Biodegradable Polymer DES Reduce the Risk of Stent Thrombosis
Biodegradable Polymer DES Reduce the Risk of Stent Thrombosis
Aims The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES).
Methods and results We pooled individual patient data from three large-scale multicentre randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) comparing biodegradable polymer DES with durable polymer SES and assessed clinical outcomes during follow-up through 4 years. The efficacy endpoint of interest was target lesion revascularization and the safety endpoint of interest was definite stent thrombosis. Out of 4062 patients included in the present analysis, 2358 were randomly assigned to treatment with biodegradable polymer DES (sirolimus-eluting, n= 1501; biolimus-eluting, n= 857) and 1704 patients to durable polymer SES. No heterogeneity across the trials was observed in analyses of the primary and secondary endpoints. At 4 years, the risk of target lesion revascularization was significantly lower among patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.82, 95% CI 0.68–0.98, P= 0.029). In addition, the risk of stent thrombosis was significantly reduced with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.56, 95% CI 0.35–0.90, P= 0.015), driven by a lower risk of very late stent thrombosis (hazard ratio 0.22, 95% CI 0.08–0.61, P= 0.004). In keeping with this, in landmark analysis between 1 and 4 years, the incidence of myocardial infarction was lower for patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.59, 95% CI 0.73–0.95, P= 0.031).
Conclusion Biodegradable polymer DES improve safety and efficacy compared with durable polymer SES during long-term follow-up to 4 years.
Drug-eluting stents (DES) with controlled release of anti-proliferative drugs from durable polymer coatings provide potent suppression of neointimal hyperplasia and markedly reduced the risk of repeat revascularization compared with bare metal stents. However, the use of early generation durable polymer DES was associated with an increased risk of very late (>1 year) stent thrombosis compared with bare metal stents. Animal experiments, human autopsy studies, and investigation of thrombosed DES specimens using intravascular ultrasound demonstrated that very late ST is related to delayed arterial healing and remodelling of the stented vessel owing to ongoing inflammation. The persistence of durable polymer coatings after completion of the drug release has been implicated as a potential culprit for this chronic inflammatory response.
Biodegradable polymer-based DES, with controlled drug-release followed by subsequent degradation of the polymer coating, may potentially improve long-term clinical outcomes after coronary stenting, by rendering the stent surface similar to that of a bare metal stent and free of a chronic inflammatory stimulus. Biodegradable polymer-based DES have been established as a safe and effective alternative to durable polymer-based stent platforms as evidenced in several randomized clinical trials. Moreover, an optical coherence tomography study suggested improved healing of the stented coronary segment following treatment with biodegradable polymer DES compared with durable polymer sirolimus-eluting stents (SES) at 9 months. However, the potential clinical advantage of biodegradable polymer DES over durable polymer DES may be expected to emerge first after long-term follow-up, where the incidence of late adverse events related to impaired vessel healing—such as stent thrombosis—is hypothesized to be lower. Against this background, we pooled results from the three largest randomized clinical trials comparing biodegradable polymer DES with durable polymer SES incorporating clinical follow-up to 4 years.
Abstract and Introduction
Abstract
Aims The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES).
Methods and results We pooled individual patient data from three large-scale multicentre randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) comparing biodegradable polymer DES with durable polymer SES and assessed clinical outcomes during follow-up through 4 years. The efficacy endpoint of interest was target lesion revascularization and the safety endpoint of interest was definite stent thrombosis. Out of 4062 patients included in the present analysis, 2358 were randomly assigned to treatment with biodegradable polymer DES (sirolimus-eluting, n= 1501; biolimus-eluting, n= 857) and 1704 patients to durable polymer SES. No heterogeneity across the trials was observed in analyses of the primary and secondary endpoints. At 4 years, the risk of target lesion revascularization was significantly lower among patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.82, 95% CI 0.68–0.98, P= 0.029). In addition, the risk of stent thrombosis was significantly reduced with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.56, 95% CI 0.35–0.90, P= 0.015), driven by a lower risk of very late stent thrombosis (hazard ratio 0.22, 95% CI 0.08–0.61, P= 0.004). In keeping with this, in landmark analysis between 1 and 4 years, the incidence of myocardial infarction was lower for patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.59, 95% CI 0.73–0.95, P= 0.031).
Conclusion Biodegradable polymer DES improve safety and efficacy compared with durable polymer SES during long-term follow-up to 4 years.
Introduction
Drug-eluting stents (DES) with controlled release of anti-proliferative drugs from durable polymer coatings provide potent suppression of neointimal hyperplasia and markedly reduced the risk of repeat revascularization compared with bare metal stents. However, the use of early generation durable polymer DES was associated with an increased risk of very late (>1 year) stent thrombosis compared with bare metal stents. Animal experiments, human autopsy studies, and investigation of thrombosed DES specimens using intravascular ultrasound demonstrated that very late ST is related to delayed arterial healing and remodelling of the stented vessel owing to ongoing inflammation. The persistence of durable polymer coatings after completion of the drug release has been implicated as a potential culprit for this chronic inflammatory response.
Biodegradable polymer-based DES, with controlled drug-release followed by subsequent degradation of the polymer coating, may potentially improve long-term clinical outcomes after coronary stenting, by rendering the stent surface similar to that of a bare metal stent and free of a chronic inflammatory stimulus. Biodegradable polymer-based DES have been established as a safe and effective alternative to durable polymer-based stent platforms as evidenced in several randomized clinical trials. Moreover, an optical coherence tomography study suggested improved healing of the stented coronary segment following treatment with biodegradable polymer DES compared with durable polymer sirolimus-eluting stents (SES) at 9 months. However, the potential clinical advantage of biodegradable polymer DES over durable polymer DES may be expected to emerge first after long-term follow-up, where the incidence of late adverse events related to impaired vessel healing—such as stent thrombosis—is hypothesized to be lower. Against this background, we pooled results from the three largest randomized clinical trials comparing biodegradable polymer DES with durable polymer SES incorporating clinical follow-up to 4 years.
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