Michael Barbella, Managing Editor04.13.21
Elixir Medical's INFINITY-SWEDEHEART clinical study is now officially underway.
The randomized controlled trial (RCT) enrolled 2,400 patients to study the DynamX Coronary Bioadaptor System, the first metallic coronary artery implant that adapts to vessel physiology.
“Drug-eluting stents have been very useful in opening blocked arteries, but the rigid stent structure cages the artery, impacting its ability to respond to disease progression and maintain blood flow lumen, as it would otherwise do naturally,” said Professor David Erlinge, M.D., Ph.D., FESC, FACC, Lund University, Lund, Sweden, the study's principal investigator. “We are enthusiastic about studying the novel DynamX device, which is the first metallic device treating coronary artery disease that has been shown to restore pulsatility and positive adaptive remodeling of coronary arteries. The benefits of restored vessel function may provide greater benefit in patients with complex disease. The INFINITY-SWEDEHEART study includes these complex patients with both Chronic Coronary Syndrome and Acute Coronary Syndrome.”
The INFINITY-SWEDEHEART RCT is a prospective, multicenter, single-blind, randomized study enrolling 2,400 patients at approximately 20 sites in Sweden treated with the DynamX Bioadaptor in a 1:1 randomization to Resolute Onyx, a leading drug-eluting stent (DES). The study design utilizes the rigorous SWEDEHEART registry database to support patient follow-up. The primary endpoint of the study is a device-oriented clinical endpoint (DOCE) of non-inferiority of target lesion failure (TLF), a composite endpoint that includes cardiovascular death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization, at one year. Powered secondary endpoints include superiority in the overall population and pre-specified sub-groups, including small vessel, long lesions, left anterior descending artery (LAD), chronic angina and diabetes. Professor Stefan James, M.D., Ph.D., FESC, FACC, Uppsala University Hospital, Uppsala, Sweden, chairs the Executive Steering Committee for the trial.
The DynamX Bioadaptor is a metal implant with a drug-eluting bioresorbable polymer coating that supports the coronary artery during healing, with radial strength similar to DES. Over six months, the polymer coating dissolves, uncaging the bioadaptor and freeing the artery to move with the natural expansion and contraction of the artery, unlike DES. This has been shown to (a) maintain the ability for positive adaptive remodeling, (b) restore vessel function, and (c) allow for the vessel’s return toward baseline angulation.1
The bioadaptor is designed to address the major adverse cardiac event (MACE) rate that occurs with drug-eluting stents each year without plateau.2,3,4 The rigid design of a DES constrains, or “cages,” natural artery movement, restricting its natural ability to accommodate disease progression. This has been associated with MACE.5 Studies have shown adverse event rates associated with DES of 20 percent at five years2 and 40 to 50 percent at 10 years.3 Published papers have demonstrated that a DES prevents positive adaptive remodeling,6 inhibits vessel compliance and dilation in response to the body’s changing blood flow needs,7,8 and causes vessel straightening, which has been associated with increased MACE.9
"Swedish quality registries, including SWEDEHEART, have been utilized by Uppsala Clinical research center (UCR) for a number of groundbreaking cardiovascular clinical trials and it is appropriate that a unique device such as the DynamX device would be evaluated in a large number of patients using its infrastructure,” said Professor James. “We have found the device as easy to deliver as a stent, but with the potential to reduce long-term DES-associated risks and improve upon patient outcomes over time.”
The DynamX Bioadaptor has been shown to improve vessel function1 in several ways. It enables the vessel to accommodate disease progression and achieve positive adaptive remodeling by increasing vessel area and maintaining lumen diameter, which preserves blood flow to the heart. DynamX restores vessel function and allows for normal vessel pulsatility and motion, enabling it to provide more blood flow in response to the body’s needs during physical activity. It also allows the vessel to return to baseline angulation, which may reduce adverse events.
“The INFINITY-SWEDEHEART RCT utilizing the respected SWEDEHEART registry database is an efficient approach to conducting an evidence-based trial, and provides important benefits. For the first time, we will be able to compare the performance of the physiologically-adaptive DynamX against an industry-leading DES in the overall study population and in subsets of patients. In addition, by leveraging the existing rigorous SWEDEHEART registry database, we will be able to conduct the trial and follow-up with high quality, efficiency and speed,” said Motasim Sirhan, Elixir Medical’s CEO.
The DynamX Coronary Bioadaptor System is CE Mark approved. It is not available for sale in the United States.
