Biodegradable Stent May Lower Late Thrombosis Risk

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.

SAN FRANCISCO – Biodegradable drug-eluting stents are noninferior to durable drug-eluting stents and may improve long-term outcomes, based on 4-year results from the first large, randomized clinical trial of these devices.

A biodegradable polymer biolimus-eluting stent (BioMatrix Flex) was as effective in treating patients with chronic stable coronary artery disease or acute coronary syndromes as a durable polymer sirolimus-eluting stent (Cypher Select), and seemed to reduce the risk of very late stent thrombosis; however, the study was not powered to detect differences in late stent thrombosis.

In the randomized, multicenter study, 2,472 lesions were treated in 1,707 patients. Investigators initially found that a biodegradable polymer biolimus-eluting stent (BES) was noninferior to a durable polymer sirolimus-eluting stent (SES) in the risk for major clinical events at 9 months (Lancet 2008;372:1163-73).

After 4 years of follow-up, 19% of patients in the biodegradable stent group and 23% in the durable stent group met a composite primary end point of cardiac death, MI, or clinically indicated target vessel revascularization, a difference that again was not statistically significant between groups, reported Dr. Patrick W. Serruys of Erasmus University, Rotterdam, the Netherlands.

The rates of cardiac death were 7% with biodegradable stents and 6% with durable stents, and MI rates were 8% and 9%, Dr. Serruys reported. Combining those two end points, 12% in the biodegradable stent group and 15% in the durable stent group had an MI or a cardiac death by year 4. Target vessel revascularization was clinically indicated in 11% of the biodegradable stent group and 14% of the durable stent group by year 4.

Patients who got the biodegradable stent had a 38% lower risk for definite stent thrombosis at 4 years than did patients in the durable stent group. The stent thrombosis risk overall and in the first year was not statistically significant between groups, but a significant difference emerged after the first year of follow-up, reported Dr. Thomas A. Ischinger of Kardiologie im Zentrum, Munich.

In the first year, the risk for definite stent thrombosis was only 1% lower in the BES group than in the SES group, but in subsequent years, the risk for very late stent thrombosis (after 1 year or more) was 80% lower in the biodegradable stent group than in the durable stent group. The difference in risk for very late thrombosis was statistically significant (P = .004).

The rates of very late stent thrombosis were 0.12% per year in the biodegradable stent group and 0.6% per year in the durable stent group. Previous studies have shown that the rate of definite stent thrombosis with early-generation drug-eluting stents is 0.53% per year, Dr. Ischinger noted.

The investigators and their associates reported the findings on Nov. 8 in two separate presentations at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation. The findings also were simultaneously published online (Lancet 2011 [doi:10.1016/S0140-6736(11)61672-3]) by lead author Dr. Giulio G. Stefanini of the University of Bern (Switzerland) and his associates.

The trial accepted all comers, including 16% of patients in the biodegradable stent group and 17% in the durable stent group who had ST-segment elevation MI.

The study, known as the LEADERS trial (Limus Eluted From a Durable Versus Erodable Stent Coating) found a 2.4% rate of definite stent thrombosis in the biodegradable stent group and a 4% rate in the durable stent group at 4 years, compared with rates of 2% in each group at 1 year. Between years 1 and 4, the rates of definite stent thrombosis were 0.4% in the biodegradable stent group and 2% in the durable stent group, Dr. Ischinger reported.

Separation of Kaplan Meier curves between years 1 and 4 support these findings "and suggests that, over time, a differential exists between the two stents," Dr. Ron Waksman and Dr. Gabriel Maluenda of Washington (D.C.) Hospital Center wrote in an editorial accompanying the article (Lancet 2011 [doi:10.1016/S0140-6736(11)61706-6]).

They called the differences in rates of late stent thrombosis "intriguing."

Dr. Waksman and Dr. Maluenda cautioned that LEADERS was not designed as a superiority trial, and long-term differences in major adverse clinical events "should be carefully interpreted when translating [them] to clinical practice."

Biodegradable polymer drug-eluting stents have been developed to try and avoid the delayed arterial healing and subsequent late adverse events, such as stent thrombosis, reported with durable polymer drug-eluting stents compared with bare-metal stents. Biolimus, a semi-synthetic sirolimus analogue with 10 times higher lipophilicity and similar potency, is immersed into a biodegradable polymer in the BioMatrix Flex stent.

The idea behind putting biodegradable polymers in stents is that, after degradation, the stent will be polymer free and drug free like a bare-metal stent.

It is unknown whether the LEADERS trial results are specific to the stents used in the trial or apply to other biodegradable stents, which vary in their rates of degradation from 3 months to up to 2 years. The biodegradable polymer in the BioMatrix stent metabolizes to water and carbon dioxide in 6-9 months.

It’s also unclear how biodegradable stents stack up against second-generation drug-eluting stents, which produce fewer adverse events. The long-term results of LEADERS are encouraging, but it will take another 5 years or more of studies to determine if they are superior to second-generation drug-eluting stents, Dr. Waksman and Dr. Maluenda said.

Dr. Stefanini and his associates wrote that the LEADERS results provide "the basis of a proof of concept" for better clinical outcomes with the biodegradable stent versus the durable stent by reducing the risk of very late stent thrombosis. This may have implications for recommendations regarding the duration of dual antiplatelet therapy after stent implantation, they added.

A 5-year follow-up of patients in the LEADERS trial is planned. Dr. Serruys said a global LEADERS study is underway that will compare two antiplatelet therapy regimens after implantation of the BioMatrix stent. Patients will be randomized to very short dual antiplatelet therapy combining 1 month of aspirin and 23 months of ticagrelor monotherapy or to dual therapy with those two drugs for 12 months followed by aspirin monotherapy for 12 months.

In the LEADERS trial, adherence to dual antiplatelet therapy did not differ between groups.

The study was funded by Biosensors Europe, which makes the BioMatrix stent. Dr. Serruys, Dr. Ischinger, Dr. Stefanini, and Dr. Maluenda reported having no relevant financial disclosures. For other investigators in the study, disclosures can be found in the Lancet article. Dr. Waksman has been a consultant to and speaker for Biotronik, Medtronic, Boston Scientific, the Medicines Company, and AstraZeneca, and has received research funding from most of those companies plus Schering-Plough, Sanofi-Aventis, and GlaxoSmithKline.