Inhibition of Orai1-mediated Ca(2+) entry is a key mechanism of the antiproliferative action of sirolimus in human arterial smooth muscle.

Sirolimus (rapamycin) is used in drug-eluting stent strategies and proved clearly superior in this application compared with other immunomodulators such as pimecrolimus. The molecular basis of this action of sirolimus in the vascular system is still incompletely understood. Measurements of cell proliferation in human coronary artery smooth muscle cells (hCASM) demonstrated a higher antiproliferative activity of sirolimus compared with pimecrolimus. Although sirolimus lacks inhibitory effects on calcineurin, nuclear factor of activated T-cell activation in hCASM was suppressed to a similar extent by both drugs at 10 µM. Sirolimus, but not pimecrolimus, inhibited agonist-induced and store-operated Ca(2+) entry as well as cAMP response element binding protein (CREB) phosphorylation in human arterial smooth muscle, suggesting the existence of an as-yet unrecognized inhibitory effect of sirolimus on Ca(2+) signaling and Ca(2+)-dependent gene transcription. Electrophysiological experiments revealed that only sirolimus but not pimecrolimus significantly blocked the classical stromal interaction molecule/Orai-mediated, store-operated Ca(2+) current reconstituted in human embryonic kidney cells (HEK293). A link between Orai function and proliferation was confirmed by dominant-negative knockout of Orai in hCASM. Analysis of the effects of sirolimus on cell proliferation and CREB activation in an in vitro model of arterial intervention using human aorta corroborated the ability of sirolimus to suppress stent implantation-induced CREB activation in human arteries. We suggest inhibition of store-operated Ca(2+) entry based on Orai channels and the resulting suppression of Ca(2+) transcription coupling as a key mechanism underlying the antiproliferative activity of sirolimus in human arteries. This mechanism of action is specific for sirolimus and not a general feature of drugs interacting with FK506-binding proteins.

A TRPC3 blocker, ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3), prevents stent-induced arterial remodeling.

TRPC-mediated Ca(2+) entry has been implicated in the control of smooth muscle proliferation and might represent a pivotal mechanism underlying in-stent restenosis. As we have observed significant expression of TRPC3 in human smooth muscle from the coronary artery as well as the aorta, we tested the efficiency of a recently discovered TRPC3 selective Ca(2+) entry blocker Pyr3 to prevent vascular smooth muscle proliferation and stent implantation-induced hyperplasia of human aorta. The effect of Pyr3 on proliferation was measured by detection of BrdU incorporation and PCNA expression in human coronary smooth muscle and microvascular endothelium, which displays significantly smaller expression levels of TRPC3 as compared with smooth muscle. Pyr3 inhibited smooth muscle proliferation but lacked detectable effects on endothelial proliferation. Measurements of ATP-induced Ca(2+) signals revealed that Pyr3 suppressed agonist-induced Ca(2+) entry more effectively in vascular smooth muscle than in endothelial cells. Inhibitory effects of Pyr3 on stent implantation-induced arterial injury was tested using a novel in vitro model of in-stent hyperplasia in human arteries based on organ typical culture of human aortic constructs. Pyr3 effectively prevented increases in tissue levels of PCNA and Ki-67 at 2 weeks after stent implantation into human aortae. Similarly, proliferation markers were significantly suppressed when implanting a Pyr3-releasing stent prototype as compared with a bare metal stent (BMS) control. Our results suggest TRPC3 as a potential target for pharmacological control of smooth muscle proliferation. Selectively inhibition of TRPC Ca(2+) entry channels in vascular smooth muscle is suggested as a promising strategy for in-stent restenosis prevention.

In vitro and in vivo evaluation of a novel bioresorbable magnesium scaffold with different surface modifications.