References
1 Verheye S, Vrolix M, Montorfano M, Zivelonghi C, Giannini F, Bedogni F, et al. Twelve-month clinical and imaging outcomes of the uncaging coronary DynamX Bioadaptor. EuroIntervention 2020;16;e974-e981
2 Iqbal J, Serruys PW, Silber S, et al. Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-comers trial. Circ Cardiovasc Interv. 2015;8(6):e002230. doi:10.1161/CIRCINTERVENTIONS.114.002230
3 Kufner S, Joner M, Thannheimer A, Hoppmann P, Ibrahim T, Mayer K, et al. Ten-year clinical outcomes from a trial of three limus-eluting stents with different polymer coatings in patients with coronary artery disease: results from the ISAR-TEST 4 randomized trial. Circulation. 2019; 139:325–333. doi: 10.1161/CIRCULATIONAHA.118.038065.
4 Smits, PC, Valchojannis, GJ, McFadden, EP, et al. Final 5-year follow-up of a randomized controlled trial of everolimus- and paclitaxel-eluting stents for coronary revascularization in daily practice. J Am Coll Cardiol Intv. 2015 Aug, 8 (9) 1157-1165.
5 Stone GW, Kimura T, Gao R, et al. Time-varying outcomes with the Absorb Bioresorbable Vascular Scaffold during 5-year follow-up: a systematic meta-analysis and individual patient data pooled study. JAMA Cardiol. 2019;4(12):1261–1269. doi:10.1001/jamacardio.2019.4101
6 Nakamura M, Yock PG, Bonneau HN, et al. Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study. Circulation. 2001;103(17):2130-2132. doi:10.1161/01.cir.103.17.2130
7 Maier, W, Windecker, S, Kung, A, et al. Exercise-induced coronary artery vasodilation is not impaired by stent placement. Circulation. 2002; 105(20): 2373-2377. doi: 10.1161/01.cir.0000016360.97819.44
8 Hamilos, M, Sarma, J, Ostojic, M, et al. (2008). Interference of drug-eluting stents with endothelium-dependent coronary vasomotion evidence for device-specific responses. Circ Cardiovasc Interv. 1. 193-200. 10.1161/CIRCINTERVENTIONS.108.797928.
9 Gyöngyösi M, Yang P, Khorsand A, Glogar D. Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events. Austrian Wiktor Stent Study Group and European Paragon Stent Investigators. J Am Coll Cardiol. 2000;35(6):1580-1589. doi:10.1016/s0735-1097(00)00570-2
The randomized controlled trial (RCT) enrolled 2,400 patients to study the DynamX Coronary Bioadaptor System, the first metallic coronary artery implant that adapts to vessel physiology.
“Drug-eluting stents have been very useful in opening blocked arteries, but the rigid stent structure cages the artery, impacting its ability to respond to disease progression and maintain blood flow lumen, as it would otherwise do naturally,” said Professor David Erlinge, M.D., Ph.D., FESC, FACC, Lund University, Lund, Sweden, the study's principal investigator. “We are enthusiastic about studying the novel DynamX device, which is the first metallic device treating coronary artery disease that has been shown to restore pulsatility and positive adaptive remodeling of coronary arteries. The benefits of restored vessel function may provide greater benefit in patients with complex disease. The INFINITY-SWEDEHEART study includes these complex patients with both Chronic Coronary Syndrome and Acute Coronary Syndrome.”
The INFINITY-SWEDEHEART RCT is a prospective, multicenter, single-blind, randomized study enrolling 2,400 patients at approximately 20 sites in Sweden treated with the DynamX Bioadaptor in a 1:1 randomization to Resolute Onyx, a leading drug-eluting stent (DES). The study design utilizes the rigorous SWEDEHEART registry database to support patient follow-up. The primary endpoint of the study is a device-oriented clinical endpoint (DOCE) of non-inferiority of target lesion failure (TLF), a composite endpoint that includes cardiovascular death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization, at one year. Powered secondary endpoints include superiority in the overall population and pre-specified sub-groups, including small vessel, long lesions, left anterior descending artery (LAD), chronic angina and diabetes. Professor Stefan James, M.D., Ph.D., FESC, FACC, Uppsala University Hospital, Uppsala, Sweden, chairs the Executive Steering Committee for the trial.
