A Real All-Comers Randomized Trial Comparing Xience Prime and Promus Element Stents

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Abstract: Background. The cobalt chromium everolimus-eluting stent (CoCr-EES) has shown the best safety and efficacy profile in the trials conducted so far. Recently, a new EES with a platinum-based platform (PtCr-EES) has been introduced in the market. There is only one study comparing both stents, but with important exclusion criteria. Objectives. We sought to evaluate clinical outcomes with the PtCr-EES compared with the CoCr-EES in an all-comers population. We have conducted a randomized all-comers study aimed to compare these stents in a real-practice scenario. Methods. A total of 300 patients undergoing revascularization and suitable for long-term dual-antiplatelet therapy were randomized 1:1 to CoCr-EES or PtCr-EES. No exclusion criteria based on clinical presentation or lesion characteristics were applied. Results. The clinical and angiographic characteristics were well balanced in both groups without significant differences. At 18 months, the survival free from death and infarction was 93.9% for CoCr-EES and 91.3% for PtCr-EES (P=.3), the survival free from revascularization was 95.2% vs 94.5% (P=.6) and the survival free from death, infarction, and revascularization was 90.6% vs 88%,  respectively (P=.4). The incidence of definite or probable thrombosis was 1.3% for CoCr-EES and 0.66% for PtCr-EES (P=.9). No cases of longitudinal stent compression were observed. Conclusions. The results of this all-comers trial do not show significant differences between CoCr-EES and PtCr-EES. However, the sample size is not powered to exclude potential differences between stents.

J INVASIVE CARDIOL 2013;25(4):182-185

Key words: coronary, drug-eluting stents

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Everolimus-eluting stents (EESs) with a chromium-cobalt platform (CoCr-EES) have shown a lower incidence of clinical restenosis, as well as stent thrombosis, compared to first-generation drug-eluting stents (DESs).^1-5 In the past years, a new EES (Promus Element; Boston Scientific) has been launched. The differentiating aspect of this stent is an innovative platform based on chromium-platinum, PtCr-EES. In the PLATINUM study, the PtCr-EES was shown to be non-inferior to the CoCr-EES within a setting of major clinical and angiographic selection.⁶ However, some cases of longitudinal compression or shortening have been described with these stents.⁷ Bench testing studies addressing this issue have also been recently published.⁸ 

In order to evaluate the efficacy and safety of the PtCr-EES in all clinical and lesion scenarios, we have conducted a comparative randomized study versus the CoCr-EES in a non-selected population. 

Methods

Population. The study included patients referred to the interventional cardiology unit with clinical indication of percutaneous revascularization, who met the following criteria: (1) over 18 years old; (2) considered adequate candidates for double-antiplatelet therapy during 12 months (eg, no chronic oral anticoagulation, no programmed surgical procedures at short-medium term, and no high risk of hemorrhage); (3) not being in cardiogenic shock status; and (4) lack of conditions that would determine a life expectancy of less than 2 years. No other exclusions, either clinical or angiographic, were considered. 

Randomization was conducted after the angiography was seen and the indication for percutaneous revascularization was established. Those patients who met the inclusion criteria and granted their consent for the study were randomized 1:1 according to an electronic method for random number generation. Once the stent model had been assigned, patients were treated in all of their lesions with this type of stent.  

The PCI procedure was always conducted according to the judgment of the operating physician. The same physician decided whether to use predilation, postdilation, intravascular ultrasound, thrombus extraction devices, rotational ablation, or IIb/IIIa receptor inhibitors. Generally, patients received an oral loading dose with 600 mg of clopidogrel, prior to PCI in cases with ACS, or immediately after the procedure in stable cases. Unfractionated heparin was used during PCI, and abciximab was administered in primary PCI cases when not contraindicated. At discharge, the patients were prescribed aspirin (100 mg/day) and clopidogrel (75 mg/day) during a period of 12 months.  