The novel Resoloy® rare earth magnesium alloy was developed for bioresorbable vascular implant application, as an alternative to the WE43 used in Biotronik's Magmaris scaffold, which received CE approval in 2016. Initially, the Magmaris showed very promising preclinical and clinical results, but the formation of an unexpected conversion product and a too fast loss of integrity has proven to be a flaw. The safety and efficacy of Resoloy, which is intended to be bioresorbed without any remnants, has been investigated in an in vitro degradation study and a porcine coronary animal model. Four different groups of scaffolds composed of Resoloy (Res) as the backbone material and additionally equipped with a fluoride passivation layer (Res-F), a polyester topcoat (Res-P), or a duplex layer composed of a fluoride passivation layer and a polymeric topcoat (Res-PF) were compared to a Magmaris scaffold in an in vitro degradation test. Preclinical safety and efficacy of Res-F and Res-PF were subsequently evaluated in a coronary porcine model for 12 and 28 days. Scanning electron microscope, quantitative coronary angiography, micro-computed tomography, histopathology, and histomorphometry analyses were conducted to evaluate preclinical parameters and degradation behavior of the scaffolds. Res-PF with a duplex layer shows the slowest degradation and the longest supporting force of all test groups. The in vitro data are confirmed by the results of the in vivo study, in which Res-PF exhibited a longer supporting force than Res-F, but also caused higher neointima formation. Both studied groups showed excellent biocompatibility. A starter colonization of the strut area with cells during bioresorption was observed. The in vitro degradation test shows that a combination of MgF2 passivation and a PLLA topcoat on a Resoloy magnesium backbone (Res-PF) leads to a much slower degradation and a longer support time than a Magmaris control group. In a preclinical study, the safety and efficacy of this duplex layer could be demonstrated. The beginning colonization of the degraded strut area by macrophages can be seen as clear indications that the resorption of the intermediate degradation product takes a different course than that of the Magmaris scaffold.

Preclinical evaluation of degradation kinetics and elemental mapping of first- and second-generation bioresorbable magnesium scaffolds.

AIMS: Because vascular restoration therapy using bioresorbable vascular scaffolds (BRS) remains an appealing concept to restore vasoreactivity, an understanding of biodegradation remains paramount during preclinical testing. We therefore aimed to investigate the qualitative and temporal course of degradation of magnesium alloy-based bioresorbable vascular scaffolds in juvenile swine. METHODS AND RESULTS: Qualitative characterisation of biodegradation was performed in 41 DREAMS 1G up to three years, while degradation kinetics were acquired in 54 DREAMS 2G implanted into porcine coronary arteries for 28, 90 and 180 days, one and two years. Assessment of end product composition was achieved in DREAMS 2G at 180 days. Myocardium was examined, while an OCT attenuation score was derived at strut level from 180 days to two years in DREAMS 2G. Degradation of DREAMS entails two corrosive phases. At one year, 94.8% of the magnesium was bioabsorbed in DREAMS 2G and, at two years, magnesium was completely replaced by amorphous calcium phosphate. Von Kossa staining revealed variable peri-strut mineralisation at all time points and only small focal myocardial emboli observed in one animal in the 180 days cohort. Strut discontinuity density was low at 28 days (0.5±0.57 per mm) and increased to a density above 7.5 per mm up to one year. OCT attenuation score correlated well with strut-based degradation analysis up to two years. CONCLUSIONS: While the current set of data supports vascular safety, clinical trials are warranted to prove the concept of vascular restoration following DREAMS implantation.

Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries.

OBJECTIVE: We aimed to evaluate an effective dosage and safety profile of pimecrolimus as an anti-inflammatory drug for drug-eluting stents. METHODS: In the dose finding study, coronary arteries of 20 domestic swine were randomly implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and 120 microg) over a period of 4 weeks. In addition, pimecrolimus (75 microg) and ProKinetic stents were randomly implanted into six swine over 3 months. In the safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45 microg) and high-dose pimecrolimus (120 microg), and overlapping mid-dose stents were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and ProKinetic stent with PLLA were implanted over a period of 3 months. RESULTS: The dose finding study revealed excellent luminal patency with low percent occlusion (approximately 29% vs. approximately 41%), injury (0.53-0.59 vs. 1.25), and inflammation (0.78-0.97 vs. 1.08) for the pimecrolimus group compared with the vision group. The safety study arm showed similar angiographic results for all tested groups, with a significantly larger minimal lumen diameter for pimecrolimus stents compared to PLLA stents. Except for the high-dose group and overlapping area of the overlapping group, promising morphometric results were found for pimecrolimus compared to bare metal stents. CONCLUSIONS: Present data suggest that pimecrolimus-eluting stents are safe and have a similar healing profile to bare metal stents. They may suppress inflammation, leading to a reduced intimal response and a milder inflammatory reaction in a porcine model.