The DynamX Bioadaptor is a metal implant with a drug-eluting bioresorbable polymer coating that supports the coronary artery during healing, with radial strength similar to DES. Over six months, the polymer coating dissolves, uncaging the bioadaptor and freeing the artery to move with the natural expansion and contraction of the artery, unlike DES. This has been shown to (a) maintain the ability for positive adaptive remodeling, (b) restore vessel function, and (c) allow for the vessel’s return toward baseline angulation.1
The bioadaptor is designed to address the major adverse cardiac event (MACE) rate that occurs with drug-eluting stents each year without plateau.2,3,4 The rigid design of a DES constrains, or “cages,” natural artery movement, restricting its natural ability to accommodate disease progression. This has been associated with MACE.5 Studies have shown adverse event rates associated with DES of 20 percent at five years2 and 40 to 50 percent at 10 years.3 Published papers have demonstrated that a DES prevents positive adaptive remodeling,6 inhibits vessel compliance and dilation in response to the body’s changing blood flow needs,7,8 and causes vessel straightening, which has been associated with increased MACE.9
"Swedish quality registries, including SWEDEHEART, have been utilized by Uppsala Clinical research center (UCR) for a number of groundbreaking cardiovascular clinical trials and it is appropriate that a unique device such as the DynamX device would be evaluated in a large number of patients using its infrastructure,” said Professor James. “We have found the device as easy to deliver as a stent, but with the potential to reduce long-term DES-associated risks and improve upon patient outcomes over time.”
The DynamX Bioadaptor has been shown to improve vessel function1 in several ways. It enables the vessel to accommodate disease progression and achieve positive adaptive remodeling by increasing vessel area and maintaining lumen diameter, which preserves blood flow to the heart. DynamX restores vessel function and allows for normal vessel pulsatility and motion, enabling it to provide more blood flow in response to the body’s needs during physical activity. It also allows the vessel to return to baseline angulation, which may reduce adverse events.
“The INFINITY-SWEDEHEART RCT utilizing the respected SWEDEHEART registry database is an efficient approach to conducting an evidence-based trial, and provides important benefits. For the first time, we will be able to compare the performance of the physiologically-adaptive DynamX against an industry-leading DES in the overall study population and in subsets of patients. In addition, by leveraging the existing rigorous SWEDEHEART registry database, we will be able to conduct the trial and follow-up with high quality, efficiency and speed,” said Motasim Sirhan, Elixir Medical’s CEO.
The DynamX Coronary Bioadaptor System is CE Mark approved. It is not available for sale in the United States.
References
1 Verheye S, Vrolix M, Montorfano M, Zivelonghi C, Giannini F, Bedogni F, et al. Twelve-month clinical and imaging outcomes of the uncaging coronary DynamX Bioadaptor. EuroIntervention 2020;16;e974-e981
2 Iqbal J, Serruys PW, Silber S, et al. Comparison of zotarolimus- and everolimus-eluting coronary stents: final 5-year report of the RESOLUTE all-comers trial. Circ Cardiovasc Interv. 2015;8(6):e002230. doi:10.1161/CIRCINTERVENTIONS.114.002230
3 Kufner S, Joner M, Thannheimer A, Hoppmann P, Ibrahim T, Mayer K, et al. Ten-year clinical outcomes from a trial of three limus-eluting stents with different polymer coatings in patients with coronary artery disease: results from the ISAR-TEST 4 randomized trial. Circulation. 2019; 139:325–333. doi: 10.1161/CIRCULATIONAHA.118.038065.
4 Smits, PC, Valchojannis, GJ, McFadden, EP, et al. Final 5-year follow-up of a randomized controlled trial of everolimus- and paclitaxel-eluting stents for coronary revascularization in daily practice. J Am Coll Cardiol Intv. 2015 Aug, 8 (9) 1157-1165.
5 Stone GW, Kimura T, Gao R, et al. Time-varying outcomes with the Absorb Bioresorbable Vascular Scaffold during 5-year follow-up: a systematic meta-analysis and individual patient data pooled study. JAMA Cardiol. 2019;4(12):1261–1269. doi:10.1001/jamacardio.2019.4101
6 Nakamura M, Yock PG, Bonneau HN, et al. Impact of peri-stent remodeling on restenosis: a volumetric intravascular ultrasound study. Circulation. 2001;103(17):2130-2132. doi:10.1161/01.cir.103.17.2130
7 Maier, W, Windecker, S, Kung, A, et al. Exercise-induced coronary artery vasodilation is not impaired by stent placement. Circulation. 2002; 105(20): 2373-2377. doi: 10.1161/01.cir.0000016360.97819.44
8 Hamilos, M, Sarma, J, Ostojic, M, et al. (2008). Interference of drug-eluting stents with endothelium-dependent coronary vasomotion evidence for device-specific responses. Circ Cardiovasc Interv. 1. 193-200. 10.1161/CIRCINTERVENTIONS.108.797928.
9 Gyöngyösi M, Yang P, Khorsand A, Glogar D. Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events. Austrian Wiktor Stent Study Group and European Paragon Stent Investigators. J Am Coll Cardiol. 2000;35(6):1580-1589. doi:10.1016/s0735-1097(00)00570-2
