COMMENTARY For reprint orders, please contact: [email protected]
Short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO™ dual-therapy stent: what we plan to learn from REDUCE “Acute coronary syndrome often reflects
a degree of damage to the coronaries by atherosclerosis, a progressive process by which plaque (cholesterol) buildup creates a blockage that disrupts blood flow and could potentially rupture.” Harry Suryapranata*,1 & Giuseppe De Luca2 Acute coronary syndrome (ACS) refers to a group of symptoms attributed to obstruction of the coronary artery associated with coronary thrombosis that could lead to life-threatening consequences [1] . Death rates and major cardiovascular events associated with ACS are exceptionally high, with an excess of 2.5 million global cases diagnosed annually [2] . Statistically, one in ten ACS patients will experience repeated major thrombotic events (leading to cardiovascular death, heart attack or stroke) within the first year following the initial incident of ACS [3,4] , of which 68–97% could result in death after hospital discharge [5] . ACS involves ST-segment elevation myocardial infraction (STEMI), non-STEMI (NSTEMI) or unstable angina (UA) [6] . For STEMI and NSTEMI patients, typical symptoms include chest pain at rest, nausea, vomiting, sweating and shortness of breath [7] . Comparing the two, STEMI (accounting for 70% of heart attacks) is more severe as it usually involves completely occluded major coronaries that causes full damage to the heart muscle (ECG ST-elevation),
while NSTEMI (accounting for 30% of heart attacks) involves partial occlusion of coronary arteries, causing only partial damage to the heart muscle (no ECG ST-elevation) [6] . UA involves ischemic chest pain (occurring at rest or with minimal exertion) that becomes increasingly more severe, prolonged or frequent and is caused by an imbalance between oxygen demanded by and oxygen supplied to the heart muscle [6] . The main mechanism is rupture or erosion of an atherosclerotic plaque that triggers platelet aggregation and forms a nonocclusive thrombus that partially obstructs the coronary blood flow, which restricts the amount of oxygen going to the heart muscle, without muscle damage [3] . Symptoms include pain extended from the chest to the neck, jaw, left shoulder, back and left arm; sweating, vomiting or breathing difficulty may also be present [8,9] . ACS often reflects a degree of damage to the coronaries by atherosclerosis, a progressive process by which plaque (cholesterol) buildup creates a blockage that disrupts blood flow and could potentially rupture. If this occurs, it could cause blood to clot inside the artery at
KEYWORDS
• acute coronary syndrome • bleeding risk • drug-eluting stent • dual antiplatelet therapy • safety
Radboud University Medical Center, Nijmegen, The Netherlands Novara Hospital, Novara, Italy *Author for correspondence: [email protected] 1 2
10.2217/FCA.14.81 © 2015 Future Medicine Ltd
part of
Future Cardiol. (2015) 11(1), 17–20
ISSN 1479-6678
17
Commentary Suryapranata & De Luca
“As for the treatment of
anatomical disease, coronary stenting is common practice thanks to groundbreaking innovations and continued advances in stent technology.”
