 3 biodegradable polymer and durable polymer-based drug-eluting stents in all-comers (BIO-RESORT): Rationale and study design of the randomized TWENTE III multicenter trial

AIM To evaluate the safety and efficacy of 2 novel drug-eluting stents (DES) with biodegradable polymer-based coatings versus a durable coating DES. METHODS AND RESULTS BIO-RESORT is an investigator-initiated, prospective, patient-blinded, randomized multicenter trial in 3540 Dutch all-comers with various clinical syndromes, requiring percutaneous coronary interventions (PCI) with DES implantation. Randomization (stratified for diabetes mellitus) is being performed in a 1:1:1 ratio between ORSIRO sirolimus-eluting stent with circumferential biodegradable coating, SYNERGY everolimus-eluting stent with abluminal biodegradable coating, and RESOLUTE INTEGRITY zotarolimus-eluting stent with durable coating. The primary endpoint is the incidence of the composite endpoint target vessel failure at 1 year, consisting of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Power calculation assumes a target vessel failure rate of 8.5% with a 3.5% non-inferiority margin, giving the study a power of 85% (α level .025 adjusted for multiple testing). The impact of diabetes mellitus on post-PCI outcome will be evaluated. The first patient was enrolled on December 21, 2012. CONCLUSIONS BIO-RESORT is a large, prospective, randomized, multicenter trial with three arms, comparing two DES with biodegradable coatings versus a reference DES with a durable coating in 3540 all-comers. The trial will provide novel insights into the clinical outcome of modern DES and will address the impact of known and so far undetected diabetes mellitus on post-PCI outcome.

Fractional Flow Reserve and Coronary Bifurcation Anatomy : A Novel Quantitative Model to Assess and Report the Stenosis Severity of Bifurcation Lesions

OBJECTIVES The aim of this study was to develop a new model for assessment of stenosis severity in a bifurcation lesion including its core. The diagnostic performance of this model, powered by 3-dimensional quantitative coronary angiography to predict the functional significance of obstructive bifurcation stenoses, was evaluated using fractional flow reserve (FFR) as the reference standard. BACKGROUND Development of advanced quantitative models might help to establish a relationship between bifurcation anatomy and FFR. METHODS Patients who had undergone coronary angiography and interventions in 5 European cardiology centers were randomly selected and analyzed. Different bifurcation fractal laws, including Murray, Finet, and HK laws, were implemented in the bifurcation model, resulting in different degrees of stenosis severity. RESULTS A total of 78 bifurcation lesions in 73 patients were analyzed. In 51 (65%) bifurcations, FFR was measured in the main vessel. A total of 34 (43.6%) interrogated vessels had an FFR≤0.80. Correlation between FFR and diameter stenosis was poor by conventional straight analysis (ρ=-0.23, p<0.001) but significantly improved by bifurcation analyses: the highest by the HK law (ρ=-0.50, p<0.001), followed by the Finet law (ρ=-0.49, p<0.001), and the Murray law (ρ=-0.41, p<0.001). The area under the receiver-operating characteristics curve for predicting FFR≤0.80 was significantly higher by bifurcation analysis compared with straight analysis: 0.72 (95% confidence interval: 0.61 to 0.82) versus 0.60 (95% confidence interval: 0.49 to 0.71; p=0.001). Applying a threshold of ≥50% diameter stenosis, as assessed by the bifurcation model, to predict FFR≤0.80 resulted in 23 true positives, 27 true negatives, 17 false positives, and 11 false negatives. CONCLUSIONS The new bifurcation model provides a comprehensive assessment of bifurcation anatomy. Compared with straight analysis, identification of lesions with preserved FFR values in obstructive bifurcation stenoses was improved. Nevertheless, accuracy was limited by using solely anatomical parameters.

Clinical outcome of patients with implantation of second‐generation drug‐eluting stents in the right coronary ostium: Insights from 2‐year follow‐up of the TWENTE trial

The aim of the present study was to assess the impact on clinical outcome of right coronary artery (RCA) ostial coverage with second‐generation drug‐eluting stents (DES).

Three-year clinical outcome of patients with bifurcation treatment with second-generation Resolute and Xience V stents in the randomized TWENTE trial

BACKGROUND Only limited data from large randomized clinical trials have been published on the long-term performance of second-generation drug-eluting stents in bifurcation lesions. METHODS We investigated in patients in the randomized TWENTE trial the long-term safety and efficacy of treating bifurcation lesions with 2 widely applied second-generation drug-eluting stents, the zotarolimus-eluting Resolute stent (Medtronic Inc, Santa Rosa, CA) and the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA). Three-year follow-up was available in 99.3%. Patients were categorized into treatment for ≥1 bifurcation lesion versus treatment for nonbifurcation lesions only. RESULTS Among the 1,391 patients of the TWENTE trial, 362 (26%) were treated for bifurcation lesions. At 3-year follow-up, target-vessel failure did not differ between patients treated for bifurcation versus nonbifurcation lesions (13.1% vs 12.6%; P = .84), whereas the periprocedural myocardial infarction rate was higher in patients with bifurcation lesions (6.9% vs 3.1%; P < .01). Of the 362 patients with bifurcation lesion treatment, 179 (49.4%) were treated with Resolute and 183 (50.6%) with Xience V. There was no significant difference in target-vessel failure between the Resolute and Xience V groups with bifurcation treatment (13.6% vs 12.6%; P = .78), and their incidence of definite-or-probable stent thrombosis was low and similar (1.1% vs 0.5%, respectively; P = .62). CONCLUSION Despite a significant difference in periprocedural myocardial infarction, 3-year clinical outcome after implantation of second-generation stents was favorable and similar for patients with and without bifurcation lesions. In addition, we observed no difference in long-term clinical outcome after bifurcation lesion treatment with Resolute and Xience V stents.