Still room for improvement: Preclinical and bench testing of a thin-strut cobalt-chromium bare-metal stent with passive coating.

There is a renewed interest in bare-metal stent (BMS) design as degradable polymer coatings are increasingly used as drug-delivery vehicles in drug-eluting stents (DESs), leaving it to the BMS platform to determine the long-term outcome of DES treatment. In this study comprising preclinical and bench tests, we compare two modern thin-strut BMSs of different design. Angiography, morphometry, and histopathology data were acquired in a porcine coronary artery model in a 28-day single-stent study (13 hybrid farm pigs) and in a 90-day overlapping-stent study (8 Yucatan mini-pigs). Standardized bench tests including ion release test were performed to compare mechanical performance of the two stent systems. We found that the optimized stent group induced significantly less neointimal formation and less inflammation than Multi-Link Vision in both (single stent and overlapping stent) porcine studies. The higher efficacy was also associated with a markedly reduced release of cobalt, nickel, chromium, and tungsten ions in physiological solution and better performance in mechanical delivery tests. In conclusion, a further increase in efficacy and better safety profile than the well-known Multi-Link Vision BMS can be achieved by careful optimization of the BMS backbone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1612-1621, 2017.

Second-generation magnesium scaffold Magmaris: device design and preclinical evaluation in a porcine coronary artery model.

AIMS: The second-generation drug-eluting absorbable magnesium scaffold Magmaris, recently introduced for the treatment of obstructive coronary atherosclerotic lesions, suggests a good safety profile, but preclinical assessment is important for predicting clinical performance. The aim of the present study was to assess subacute and long-term safety as well as pharmacokinetic properties of the Magmaris compared with a current-generation metallic DES and an approved BRS in porcine and rabbit animal models. METHODS AND RESULTS: Ninety Magmaris scaffolds were implanted into non-diseased porcine and rabbit models. A bioresorbable vascular scaffold (Absorb) and a permanent drug-eluting stent (XIENCE Xpedition) served as controls. Scanning electron microscopy showed increased endothelialisation and decreased thrombus formation at three and 28 days in the Magmaris group compared with the Absorb group. In the XIENCE group, inflammation exceeded the level in the Magmaris group at 365 and 730 days. Neointimal growth was greater in the Magmaris group than in the XIENCE group. Late lumen loss decreased over time in both groups. Optical coherence tomography (OCT) showed stable luminal dimensions in both the Magmaris and XIENCE groups. Pharmacokinetic studies demonstrated a retarded elution profile in the Magmaris group with 69.4% of sirolimus released at 90 days. CONCLUSIONS: Preclinical results suggest that the Magmaris has a favourable safety profile with advanced healing relative to benchmark, low acute thrombogenicity, and absence of excessive lumen loss up to two years. These results support clinical application of Magmaris for human use.

Permanent and biodegradable polymer coatings in the absence of antiproliferative drugs in a porcine model of coronary artery stenting.