18
the site of the rupture, leading to a heart attack. Primary prevention methods for atherosclerosis are controlling risk factors such as poor diet, lack of exercise, hypertension, hypercholesterolemia, diabetes and smoking. In patients with significant risk factors, aspirin has been shown to reduce the risk of cardiovascular events [10] . In terms of ACS management and treatment, medication by means of single or dual antiplatelet therapy (DAPT) with agents such as aspirin, clopidogrel, prasugrel or ticagrelor, β-blockers or statins are common. For STEMI, primary percutaneous coronary intervention (PCI) is the treatment of choice for the reperfusion or restoration of blood flow, but if the procedure cannot be accessed or achieved within 120 min of diagnosis, thrombolytic therapy is normally given [11] . For NSTEMI and UA, initial drug treatment and clinical stabilization may be appropriate in low-risk patients, followed by coronary angiography and revascularization (PCI for one- or two-vessel disease; coronary artery bypass graft for left main and severe three-vessel disease), which, by contrast, is highly recommended as the initial approach for medium- to high-risk patients. Thrombolytic therapy is not recommended for NSTEMI in order to avoid the risk of reinfarction and unnecessary bleeding complications [12] . Apart from urgent coronary intervention in STEMI, PCI in general is the most effective treatment for ACS patients in terms of symptomatic relief and improved overall patient outcomes [4] . As for the treatment of anatomical disease, coronary stenting is common practice thanks to groundbreaking innovations and continued advances in stent technology. The introduction of first-generation drug-eluting stents (DESs) in 1999 redefined the standard of PCI by providing control over neointimal hyperplasia by inhibiting the proliferation and migration of vascular smooth muscle cells. This resulted in significantly reduced rates of in-stent restenosis, target lesion vascularization [5] and major adverse cardiac events compared with their predecessors, bare metal stents. Despite improved efficacy, however, concerns remain over the association of DESs with stent thrombosis, a seldom but potentially lethal event (by heart attack) caused by platelet aggregation on the stent’s surface and subsequent formation of blood clots. These are caused by delayed healing induced by the same antiproliferative drugs that suppress neointimal hyperplasia. The
Future Cardiol. (2015) 11(1)
predictive risk of stent thrombosis is high, particularly for diabetic patients (with comorbid ities) [6] , and especially for ACS (with high thrombogenicity), requiring longer DAPT after stent implantation for the prevention of stent thrombosis and as secondary prevention of major adverse cardiac events (12 months as per American Heart Association [AHA]–American College of Cardiology [ACC]–Society for Cardiac Angiography and Interventions [SCAI] guidelines on first-generation DESs). Long-term DAPT, however, is not a bulletproof solution due to issues such as patient compliance, as well as the severe and fatal bleeding risks associated with prolonged consumption of DAPT, which have been suggested from recent clinical studies to counterbalance its clinical benefit [13] . Optimal DAPT duration is a highly controversial topic, especially when considering that the current DAPT guidelines are still based on first-generation DESs, and a shift in the paradigm in recent years towards a shorter DAPT duration (3–6 months for non-ACS) after PCI has been witnessed, along with a general peer impression that the old guidelines may no longer comply with the newer-generation DESs. With regards to stent development and advancement in technology, the most recent DESs on the market have adopted safer and more patient-friendly approaches towards vascular treatment by using thinner and bioresorbable polymers for drug delivery in order to reduce vessel inflammation and applying an abluminal drug coating in order to reduce interference on luminal healing. The aim of this approach is to facilitate greater flexibility in DAPT in order to reduce the potential bleeding risks associated with prolonged DAPT, a feature that is increasingly regarded as beneficial to patient care. The COMBO™ (OrbusNeich Inc, FL, USA) dual therapy stent is a new device that combines the antiproliferative effect of conventional DESs and a healing effect via proprietary endothelial progenitor cell (EPC) capture technology to promote vascular repair and vessel regeneration [14] , as well as to potentially reduce DAPT duration and the associated bleeding risks, without increasing thrombotic risks. The feasibility of shortened DAPT using COMBO, however, especially under the setting of ACS, requires further investigation and safety validation in larger-scale randomized clinical trials. The REDUCE trial is a randomized, multicenter study involving 1500 patients that
future science group
What we plan to learn from REDUCE is designed to demonstrate the safety of COMBO with shortened DAPT in ACS patients [15] . REDUCE is a first-of-its-kind study that is specifically targeted at ACS patients treated with a new-generation coronary stent randomly assigned to three versus 12 months of DAPT. If COMBO is able to demonstrate similar safety and clinical outcomes for ACS patients after just 3 months of DAPT, the regimen could be extended to include all patient cohorts, with the potential validation supporting further DAPT reduction in non-ACS patients. The COMBO stent is the world’s first and only dual therapy stent, controlling neointimal proliferation and accelerating endothelial coverage. This facilitates healing and recovery and thus overcomes the main limitations of conventional monotherapy stents (i.e., DESs). Its unique approach to stenting shows excellent early healing benefits and durability over the long-term that are not seen with any current DES [16] . By naturally restoring the vessel, there is a reduced likelihood of future interventions, as it protects against stent thrombus formation, reduces inflammation and promotes normal endothelial function. These differentiating factors demonstrated in the COMBO stent rely on the unique drug-eluting and EPC capture technology, which accelerates natural healing through the promotion of endothelial coverage of the vessel wall after stent implantation [17] . This unique technology consists of an antibody surface coating that captures EPCs circulating in the blood in order to form an endothelial layer. The second component includes an effective dose of sirolimus, which is also eluted from the References 1
MacKay J, Mensah G. Deaths from coronary heart disease. www.who.int
2
Grech ED, Ramsdale DR. Acute coronary syndrome: unstable angine and non-ST segment elevation myocardial infarction. BMJ 326(7401), 1259–1261 (2003).
