The <scp>SYNERGY</scp> biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study

Wilson, Gregory J.; Marks, Angela; Berg, Kimberly J.; Eppihimer, Michael J.; Sushkova, Natalia; Hawley, Steve; Robertson, Kimberly; Knapp, David A.; Pennington, Douglas; Chen, Yen-Lane; Foss, Aaron; Huibregtse, Barbara; Dawkins, Keith D.

doi:10.1002/ccd.25993

Cited by 44 publications

(26 citation statements)

References 14 publications

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“…Moreover, both release their drug loads prior to full coating absorption, rendering their comparison even more relevant. SYNERGY releases 50 and >95% of its drug load by 28 and 90d, 28 slower than durable coated Cypher SES, while O3FA DES achieves these targets by 5 h and 8d. Moreover, whereas the O3FA DES coating begins to rapidly absorb upon implantation with only 15% remaining at 8d, the PLGA coating is relatively biostable up to 28d and achieves 85% erosion only after 90d.…”

Section: Discussionmentioning

confidence: 98%

“…Correspondingly, SYNERGY stents provide a near constant Everolimus concentration in subjacent tissue, 1–2 μ g/g, between 5 and 90d, 28 whereas tissue levels of Corolimus were only detectable up to 56d post O3FA DES implantation. Correspondingly, the published 90d data for the O3FA are non-inferior and perhaps better than SYNERGY under overlap in pig coronary arteries 28 (0.21 ± 0.14 mm vs. 0.46 ± 0.22 neointimal thickness and 29.29 ± 13.72 vs. 46.15 ± 18.03% stenosis. Thus, a comparison of O3FA DES to SYNERGY is supportive of our hypothesis that biocompatibility of O3FA compared favorably to synthetic polymers such as PLGA and (B) that there is an advantage to delivering Sirolimus analog Corolimus at a fast rate compared to Cypher.…”

Section: Discussionmentioning

confidence: 99%

“…Yet despite the seeming diversity in emerging DES designs, most—including fourth generation stents with bioerodible coatings (e.g., SYNERGY 28 )—are designed to follow the Cypher SES paradigm of sustained drug elution and tissue retention. The current study illustrates that retention of Sirolimus analogs can be achieved even with fast drug elution kinetics following rapid coating erosion, with computational modeling identifying binding to tissue receptors as the mechanism of prolonged retention.…”

Section: Discussionmentioning

confidence: 99%

“…Both SYNERGY and O3FA DES have thin struts (74 vs. 85 μ m), and employ an erodible coating to elute similar loads of distinct Sirolimus analogs (5.7 μ g/mm Everolimus 28 vs. 5.8 μ g/mm Corolimus). Moreover, both release their drug loads prior to full coating absorption, rendering their comparison even more relevant.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, whereas the O3FA DES coating begins to rapidly absorb upon implantation with only 15% remaining at 8d, the PLGA coating is relatively biostable up to 28d and achieves 85% erosion only after 90d. 28 …”

Section: Discussionmentioning

confidence: 99%

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Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

et al. 2015

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The long held assumption that sustained drug elution from stent coatings over weeks to months is imperative for clinical efficacy has limited the choice for stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA) based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug levels in porcine coronary arteries similarly to those achieved by slow-eluting durable coated Cypher Select Plus Stents and with significantly lower levels of granuloma formation and luminal stenosis. Computational modeling confirmed that diffusion and binding constants of Corolimus and Sirolimus are identical and explained that the sustained retention of Corolimus was facilitated by binding to high affinity intracellular receptors (FKBP12). First in man outcomes were positive—unlike Cypher stents where late lumen loss drops over 6 month, there was a stable effect without diminution in the presence of O3FA. These results speak to a new paradigm whereby the safety of drug eluting stents can be optimized through the use of resorbable biocompatible coating materials with resorption kinetics that coincide with the dissociation and tissue elimination of receptor-bound drug.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

et al. 2015

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P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent

Min,

Kang,

Cho

et al. 2024

JAMA Netw Open

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ImportanceP2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent.ObjectiveTo investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent.Design, Setting, and ParticipantsThe Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled.InterventionsPatients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693).Main Outcomes and MeasuresThe primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%.ResultsOf the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, −0.93 [1-sided 95% CI, −2.64 to 0.77] percentage points; P &lt; .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, −0.49 [95% CI, −2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, −0.60 [95% CI, −1.33 to 0.12] percentage points; P = .10).Conclusions and RelevanceIn patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations.Trial RegistrationClinicalTrials.gov Identifier: NCT03447379

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Real‐life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Sarno

Lagerqvist

Olivecrona

et al. 2017

Cathet Cardio Intervent

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The SYNERGY biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study

Abstract: In a swine model, everolimus was released by 90 days and PLGA bioabsorption was complete shortly thereafter. The SYNERGY stent and its biodegradable polymer, even at a 3× safety margin, demonstrated vascular compatibility similar to bare metal stent controls.

Cited by 44 publications

References 14 publications

Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent

Real‐life clinical outcomes with everolimus eluting platinum chromium stent with an abluminal biodegradable polymer in patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

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