AIMS: The purpose of the present study was to examine the comparative vascular healing response to stents coated with permanent or biodegradable polymer and uncoated stents in a porcine model of coronary artery stenting. METHODS AND RESULTS: Juvenile pigs were randomly allocated to implantation of stents coated with permanent polymer (PP, methacrylate-based, n=10), biodegradable polymer (BP, poly-lactic acid-based, n=10) or bare metal control stents (n=10), in the absence of antiproliferative drugs. At 28 days, animals were sacrificed and specimens prepared for histopathologic assessment. Endothelialisation was complete in all treatment groups. Vascular injury at 28 days was greater in PP stents as compared with uncoated stents (p=0.05) though not as compared with BP-coated stents (p=ns). PP stents showed increased inflammatory scores compared with BP-coated (p=0.03) and uncoated stents (p=0.02). There was also greater neointimal growth with PP-coated stents compared with uncoated stents (p=0.02). CONCLUSIONS: In the absence of antiproliferative drugs, stents coated with methacrylate-based PP, but not with poly-lactic acid-based BP, provoked significant vessel wall inflammatory reactions resulting in greater vascular injury and increased neointimal growth compared with uncoated stents. Biodegradable polymer coatings may be considered preferable to facilitate drug elution with minimal vessel wall toxicity.

Thrombogenicity and early vascular healing response in metallic biodegradable polymer-based and fully bioabsorbable drug-eluting stents.

BACKGROUND: Acute thrombogenicity and re-endothelialization represent clinically relevant end points pertaining to the safety of coronary stents, which have not been compared among biodegradable polymer-based drug-eluting metallic stents and fully bioabsorbable scaffolds to date. METHODS AND RESULTS: We investigated comparative outcomes with respect to acute thrombogenicity and re-endothelialization among thin-strut biodegradable polymer metallic everolimus eluting stents (EES), thick-strut fully bioabsorbable EES, thick-strut biodegradable polymer metallic biolimus-eluting stents and control bare metal stents. An ex-vivo porcine arterio-venous shunt model was used to assess platelet aggregation, whereas a healthy rabbit model of iliofemoral stent implantation was used to assess re-endothelialization and inflammation. Confocal microscopy was used to detect fluorescently labeled antibody staining directed against CD61/CD42b for the identification of aggregated thrombocytes, CD14/PM-1, and RAM-11 for identification of neutrophils and monocytes/macrophages. Endothelial recovery was assessed by scanning electron microscopy, whereas CD31/PECAM-1 was used to confirm endothelial maturity. EES demonstrated significantly less acute thrombogenicity compared with bioabsorbable EES and biolimus-eluting stents. EES showed greater re-endothelialization at 28 days and reduced inflammatory cell adhesion of monocytes/macrophages at 14 days compared with bioabsorbable EES. Only bare metal stents showed complete re-endothelialization at 28 days. CONCLUSIONS: These outcomes indicate differential trends in thrombogenicity and vascular healing among contemporary stents used in clinical practice and suggest a need for long-term adjunct antithrombotic pharmacotherapy for bioabsorbable EES.

Pathological aspects of bioresorbable stent implantation.

The treatment of obstructive coronary artery disease has been revolutionised by the advent of drug-eluting stent therapy. However, concerns remain about complications late after stent implantation including late stent thrombosis, hypersensitivity reactions and neoatherosclerosis. In this respect, the introduction of fully bioresorbable stents (BRS)--which resorb over time and leave the arterial wall free of any metal constraints--represents a potentially important disruptive technology. However, although the concept is intuitively attractive, a thorough understanding of the histopathological changes seen after BRS implantation and an appreciation of comparative changes versus existing metal stent technologies are vital to guide BRS clinical usage. In this respect, translational investigation of polymer chemistry, biomedical engineering, as well as in vitro and in vivo testing in animal models is an important undertaking. This article will review the pathological aspects of BRS implantation with a focus on acute and chronic vascular reactions derived from preclinical animal studies, including insights from in vivo imaging. Finally, potential future directions of this novel therapeutic approach will be discussed.

Bioresorbable drug-eluting magnesium-alloy scaffold: design and feasibility in a porcine coronary model.