Three-year clinical outcome after treatment of chronic total occlusions with second-generation drug-eluting stents in the TWENTE trial

To compare long‐term outcome of patients treated for chronic total occlusion (CTO) lesions versus patients treated for non‐CTO lesions only.

Impact of previous coronary artery bypass surgery on clinical outcome after percutaneous interventions with second generation drug-eluting stents in TWENTE trial and Non-Enrolled TWENTE registry

BACKGROUND Patients with previous coronary artery bypass grafting (CABG) who underwent percutaneous coronary intervention (PCI) have an increased repeat revascularization rate, but data on contemporary second-generation drug-eluting stents (DES) are scarce. METHODS We evaluated 1-year clinical outcome following secondary revascularization by PCI in patients of the TWENTE trial and non-enrolled TWENTE registry, and compared patients with previous CABG versus patients without previous CABG. RESULTS Of all 1709 consecutive patients, 202 (11.8%) had previously undergone CABG (on average 11.2±8.5 years ago). CABG patients were older (68.5±9.4 years vs. 64.1±10.7 years, P<0.001) and more often had diabetes (28.7% vs. 20.9%, P=0.01) and previous PCI (40.1% vs. 19.8%, P<0.001) compared to patients without previous CABG. Nevertheless, a higher target vessel revascularization (TVR) rate following PCI in the CABG patients (9.4% vs. 2.3%, P<0.001) was the only significant difference in clinical outcome at 1-year follow-up (available for 99.6%). Among CABG patients, the TVR rate was significantly higher in patients treated for graft lesions (n=65; 95.4% in vein grafts) than in patients treated for native coronary lesions only (n=137) (18.5% vs. 5.1%, P=0.002). Among 1638 patients with PCI of native coronary lesions only, there was only a non-significant difference in TVR between patients with previous CABG versus patients without previous CABG (5.1% vs. 2.3%, P=0.08). CONCLUSIONS Patients with previous CABG showed a favorable safety profile after PCI with second-generation DES. Nevertheless, their TVR rate was still much higher, driven by more repeat revascularizations after PCI of degenerated vein grafts. In native coronary lesions, there was no such difference.

Complex patients treated with zotarolimus-eluting resolute and everolimus-eluting xience V stents in the randomized TWENTE trial : Comparison of 2-year clinical outcome

To assess the differences in clinical outcome between complex patients treated with Resolute zotarolimus‐eluting stents (ZES) versus Xience V everolimus‐eluting stents (EES).

Coronary Bifurcations: Still the Touchstone of Drug-eluting Stents and Bioresorbable Vascular Scaffolds?

Coronary bifurcation lesions that involve significant side branches represent a particularly challenging subset of target lesions for percutaneous coronary interventions. Besides the necessity for the interventional cardiologist to often perform technically demanding interventions with more procedural steps, clinical outcome following percutaneous coronary intervention has usually been somewhat inferior. For more than two decades, coronary bifurcation lesions represent a serious touchstone for both interventional cardiologists and various types of stents and vascular scaffolds. The use of first-generation drug-eluting stents (DES) has reduced the incidence of restenosis following percutaneous coronary intervention of bifurcation lesions as compared to bare metal stents. In a first, small-sized study by Colombo et al, a numerically lower rate of angiographic restenosis was seen in bifurcated lesions treated with a single DES in the main vessel. In the meantime, pooled data of the Nordic Bifurcation and the British Bifurcation Coronary studies, both using first-generation Cypher DES (Cordis; Waaren, New Jersey, United States), have clearly demonstrated at 9-month follow-up that clinical outcome is superior following a simple approach with provisional Tstenting of the side branch vs a complex approach. In addition, the Nordic Bifurcation study has shown that long-term outcome (up to 5 years) following bifurcation stenting with a simple approach was at least as good as the outcome of a complex approach. The aforementioned studies were performed with the first-generation Cypher stent that had a closed-cell design. The results of several in vitro studies and bench tests suggest that DES with different stent materials and designs may act differently in the setting of bifurcation stenting. Moreover, the coatings of various DES types show significant dissimilarities in mechanical properties, which may be relevant during kissing balloon inflations that apply a significant shear stress to the coatings of DES. Consequently, the assessment of clinical outcome