Cardiac enzyme determination was not systematically done after the procedure, except in those cases with clinical indication based on angiographic results or subsequent symptomatic and electrocardiographic evolution. 

Clinical follow-up was conducted at 6 and 12 months after the procedure, through direct contact with the patient, and through the review of electronic patient records generally available in the center. The study was approved by the local clinical trial committee, and patients signed the relevant informed consent. 

Definitions. Major cardiac events were defined as follows. Cardiac death, defined as any death where a cardiac cause can be determined, and those deaths where no etiology can be determined. Infarction was defined as typical increase and gradual fall (troponin), or a faster increase and fall (CK-MB) of biochemical markers for myocardial necrosis with at least one of the following: ischemic symptoms, development of pathological Q-waves in the electrocardiogram (ECG), changes in the ECG indicating ischemia (ST-segment elevation or depression), or pathological results of acute myocardial infarction. Revascularization was defined as a new revascularization procedure, conducted at any level of the coronary tree. Revascularization of the treated lesion was defined as a revascularization upon a restenotic lesion, including the stent and the 5 mm of vessel adjacent to the stent. Definite or probable stent thrombosis were defined according to the definitions by the Academic Research Consortium.

Statistical analysis. Continuous variables are presented as mean ± standard deviation. Categorical variables are expressed as percentages. Continuous variables were compared with the t-test if they followed a normal distribution, and with Wilcoxon tests when they did not (assessment of type of distribution by the Kolmogorov-Smirnov test). The categorical variables were compared with chi-square test or Fischer’s exact test, according to indication. Kaplan-Meier curves for event-free survival were obtained for each group and compared through the log-rank test. A P<.05 was considered statistically significant. The SPSS 15.0 statistical package was used.

Results

Between December 2009 and December 2010, a total of 300 patients were included in the study, 150 treated with PtCr-EES and 150 treated with CoCr-EES. Clinical and angiographic characteristics, as well as the procedure data, are described in Tables 1, 2, and 3. No significant differences were found between groups for the different clinical variables. Patients often had a history of previous revascularization or infarction, and almost a quarter of them presented with an ST-elevation myocardial infarction. Angiographic and procedure data, as well as characteristics of the treated lesions, were also comparable between both groups, and they revealed a standard clinical practice population. The angiographic severity of lesions was very similar, and half of the lesions treated in each group had at least one feature involving a higher risk of restenosis. 

During procedures, no stent shortening or deformation were observed, or at least were not evident either in angiography or intravascular ultrasound examination, when performed.

The use of IVUS to optimize the implantation results was very similar in both groups. Actions taken after IVUS examination were also alike in both groups: postdilatation (66% in CrCo-EES and 63.6% in PtCr-EES group) and additional stent implantation (12.5% in CrCo-EES and 9% in PtCr-EES group). The use of IVUS in this study was centralized in procedures done over aorto-ostial lesions, left main coronary artery, and bifurcations. IVUS was performed in all aorto-ostial treated lesions, 12 in the CrCo-EES group and 15 in the PtCr-EES group. None of them showed incomplete lesion coverage or any kind of longitudinal stent shortening after implantation and eventual postdilatation.

Intraprocedural (and sometimes transient) complications, such as dissection, side-branch occlusion, or no-reflow phenomenon, occurred in 12 in the CrCo-EES group (8%) and 11 in the PtCr-EES group (7.3%). Among these, 10 patients in the CrCo-EES group and 8 patients in the PtCr-EES group showed troponin I increase (above the 99% upper reference limit in those with normal baseline values or a rise >20% in those with stable or falling values). 