AIMS: Among three versions of bioresorbable magnesium scaffolds featuring different paclitaxel-elution kinetics, we determined the best-performing scaffold and compared it with established, paclitaxel-eluting, permanent stents TAXUS Liberté and eucaTAX. METHODS AND RESULTS: Drug-elution kinetics in magnesium scaffolds were modulated by varying the composition of their bioresorbable poly(lactide-co-glycolide) coating loaded with paclitaxel. A 50:50 ratio of lactide to glycolide, or an 85:15 ratio and either high- or low-molecular-weight polymer was applied in the "50/50", "85/15H", and "85/15L" scaffolds, respectively. Seventy-three magnesium scaffolds (25 50/50, 24 85/15H, 24 85/15L) and 36 control stents (18 TAXUS Liberté, 18 eucaTAX) were implanted in coronary arteries of 50 Yucatan mini-pigs. Angiography, histomorphometry, and histopathology data were acquired at 28, 90 and 180 days. The best-performing magnesium scaffold, 85/15H, was equivalent to TAXUS Liberté and superior to eucaTAX regarding late luminal loss, intimal area, fibrin score, and endothelialisation. Intimal inflammation score was higher in 85/15H than in the control stents at 28 days, but this effect disappeared at later time points. CONCLUSIONS: By selecting suitable paclitaxel-elution kinetics, it was feasible to develop a bioresorbable magnesium scaffold whose efficacy and healing characteristics in a porcine coronary model are comparable with those of established paclitaxel-eluting permanent metallic stents.

Preclinical evaluation of a novel drug-eluting balloon in an animal model of in-stent stenosis.

Despite advances in contemporary stent technology, in-stent restenosis (ISR) remains the major limitation following revascularization procedures. We developed a porcine model of ISR to specifically investigate the preclinical outcomes of a novel drug-eluting balloon (DEB) in this particular setting. Fifteen pigs received bare metal stents in each of the major coronary arteries for 28 days to induce neointimal growth. Following repeat angiography, animals were allocated to fourdifferent treatment groups. The control group consisted of a bare angioplasty catheter, while the Pantera Lux™ (3.0 µg/mm(2) paclitaxel) (30 s inflation) was compared to two consecutive deployments of the Pantera Lux™ (60 s inflation each) and the commercial SeQuent(®) Please balloon (60 s inflation). Twenty-eight days following balloon deployment, the animals underwent repeat angiography and were subsequently sacrificed for histopathologic assessment. There was a trend in reduction of percent diameter stenosis in the DEB group versus control (13.9% vs. 20.4%), while longer inflation duration or consecutive DEB deployment had no additional growth-limiting effect. Neointimal thickness was reduced from 0.38 ± 0.13 to 0.30 ± 0.09 mm in the control versus DEB group. All DEB groups showed delayed vascular healing characterized by dose-dependent increases in fibrin deposition and neointimal cell vacuity. Investigation of DEB in a porcine model of ISR is feasible and more accurately represents human disease conditions. The magnitude of neointima suppression is lower than that observed in non-diseased animal models and is accompanied by delayed vascular healing.

Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation.

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher™) at 28, 90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher™ at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drug-eluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher™ may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients.

AIMS: The vascular effects of drug- eluting balloon (DEB) deployment in the absence of coronary stents have not been characterised. This study evaluated potential vascular effects of paclitaxel-coated angioplasty balloons using different excipients in the absence of additional stents. METHODS AND RESULTS: A total 45 porcine arteries were treated with paclitaxel-coated DEBs using four different excipients (all 3.0 µg/mm2): A) iopromide (n=9), B) ATEC excipient (n=8), C) BTHC excipient (n=10), D) lecithine excipient (n=10). Uncoated bare angioplasty balloons served as controls (n=8). Histology, histomorphometry, and quantitative angiography analysis were performed 28 days following intervention. Tissue concentrations of paclitaxel were measured in selected animals using BTHC excipient (n=39 arteries) and reached maximum concentrations of 165 ng/mg 30 min after delivery in coronary target tissue. There were no differences in efficacy endpoints using histomorphology or quantitative angiography between groups. In contrast, however, treatment with DEBs using BTHC excipient or iopromide was associated with increased fibrin deposition and inflammation indicating delayed vascular healing. DEBs using lecithin excipient or uncoated angioplasty balloons did not induce any comparable vascular effects. CONCLUSIONS: Effective excipients are necessary to accomplish successful balloon facilitated paclitaxel delivery, which is associated with delayed vascular healing as a sign of successful drug transfer. The potential of DEBs to diminish restenosis following angioplasty may be insufficient in the absence of additional stents.