3
4
Yusuf S, Zhao F, Mehta SR et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 345(7), 494–502 (2001). Mega JL, Braunwald E, Wiviot SD et al. Rivaroxaban in patients with a recent acute coronary syndrome. N. Engl. J. Med. 366(1), 9–19 (2012).
abluminal side of the stent into the tissue for control of neointimal proliferation. In fact, the stent struts have been shown to be covered by endothelial cells by as early as 50 days [16] . For this reason, the COMBO stent demonstrates good potential for reducing dependency on DAPT and, consequently, avoids the risks associated with DAPT discontinuation and lowers the risks of bleeding and subsequent complications. The global burden of ACS is massive, affecting 2.5 million people globally, yet little is known about the optimal duration of DAPT among the subgroup of patients who have undergone PCI. It is clear that the current recommended 12-month duration of DAPT is unsatisfactory due to the side effects of bleeding, especially with new stronger antiplatelet compounds such as prasugrel and ticagrelor, and the threat of the need for DAPT disruption. While the optimal DAPT duration remains under debate, COMBO, as studied in the REDUCE trial, could provide valuable insights into potentially redefining the safety guidelines for reducing DAPT duration in the near future.
vessel, there is a reduced likelihood of future interventions, as it protects against stent thrombus formation, reduces inflammation and promotes normal endothelial function.”
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. Fox KA, Carruthers KF, Dunbar DR et al. Underestimated and under-recognised: the late consequences of acute coronary syndrome (GRACE UK–Belgian Study). Eur. Heart J. 31(22), 2755–2764 (2010).
6
Overbaugh KJ. Acute coronary syndrome. Am. J. Nurs. 109(5), 42–52 (2009).
7
American Heart Association. Acute coronary syndrome. www.heart.org
8
WebMD. Heart attack and unstable angina – symptoms. www.webmd.com British Cardiac Patients Association. Angina factsheet. www.bcpa.co.uk/factsheets/Angina.htm
10 Baigent C, Blackwell L, Collins R et al.
Aspirin in the primary and secondary
future science group
“By naturally restoring the
Financial & competing interests disclosure
5
9
Commentary
prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet 373(9678) 1849–1860 (2009). 11 O’Gara PT, Kushner FG, Ascheim DD et al.
ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 61(4), e78–e140 (2013). 12 Gershlick AH, Stephens-Lloyd A, Hughes A
et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N. Engl. J. Med. 353(26), 2758–2768 (2005). 13 De Luca G, Dirksen MT, Spaulding C et al.
Time, course, predictors and clinical
www.futuremedicine.com
19
Commentary Suryapranata & De Luca implications of stent thrombosis following primary angioplasty. Insights from the DESERT cooperation. Thromb. Haemost. 110(4), 826–833 (2013). 14 Cardiology’s Today’s Intervention.
Dual-therapy stenting: the next step in the evolution of stent design. www.healio.com
20
15 ClinicalTrials.gov. Short-term Dual Anti
Platelet Therapy in Patients With ACS Treated With the COMBO Dual-therapy Stent (REDUCE). www.clinicaltrials.gov 16 Luen Lee S, Lam SC, Kong S et al.
