sirolimus and Peripheral-Vascular-Diseases

Noncoronary atherosclerotic vascular disease, including symptomatic lower extremity peripheral arterial disease (PAD), promises to extract a steadily rising medical and economic toll over the coming decades. Although drug-eluting stents have led to substantial advances in the management of coronary atherosclerosis, endovascular treatment of noncoronary, peripheral arterial lesions continues to yield high restenosis rates and early clinical failures. In this report, we review recent developments in microfabrication and nanotechnology strategies that offer new opportunities for improving stent-based technology for the treatment of more extensive and complex lesions. In this regard, stents with microfabricated reservoirs for controlled temporal and spatial drug release have already been successfully applied to coronary lesions. Microfabricated needles to pierce lesions and deliver therapeutics deep within the vascular wall represent an additional microscale approach. At the nanoscale, investigators have primarily sought to alter the strut surface texture or coat the stent to enhance inductive or conductive schemes for endothelialization and host artery integration. Nanotechnology research that identifies promising strategies to limit restenosis through targeted drug delivery after angioplasty and stenting is also reviewed.

Topics: Angioplasty; Graft Occlusion, Vascular; Humans; Nanotechnology; Paclitaxel; Peripheral Vascular Diseases; Prosthesis Design; Sirolimus; Stents; Thrombosis

Transcatheter endovascular therapy for peripheral atherosclerotic disease has become more popular. In general, good results have been reported in focal aortoiliac disease. However, the long-term patency of angioplasty in longer, more distal lesions has been less satisfactory. Stenting has not been shown to improve long-term patency compared to angioplasty alone. Drug-eluting stents have shown promise in preventing coronary restenosis, and preliminary results in peripheral arterial disease are encouraging. This review article will discuss the current status of endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease, the theoretic and experimental basis for the use of drug-eluting stents, and the preliminary results in human studies.

Topics: Angiogenesis Inhibitors; Anti-Inflammatory Agents; Arterial Occlusive Diseases; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; Peripheral Vascular Diseases; Prosthesis Design; Recurrence; Sirolimus; Stents; Vascular Patency

To evaluate the long-term follow-up of the unrestricted use of a biodegradable polymer-coated drug-eluting stent in patients undergoing percutaneous coronary intervention (PCI).. The Nobori 2 study was a prospective, multicentre, observational registry evaluating the safety and the efficacy of the biodegradable polymer biolimus-eluting stent (BP-BES) among 3067 patients recruited at 125 international sites. The primary combined endpoint was a composite of cardiac death, myocardial infarction and target-lesion revascularisation (TLR).. Five-year follow-up was available in 2738 (89.3%) patients. The combined endpoint occurred in 268 patients (10%, 95% CIs 8.9% to 11.3%) at 5 years, with 3.9% of events during the first year and 6.2% during years 1-5 of follow-up. Cumulative rates of TLR and definite/probable stent thrombosis were 5.3% (95% CI 4.5% to 6.3%) and 1.1% (95% CI 0.8% to 1.6%), respectively. Between 1 and 5 years, TLR and very late stent thrombosis rates were 3.5% (95% CI 2.8% to 4.4%) and 0.6% (95% CI 0.3% to 1.1%), respectively. Previous PCI (HR, 2.05, 95% CI 1.68 to 2.50), moderate-to-severe renal disease (HR, 1.89, 95% CI 1.30 to 2.74) and peripheral vascular disease (HR, 1.86, 95% CI 1.38 to 2.52) were the three most powerful independent predictors of the combined endpoint at 5 years.. The final 5-year follow-up of the Nobori 2 registry demonstrates the safety and effectiveness of the BP-BES in an unselected, broadly inclusive cohort of PCI patients, highlighting the excellent performance of this coronary stent technology after polymer biodegradation.. ISRCTN81649913; Results.

Topics: Absorbable Implants; Aged; Coronary Thrombosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Kidney Diseases; Male; Middle Aged; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Polymers; Prospective Studies; Prosthesis Design; Registries; Retreatment; Sirolimus; Treatment Outcome

Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0 × 20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50 ± 25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.

Topics: Absorbable Implants; Animals; Drug Implants; Drug-Eluting Stents; Equipment Failure Analysis; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Peripheral Vascular Diseases; Polyesters; Prosthesis Design; Sirolimus

No data are currently available on the role of oral sirolimus in the prevention of recurrent stenosis in the periphery. We report the effects of oral sirolimus in the prevention of recurrent infrainguinal obstructions in patients with complex peripheral arterial disease. Three patients with ischemic rest pain of the lower limbs and repeated short-term need for surgical and/or endovascular revascularization: 9 times within 12 months, 7 times within 15 months, 11 times within 26 months, respectively. Oral sirolimus on a case by case basis, resulted in less frequent restenosis and longer intervention-free intervals: three re-interventions within 37 months in the first patient, one balloon angioplasty within 17 months in the second, and three re-interventions within 21 months in the third patient, respectively. Side effects, in particular dyspepsia and diarrhoea, were mild and tolerable. To our knowledge, this is the first report to show that oral sirolimus was successfully administered in patients with recurrent excessive neointimal proliferation after revascularization of peripheral arterial lesions lowering the necessity of re-intervention and hence prolonging intervention-free intervals.