Efficacy and safety of absorbable metallic stents with adjunct intracoronary beta radiation in porcine coronary arteries.

BACKGROUND: Absorbable metallic stents (AMS) utilizing Mg alloy carry advantages over permanent metallic stents because of their potential to eliminate stent thrombosis, chronic inflammation, or artifacts with noninvasive imaging. These stents, however, are associated with a modest degree of late recoil and intimal hyperplasia. The aim of the study was to test whether adjunct vascular brachytherapy (VBT) compared to AMS alone can overcome these limitations. METHODS: Juvenile domestic pig coronary arteries underwent implantation of either AMS (n = 11) with prior adjunct VBT utilizing Sr/Y-90 beta source seeds, with a dose of 24 Gy at 2 mm from the source, or AMS alone (n = 11). At 28 days following intravascular ultrasound, vessels were harvested and analyzed by histomorphometry. RESULTS: Intravascular ultrasound analysis indicated that at follow-up, though statistically not significant, lumen and stent areas in the segments deployed with AMS following radiation were larger than those deployed with AMS alone (3.94 +/- 1.38 and 3.53 +/- 1.75 vs. 2.99 +/- 1.05 and 3.58 +/- 1.48). Extrastent plaque and intrastent plaque areas in the same segments were smaller (2.76 +/- 0.82 and 0.24 +/- 0.47 vs. 3.25 +/- 1.94 and 0.58 +/- 0.81). Morphometric data indicate that vessels in the VBT + AMS group showed characteristics of delayed healing and re-endothelialization. Neointimal area was significantly lower in the VBT + AMS group (0.49 +/- 0.34) compared to AMS (1.3 +/- 0.62, P = 0.001). Lumen area of the VBT + AMS was larger when compared with AMS alone (2.49 +/- 0.82 vs. 1.75 +/- 0.51, P = 0.02). CONCLUSION: VBT as an adjunct to AMS further reduces the intimal hyperplasia and improves the lumen area when compared to AMS alone but does not have any impact on late recoil.

Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries.

OBJECTIVE: We aimed to determine the safety and efficacy of biobasorbable magnesium alloy stents in porcine coronary arteries. Bioabsorbable magnesium stents carry the potential to overcome the limitations posed by permanent metallic stents such as chronic inflammation, late stent thrombosis, prolonged antiplatelet therapy, and artifacts when imaged by multislice-computed tomography or magnetic resonance imaging. METHODS: Magnesium alloy stents or stainless steel stents were randomly deployed in coronary arteries of domestic or minipigs. Domestic pigs were sacrificed at 3 days (n = 2) or 28 days, and minipigs at 3 months. RESULTS: At 3 days, magnesium alloy stents were intact, but started to show signs of degradation by 28 days. There was no evidence of stent particle embolization, thrombosis, excess inflammation, or fibrin deposition. At 28 days and 3 months, neointimal area was significantly less in magnesium alloy stent segments (2.44 +/- 0.88 mm(2) and 1.16 +/- 0.19 mm(2)) as compared with the stainless steel stent segments (5.03 +/- 1.5 mm(2) and 1.72 +/- 0.68 mm(2), P < 0.001 and 0.02). Quantitative coronary analysis indicates that percentage area stenosis and percentage diameter stenosis in magnesium alloy stent segments improved significantly at 3 months as compared to 28 days. Despite decreased neointimal hyperplasia, lumen area of the magnesium alloy stented vessels did not improve significantly. CONCLUSION: Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.