TCT-367 2-year sequential OCT follow-up findings and 3-year clinical outcomes of the new dual therapy endothelial progenitor cell capturing sirolimus-eluting COMBO stent:
Future Cardiol. (2015) 11(1)
the EGO-COMBO study. J. Am. Coll. Cardiol. doi:10.1016/j.jacc.2014.07.415 (2014) (Epub ahead of print). 17 Granada Juan F, Shigenobu I, Aboodi M
et al. Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix. Circ. Cardiovasc. Interv. 3, 257–266 (2010).
future science group
Short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO™ dual-therapy stent: what we plan to learn from REDUCE “Acute coronary syndrome often reflects
a degree of damage to the coronaries by atherosclerosis, a progressive process by which plaque (cholesterol) buildup creates a blockage that disrupts blood flow and could potentially rupture.” Harry Suryapranata*,1 & Giuseppe De Luca2 Acute coronary syndrome (ACS) refers to a group of symptoms attributed to obstruction of the coronary artery associated with coronary thrombosis that could lead to life-threatening consequences [1] . Death rates and major cardiovascular events associated with ACS are exceptionally high, with an excess of 2.5 million global cases diagnosed annually [2] . Statistically, one in ten ACS patients will experience repeated major thrombotic events (leading to cardiovascular death, heart attack or stroke) within the first year following the initial incident of ACS [3,4] , of which 68–97% could result in death after hospital discharge [5] . ACS involves ST-segment elevation myocardial infraction (STEMI), non-STEMI (NSTEMI) or unstable angina (UA) [6] . For STEMI and NSTEMI patients, typical symptoms include chest pain at rest, nausea, vomiting, sweating and shortness of breath [7] . Comparing the two, STEMI (accounting for 70% of heart attacks) is more severe as it usually involves completely occluded major coronaries that causes full damage to the heart muscle (ECG ST-elevation),
while NSTEMI (accounting for 30% of heart attacks) involves partial occlusion of coronary arteries, causing only partial damage to the heart muscle (no ECG ST-elevation) [6] . UA involves ischemic chest pain (occurring at rest or with minimal exertion) that becomes increasingly more severe, prolonged or frequent and is caused by an imbalance between oxygen demanded by and oxygen supplied to the heart muscle [6] . The main mechanism is rupture or erosion of an atherosclerotic plaque that triggers platelet aggregation and forms a nonocclusive thrombus that partially obstructs the coronary blood flow, which restricts the amount of oxygen going to the heart muscle, without muscle damage [3] . Symptoms include pain extended from the chest to the neck, jaw, left shoulder, back and left arm; sweating, vomiting or breathing difficulty may also be present [8,9] . ACS often reflects a degree of damage to the coronaries by atherosclerosis, a progressive process by which plaque (cholesterol) buildup creates a blockage that disrupts blood flow and could potentially rupture. If this occurs, it could cause blood to clot inside the artery at
KEYWORDS
• acute coronary syndrome • bleeding risk • drug-eluting stent • dual antiplatelet therapy • safety
Radboud University Medical Center, Nijmegen, The Netherlands Novara Hospital, Novara, Italy *Author for correspondence: [email protected] 1 2
10.2217/FCA.14.81 © 2015 Future Medicine Ltd
part of
Future Cardiol. (2015) 11(1), 17–20
ISSN 1479-6678
17
Commentary Suryapranata & De Luca
“As for the treatment of
anatomical disease, coronary stenting is common practice thanks to groundbreaking innovations and continued advances in stent technology.”