Topics: Administration, Oral; Aged; Angioplasty, Balloon; Cardiovascular Agents; Constriction, Pathologic; Female; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Vascular Diseases; Reoperation; Saphenous Vein; Secondary Prevention; Sirolimus; Thrombectomy; Treatment Failure; Vascular Surgical Procedures

Thrombotic microangiopathy (TMA) is a well-recognized complication after transplantation. The purpose of this study was to describe our center's experience with this complication after lung transplantation.. We retrospectively reviewed cases of TMA among patients who underwent lung transplantation between January 1, 1999 and December 31, 2003 (n = 257). The cases were characterized and the outcomes were analyzed. Univariate and multivariate Cox regression models were constructed to identify potential risk factors for TMA.. Twenty-four cases of TMA developed in 20 recipients. Thirteen cases occurred in the setting of another illness and 11 cases were isolated complications. Multivariate Cox regression models identified female gender, history of TMA, and the immunosuppressive regimen as independent predictors of TMA. Maintenance immunosuppression with the combination of a calcineurin inhibitor and sirolimus carried a significantly higher risk of TMA than a calcineurin inhibitor alone. After the diagnosis of TMA, calcineurin inhibitors were stopped in 18 cases; however, in 6 cases in which the onset of TMA coincided with the addition of sirolimus to a calcineurin inhibitor, only sirolimus was discontinued. Plasmapheresis was performed for severe cases (n = 10). TMA remitted in all cases, and an alternate calcineurin inhibitor was introduced in 14 cases. TMA recurred in 4 recipients, a median 253 days after the initial episode. The median survival after the onset of TMA was 377 days.. TMA is a serious complication after lung transplantation, and the risk is highest when sirolimus is used in combination with a calcineurin inhibitor.

Topics: Female; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Peripheral Vascular Diseases; Proportional Hazards Models; Retrospective Studies; Sirolimus; Survival Rate; Thrombosis

To assess the safety and efficacy of sirolimus-eluting stents (SESs) in the treatment of severe intermittent claudication and critical limb ischaemia with "below-the-knee" lesions, unsuitable for surgery.. Limited published evidence suggests that drug-eluting stents may offer significant improvements in the treatment of infrapopliteal lesions.. Thirty consecutive patients with either severe intermittent claudication or critical limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES. Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of patients were male and 36% diabetic. The primary endpoint was clinical improvement and healing of ulcers at short term (1 month) and mid term (7.7 months). The secondary endpoint was primary vessel patency rate (angiographic or duplex assessment). All patients received clopidogrel (75 mg daily) or ticlopidine (150 mg daily) for 2 months or longer.. Angiographic and procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb salvage was obtained in 100% of patients. Other events were: two cardiac deaths unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome, one contralateral CLI, and three recurrent homolateral claudication cases. All surviving patients had a mid-term clinical improvement with 97% of primary patency (56 patent arteries on 58 arteries).. Treatment of "below-the-knee" lesions with SES may provide an alternative treatment for patients with CLI.

Topics: Adult; Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Safety; Female; Follow-Up Studies; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Popliteal Artery; Prospective Studies; Research Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Topics: Coronary Stenosis; Humans; Immunosuppressive Agents; Leg; Peripheral Vascular Diseases; Sirolimus; Stents

The main cause of illness and death after the first year of heart transplantation is vasculopathy of the cardiac allograft, probably initiated by early immunological and non-immunological endothelial damage. The incidence of multiple episodes of grade 3A rejection 6 months after primary heart transplantation was lower with everolimus (1.5 mg, 8.1% and 3 mg, 6.6%) than in the azathioprine group (14%). Allograft vasculopathy was less frequent with everolimus than azathioprine. A follow-up study is necessary to determine whether these effects translate into the important end points of reduced incidences of death, graft loss or a second transplantation.

Topics: Adrenal Cortex Hormones; Aged; Azathioprine; Cholesterol; Cholesterol, LDL; Clinical Trials as Topic; Creatinine; Cyclosporins; Drug Therapy, Combination; Everolimus; Graft Rejection; Heart Transplantation; Humans; Middle Aged; Multicenter Studies as Topic; Peripheral Vascular Diseases; Sirolimus; Transplantation, Homologous