There was a median follow-up of 635 days (interquartile range [IQR], 564-715 days); all patients were followed for over 1 year, with none lost to follow-up. Patients complied with their prescribed antiplatelet therapy, which was only temporarily interrupted in a few cases after an hemorrhagic event. Table 4 shows the major adverse cardiac events that occurred in each group and the corresponding cumulative survival free from events. The survival curves for the combined endpoint are shown in Figure 1. The rate for each event was highly comparable between both groups. It is worth noting a TLR rate below 3% for both groups. All revascularizations occurring during the follow-up were percutaneous. Definite and probable stent thrombosis were also very infrequent in both groups, with no very late thrombosis cases. Eleven hemorrhagic events were reported, 6 in the CoCr-EES group (4%) and 5 in the PtCr-EES group (3.3%); there was only 1 intracranial bleeding and none of the events were lethal. Regarding the timing of bleeding, only 1 event occurred during the first month after implantation (21 days), and another occurred after 1 year. No thrombosis or infarctions followed the temporary withdrawal of the dual-antiplatelet therapy. There were 9 strokes, 5 in the CoCr-EES group (3.3%) and 4 in the PtCr-EES group (2.6%); none were fatal.  

Discussion

The main findings of this study are: (1) the PtCr-EES shows a safety profile in implantation very similar to that of the CoCr-EES in an unrestricted clinical and lesion setting with no evident mechanical alterations observed after deployment; and (2) both stents are associated with a comparable incidence of clinical restenosis as well as of stent thrombosis at 18 months of follow-up.

Many studies and subsequent meta-analyses have pointed out that CcCr-EES clinical results are superior to those of first-generation DESs, and particularly PESs, in terms of efficacy (lower target lesion revascularization) and safety (less stent thrombosis).^1-5

Recently, a new model of stent has been included in the cath labs which shares with CcCr-EES the same drug and polymer, but with a different metallic platform: this is the PtCr-EES. This stent has a chromium-platinum platform with architecture that differs from the one used in the Co-Cr EES. This new design is intended to improve the mechanical properties of CoCr stents (high conformability, high crossability, elasticity, access to collateral branches, radio-opacity, radial strength, and resistance to fractures). The everolimus-eluting model assessed in this study has already been compared with CoCr-EES in the PLATINUM study, with 1530 patients in a non-inferiority design.⁶ This study was restrictive, and various exclusion criteria were taken into account, both clinical (eg, infarction) and angiographic (lesions >24 mm, vessels <2.5 mm, occlusions, bifurcations, restenosis, or lesions in very winding or calcified segments). Therefore, it included a profile of lesions with low risk of restenosis. This study showed non-inferiority for the new stent, with an incidence of MACE at 12 months very similar to that for the Co-Cr EES. The authors of this study acknowledged the limitations created by the selection bias, and pointed out the need for an “all-comers” study in order to better assess this stent model.⁶ A non-randomized analysis from the Swedish angioplasty registry suggests comparable outcomes with PtCr-EES compared to other DESs regarding restenosis and thrombosis.⁹

When the use of this stent became widespread, some cases of an excessive longitudinal stent shortening were reported.⁷ This event has also been observed in other stent models, but some groups have suggested that its incidence might be higher with this specific type of stent, attributing this to certain specific features of its architecture. A bench-top study has provided insight into this problem.⁸ The authors found a relationship between the number of stent connectors between hoops and the force required for longitudinal compression and elongation. Stents with two connectors, like the Omega platform of the Promus Element and the Driver platform of the Endeavor Resolute, are deformed under less force than those with more connectors.

Considering everything mentioned thus far, it seemed relevant to evaluate this model of stent in a non-restrictive clinical practice setting, in all types of lesions and scenarios. In our study, patients have been randomized, with practically no clinical or angiographic exclusions, to both types of stents. Outcomes at 1 year show a great similarity in terms of incidence of all MACE. No events of longitudinal shortening were observed in this study in either group. The use of IVUS in all aorto-ostial lesions treated in the left main and right coronary artery allowed us to exclude that kind of deformation at that level. Moreover, the increased radio-opacity of this stent, along with its high flexibility and radial force, makes it a good choice for treating this specific lesion type. The visibility of the stent could also prove interesting for the treatment of bifurcations or in spot-stenting approaches.