18
the site of the rupture, leading to a heart attack. Primary prevention methods for atherosclerosis are controlling risk factors such as poor diet, lack of exercise, hypertension, hypercholesterolemia, diabetes and smoking. In patients with significant risk factors, aspirin has been shown to reduce the risk of cardiovascular events [10] . In terms of ACS management and treatment, medication by means of single or dual antiplatelet therapy (DAPT) with agents such as aspirin, clopidogrel, prasugrel or ticagrelor, β-blockers or statins are common. For STEMI, primary percutaneous coronary intervention (PCI) is the treatment of choice for the reperfusion or restoration of blood flow, but if the procedure cannot be accessed or achieved within 120 min of diagnosis, thrombolytic therapy is normally given [11] . For NSTEMI and UA, initial drug treatment and clinical stabilization may be appropriate in low-risk patients, followed by coronary angiography and revascularization (PCI for one- or two-vessel disease; coronary artery bypass graft for left main and severe three-vessel disease), which, by contrast, is highly recommended as the initial approach for medium- to high-risk patients. Thrombolytic therapy is not recommended for NSTEMI in order to avoid the risk of reinfarction and unnecessary bleeding complications [12] . Apart from urgent coronary intervention in STEMI, PCI in general is the most effective treatment for ACS patients in terms of symptomatic relief and improved overall patient outcomes [4] . As for the treatment of anatomical disease, coronary stenting is common practice thanks to groundbreaking innovations and continued advances in stent technology. The introduction of first-generation drug-eluting stents (DESs) in 1999 redefined the standard of PCI by providing control over neointimal hyperplasia by inhibiting the proliferation and migration of vascular smooth muscle cells. This resulted in significantly reduced rates of in-stent restenosis, target lesion vascularization [5] and major adverse cardiac events compared with their predecessors, bare metal stents. Despite improved efficacy, however, concerns remain over the association of DESs with stent thrombosis, a seldom but potentially lethal event (by heart attack) caused by platelet aggregation on the stent’s surface and subsequent formation of blood clots. These are caused by delayed healing induced by the same antiproliferative drugs that suppress neointimal hyperplasia. The
Future Cardiol. (2015) 11(1)
predictive risk of stent thrombosis is high, particularly for diabetic patients (with comorbid ities) [6] , and especially for ACS (with high thrombogenicity), requiring longer DAPT after stent implantation for the prevention of stent thrombosis and as secondary prevention of major adverse cardiac events (12 months as per American Heart Association [AHA]–American College of Cardiology [ACC]–Society for Cardiac Angiography and Interventions [SCAI] guidelines on first-generation DESs). Long-term DAPT, however, is not a bulletproof solution due to issues such as patient compliance, as well as the severe and fatal bleeding risks associated with prolonged consumption of DAPT, which have been suggested from recent clinical studies to counterbalance its clinical benefit [13] . Optimal DAPT duration is a highly controversial topic, especially when considering that the current DAPT guidelines are still based on first-generation DESs, and a shift in the paradigm in recent years towards a shorter DAPT duration (3–6 months for non-ACS) after PCI has been witnessed, along with a general peer impression that the old guidelines may no longer comply with the newer-generation DESs. With regards to stent development and advancement in technology, the most recent DESs on the market have adopted safer and more patient-friendly approaches towards vascular treatment by using thinner and bioresorbable polymers for drug delivery in order to reduce vessel inflammation and applying an abluminal drug coating in order to reduce interference on luminal healing. The aim of this approach is to facilitate greater flexibility in DAPT in order to reduce the potential bleeding risks associated with prolonged DAPT, a feature that is increasingly regarded as beneficial to patient care. The COMBO™ (OrbusNeich Inc, FL, USA) dual therapy stent is a new device that combines the antiproliferative effect of conventional DESs and a healing effect via proprietary endothelial progenitor cell (EPC) capture technology to promote vascular repair and vessel regeneration [14] , as well as to potentially reduce DAPT duration and the associated bleeding risks, without increasing thrombotic risks. The feasibility of shortened DAPT using COMBO, however, especially under the setting of ACS, requires further investigation and safety validation in larger-scale randomized clinical trials. The REDUCE trial is a randomized, multicenter study involving 1500 patients that
future science group
What we plan to learn from REDUCE is designed to demonstrate the safety of COMBO with shortened DAPT in ACS patients [15] . REDUCE is a first-of-its-kind study that is specifically targeted at ACS patients treated with a new-generation coronary stent randomly assigned to three versus 12 months of DAPT. If COMBO is able to demonstrate similar safety and clinical outcomes for ACS patients after just 3 months of DAPT, the regimen could be extended to include all patient cohorts, with the potential validation supporting further DAPT reduction in non-ACS patients. The COMBO stent is the world’s first and only dual therapy stent, controlling neointimal proliferation and accelerating endothelial coverage. This facilitates healing and recovery and thus overcomes the main limitations of conventional monotherapy stents (i.e., DESs). Its unique approach to stenting shows excellent early healing benefits and durability over the long-term that are not seen with any current DES [16] . By naturally restoring the vessel, there is a reduced likelihood of future interventions, as it protects against stent thrombus formation, reduces inflammation and promotes normal endothelial function. These differentiating factors demonstrated in the COMBO stent rely on the unique drug-eluting and EPC capture technology, which accelerates natural healing through the promotion of endothelial coverage of the vessel wall after stent implantation [17] . This unique technology consists of an antibody surface coating that captures EPCs circulating in the blood in order to form an endothelial layer. The second component includes an effective dose of sirolimus, which is also eluted from the References 1
MacKay J, Mensah G. Deaths from coronary heart disease. www.who.int
2
Grech ED, Ramsdale DR. Acute coronary syndrome: unstable angine and non-ST segment elevation myocardial infarction. BMJ 326(7401), 1259–1261 (2003).
