Zotarolimus-, Everolimus-Eluting Stents Found Equally Safe, Effective

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.

SAN FRANCISCO – Zotarolimus-eluting stents are generally as safe and effective as everolimus-eluting stents for coronary stenting in the real-world setting, according to results from a randomized, noninferiority phase IV trial comparing them head to head.

Among the 1,391 patients studied, all of whom were treated at the tertiary-care Thoraxcentrum Twente in the Netherlands, about 8% experienced events signaling a failure of the target vessel within a year, no matter which of these second-generation drug-eluting stents they received.

The difference between groups was well within the predefined boundary for noninferiority, lead investigator Dr. Clemens von Birgelen reported at Transcatheter Cardiovascular Therapeutics 2011, which is sponsored by the Cardiovascular Research Foundation. Additionally, both groups had very low and statistically indistinguishable rates of definite or probable stent thrombosis.

The bottom line is that the choice between the two stents will come down to a matter of physicians’ personal preference, he said in an interview. "There are emotional arguments" favoring one stent or the other, Dr. von Birgelen noted. He declined to say whether other factors might give one stent the edge.

The trial’s findings confirm those of the similar Resolute All Comers trial (N. Engl. J. Med. 2010;363:136-46), although that trial was larger and multicenter in nature. Collectively, these data show that "both stents are safe and efficacious, and you can use either one or the other," Dr. von Birgelen maintained. "So the physician has to decide at the end of the day which one to use."

The practice of dilatation after stenting – used in most of the procedures in the new trial – may be important to getting the same results, according to Dr. von Birgelen. "Postdilatation of stents is something to consider in the proximal and mid part [of the lesion] to get good stent apposition, and could be part of the reason why we found such nice results in this study," he explained.

Discussant Dr. Ron Waksman, director of Experimental Angioplasty & Emerging Technologies, Cardiovascular Research Institute in Washington, said, "It’s very hard to differentiate between the stents right now. The data is almost identical ... I think it’s really going to be a question of availability of sizes and lengths, pricing, et cetera, but not in terms of performance of the stent."

Dr. John McB. Hodgson, chairman of the department of cardiology at Geisinger Health System in Wilkes-Barre, Pa., agreed and noted that these second-generation drug-eluting stents are a major technological advance. "Both of these platforms are fantastic compared to what we had 5 years ago. We are splitting hairs – these are both great platforms," he commented.

Patients were eligible for the trial, known as the TWENTE trial and jointly supported by Abbott Vascular and Medtronic, if they had stable angina or a non–ST-elevation acute coronary syndrome plus an indication for implantation of a drug-eluting stent.

The enrolled patients, 82% of all those who were eligible, were randomized in balanced fashion to receive either zotarolimus-eluting stents (Resolute, manufactured by Medtronic and currently investigational in the United States) or everolimus-eluting stents (Xience V, manufactured by Abbott). Patients and data analysts, but not treating clinicians, were blinded to group assignment.

There was no limit on the number of lesions or vessels treated, the lesion length, or the vessel size, noted Dr. von Birgelen, who is a professor at the Thoraxcentrum Twente. All types of lesions, including those in bypass grafts and at bifurcations, were permitted.

The study population was 64 years old on average. About one-fifth of patients had diabetes. The slight majority had acute coronary syndromes. Nearly 25% had multiple vessels treated, and 77% had at least one off-label indication for drug-eluting stent implantation, such as stenting of the left main stem, long lesions, or very small vessels.

Roughly two-thirds of treated lesions were complex, and one-quarter were at bifurcations. The stent was implanted directly, without predilatation of the lesion, in 39% of lesions, a rate similar to that seen in other studies. "Postdilatation, however, was performed particularly often in our center, in 82% of the stented lesions," Dr. von Birgelen noted. "It’s a kind of standard strategy in our center for several years with drug-eluting stents, because we think that the postdilatation leads to better apposition of the stent to the vessel wall, with a better drug transition into the vessel wall, and this could avoid stent thrombosis and other events."

Additionally, use of postdilatation increased as the center began stenting longer lesions, given that coronary vessels naturally taper over their length. "We have to choose a stent of a certain size, and then by postdilatation, try to mimic the biological situation by being more aggressive with postdilatation in the proximal part, somewhat less in the mid part, and then distal," he explained.

Study results showed that both treatment groups had nearly 100% rates of lesion success and 96% rates of procedure success.

In intent-to-treat analyses, the 1-year rate of target vessel failure – a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization – was 8.2% with zotarolimus-eluting stents and 8.1% with everolimus-eluting stents. The absolute difference of 0.1% and upper limit of the one-sided 95% confidence interval of 2.53% were well within the predefined noninferiority margin of 4.48% (P for noninferiority = .001; P for superiority = .94).

The findings were similar across patient subgroups stratified by disease and lesion characteristics, and similar for each of the three components of the composite end point individually.

There was an interaction between treatment group and diabetes status (P = .045), but more-detailed analysis failed to show a significant benefit of one stent over the other. "This is a trend which is hypothesis generating and interesting," Dr. von Birgelen commented. "It may raise some more pooling of data and analysis."

The trial’s main results were much the same when the investigators used a broader, patient-oriented composite end point of all deaths, any myocardial infarction, and any revascularization (11.2% vs. 10.5%; P for superiority = .69).

The zotarolimus- and everolimus-eluting stent groups also had very low and statistically indistinguishable rates of definite or probable stent thrombosis (0.86% vs. 1.16%). These rates are "relatively low, certainly when you consider the complexity of patients and lesions that were studied in this trial," he noted.

"Zotarolimus-eluting Resolute stents were noninferior to everolimus-eluting Xience V stents in terms of safety and efficacy for treating real-world patients with a vast majority of complex lesions and off-label indications for drug-eluting stents, which were implanted with liberal use of postdilatation," Dr. von Birgelen concluded.

Follow-up continues, he added. "It makes sense, and we must learn from the first-generation drug-eluting stents that we should follow up these patients longer than just 1 year. There is a 2-year follow-up already running at this moment, and we will follow these patients even further," he said.

Dr. von Birgelen reported that he is a consultant to and has received speaker honoraria and/or traveling expenses from Abbott Vascular, Medtronic, and Boston Scientific. Dr. Waksman reported that he had no relevant conflicts of interest. Dr. Hodgson reported that he receives research or grant support from Boston Scientific, Volcano, and St. Jude Medical, and that he is a consultant to, is a speaker for, or receives honoraria from Volcano.