These longitudinal deformations probably appear in a very low proportion, with different stent models, and are associated with very specific anatomical and procedural scenarios. Some case reports present stent deformations occurring under aggressive manipulations of guiding catheters over eventually malapposed stents. On the other hand, the enhanced radio-opacity of these stents makes it easier to point out a deformation that could remain otherwise undetected.

Study limitations. Undoubtedly, the major limitation of this study lies in its limited size. It lacks statistical power to establish even non-inferiority between the models of stents studied. However, the great similarity observed in clinical outcomes, in an open setting and with no restrictions in application, suggests a similar performance between both. Regarding the incidence of deformation events, specifically in terms of longitudinal shortening, once again the study has a very limited size in order to detect any potential differences between both models, and even more for an event with a probably very low rate. At any rate, these results suggest that, even though these alterations are possible, particularly in certain scenarios, their incidence will still be very low. Finally, cardiac enzymes were not routinely measured after interventions, which could have led to an underreporting of peri-post procedural infarctions. 

Conclusions

The results of this all-comers randomized study show very similar clinical outcomes at 1 year in patients treated with the CoCr-EES versus the PtCr-EES. No differences were observed for any type of event. No events of longitudinal shortening of the stent have been detected, at least in an evident manner, in the group with PtCr-EES. However, given the sample size, this study is not powered to exclude potential differences between stents.

Acknowledgments. We are thankful to Virginia Frances Santamaría, RN, and Monica Fernandez Menendez, RN, for their valuable collaboration in this study.

References

1. Planer D, Smits PC, Kereiakes DJ, et al. Comparison of everolimus- and paclitaxel-eluting stents in patients with acute and stable coronary syndromes: pooled results from the SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) trials. JACC Cardiovasc Interv. 2011;4(10):1104-1115.
2. Baber U, Mehran R, Sharma SK, et al. Impact of the everolimus-eluting stent on stent thrombosis: a meta-analysis of 13 randomized trials. J Am Coll Cardiol. 2011;58(15):1569-1577. 
3. Alfonso F, Fernandez C. Second-generation drug-eluting stents. Moving the field forward. J Am Coll Cardiol. 2011;58(1):26-29.
4. Alfonso F, Fernandez C. Head to head randomized comparisons of limus-eluting coronary stents. J Am Coll Cardiol. 2011;58(18):1855-1858.
5. Palmerini T, Biondi-Zoccai G, Riva DD, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379(9824):1393-1402. 2012 Mar 22 (Epub ahead of print).
6. Stone GW, Teirstein PS, Meredith IT, et al. A prospective, randomized evaluation of a novel everolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial. J Am Coll Cardiol. 2011;57(16):1700-1708. 
7. Hanratty CG, Walsh SJ. Longitudinal compression: a new complication with modern coronary stent platforms — time to think beyond deliverability? Eurointervention. 2011;7(7):872-877. 
8. Ormiston JA, Webber B, Webster WI. Stent longitudinal integrity. Bench insights into a clinical problem. JACC Cardiovasc Interv. 2011;4(12):1310-1317.
9. Sarno G, Lagerqvist B, Carlsson J, et al. Initial clinical experience with an everolimus eluting platinum chromium stent (Promus Element) in unselected patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Int J Cardiol. 2012 Jan 12 (Epub ahead of print).

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From the U. de Cardiologia Intervencionista, Cardiologia Valdecilla, Hospital Universitario Marques de Valdecilla, Santander, Spain.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr de la Torre Hernandez reports consulting fees and honoraria from Boston Scientific, Abbott Vascular, Medtronic, Cordis, Volcano, Biotronik, Astra Zeneca, and Lilly. No other authors report any conflicts of interest or financial disclosures regarding the content herein.

Manuscript submitted September 19, 2012, provisional acceptance given October 16, 2012, final version accepted December 17, 2012.

Address for correspondence: Dr Jose M. de la Torre Hernández, Unidad de Hemodinámica y Cardiología Intervencionista, Hospital Universitario Marques de Valdecilla, 39012 Santander, Spain. Email: he1thj@humv.es