3
4
Yusuf S, Zhao F, Mehta SR et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 345(7), 494–502 (2001). Mega JL, Braunwald E, Wiviot SD et al. Rivaroxaban in patients with a recent acute coronary syndrome. N. Engl. J. Med. 366(1), 9–19 (2012).
abluminal side of the stent into the tissue for control of neointimal proliferation. In fact, the stent struts have been shown to be covered by endothelial cells by as early as 50 days [16] . For this reason, the COMBO stent demonstrates good potential for reducing dependency on DAPT and, consequently, avoids the risks associated with DAPT discontinuation and lowers the risks of bleeding and subsequent complications. The global burden of ACS is massive, affecting 2.5 million people globally, yet little is known about the optimal duration of DAPT among the subgroup of patients who have undergone PCI. It is clear that the current recommended 12-month duration of DAPT is unsatisfactory due to the side effects of bleeding, especially with new stronger antiplatelet compounds such as prasugrel and ticagrelor, and the threat of the need for DAPT disruption. While the optimal DAPT duration remains under debate, COMBO, as studied in the REDUCE trial, could provide valuable insights into potentially redefining the safety guidelines for reducing DAPT duration in the near future.
vessel, there is a reduced likelihood of future interventions, as it protects against stent thrombus formation, reduces inflammation and promotes normal endothelial function.”
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. Fox KA, Carruthers KF, Dunbar DR et al. Underestimated and under-recognised: the late consequences of acute coronary syndrome (GRACE UK–Belgian Study). Eur. Heart J. 31(22), 2755–2764 (2010).
6
Overbaugh KJ. Acute coronary syndrome. Am. J. Nurs. 109(5), 42–52 (2009).
7
American Heart Association. Acute coronary syndrome. www.heart.org
8
WebMD. Heart attack and unstable angina – symptoms. www.webmd.com British Cardiac Patients Association. Angina factsheet. www.bcpa.co.uk/factsheets/Angina.htm
10 Baigent C, Blackwell L, Collins R et al.
Aspirin in the primary and secondary
future science group
“By naturally restoring the
Financial & competing interests disclosure
5
9
Commentary
prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet 373(9678) 1849–1860 (2009). 11 O’Gara PT, Kushner FG, Ascheim DD et al.
ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 61(4), e78–e140 (2013). 12 Gershlick AH, Stephens-Lloyd A, Hughes A
et al. Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. N. Engl. J. Med. 353(26), 2758–2768 (2005). 13 De Luca G, Dirksen MT, Spaulding C et al.
Time, course, predictors and clinical
www.futuremedicine.com
19
Commentary Suryapranata & De Luca implications of stent thrombosis following primary angioplasty. Insights from the DESERT cooperation. Thromb. Haemost. 110(4), 826–833 (2013). 14 Cardiology’s Today’s Intervention.
Dual-therapy stenting: the next step in the evolution of stent design. www.healio.com
20
15 ClinicalTrials.gov. Short-term Dual Anti
Platelet Therapy in Patients With ACS Treated With the COMBO Dual-therapy Stent (REDUCE). www.clinicaltrials.gov 16 Luen Lee S, Lam SC, Kong S et al.
TCT-367 2-year sequential OCT follow-up findings and 3-year clinical outcomes of the new dual therapy endothelial progenitor cell capturing sirolimus-eluting COMBO stent:
Future Cardiol. (2015) 11(1)
the EGO-COMBO study. J. Am. Coll. Cardiol. doi:10.1016/j.jacc.2014.07.415 (2014) (Epub ahead of print). 17 Granada Juan F, Shigenobu I, Aboodi M
et al. Development of a novel prohealing stent designed to deliver sirolimus from a biodegradable abluminal matrix. Circ. Cardiovasc. Interv. 3, 257–266 (2010).
future science group
