Medtronic Coronary Stents ––––– Resolute Integrity™ Stent SystemThe Resolute Integrity™ stent system is used worldwide to treat coronary artery disease (CAD),the narrowing and hardening of the blood vessels that nourish the heart. Developed byMedtronic, this next-generation drug-eluting stent (DES) was approved by the United StatesFood and Drug Administration (FDA) for the treatment of CAD and is the first and only DES tobe approved for use in CAD patients who also have diabetes.i CAD is a leading cause of deathin the US, killing almost half a million Americans each year.ii Research shows that people withdiabetes have a two- to three-fold increasedrisk for CAD and two- to four-fold higherCAD morbidity and mortality rates.iiiThe Resolute Integrity DES is used in aminimally-invasive, catheter-based Resolute Integrity DES is the first and only drug-eluting stentprocedure called percutaneous coronary approved by the FDA for CAD patients who also have diabetes.intervention (PCI), which is analternative to open heart surgery. During PCI, an interventional cardiologist inserts a tinyballoon into the vessel at the site of the narrowing. Crimped tightly on the end of the balloon isthe stent, a tiny mesh cylinder that is coated with a drug designed to prevent the vessel fromrenarrowing. When the balloon is inflated, the stent expands in the narrowed artery and thedrug is released over time into the vessel wall. With the stent expanded, the balloon is deflatedand removed. The stent remains in place, providing a scaffold to keep the artery open andrestoring normal blood flow to the heart.The Resolute Integrity stent system consists of four components: Continuous sinusoid technology forms the flexible stent platform. The MicroTrac™ delivery system takes the stent to the target lesion and deploys it by inflating the balloon. The highly biocompatible BioLinx® polymer regulates drug elution and allows healing. The antiproliferative drug zotarolimus limits excessive tissue growth.
Several features distinguish the Resolute Integrity DES from other devices on the market. Theseinclude its benefit to treat CAD patients who also have diabetes, as well as its deliverability androbust clinical program.Benefit to CAD Patients with DiabetesHistorically it has been difficult to treat CAD patients with diabetes because they tend to havenarrower, more tortuous arteries with more diffuse disease (for example, plaque that is spreadover a longer section within the artery) and persistently elevated blood-sugar levels. All of thesefactors can increase the rate of procedural complications and long-term safety risks. As a result,many such patients have undergone open heart surgery, which is more invasive and requireslonger hospital stays and recovery time compared with stenting procedures.The Resolute Integrity DES is the first device of its kind to be approved by the FDA for treatingCAD patients who also have diabetes. About 30 percent of the patients in the global RESOLUTEclinical program had diabetes––a proportion that mirrors current clinical practice and oneadequate to compare the safety and effectiveness data between CAD patients with and withoutdiabetes. At one-year follow-up in 867 standard-riskiv diabetes patients who participated in thetrials, the Resolute® DES showed low rates of target lesion revascularizationv (3.3%) and stentthrombosisvi (0.3%), similar to the stent’s performance in patients without diabetes.The FDA approval in February 2013 of the 34-mm and 38-mm versions of the Resolute IntegrityDES offer physicians a new, longer stent that is designed to treat patients with diffuse disease,many of whom also have diabetes (nearly 40% of patients with long lesions in the 38-mmanalysis of the RESOLUTE clinical program also had diabetes).xDeliverabilityIn this context, deliverability refers to the device’s ability to traverse the patient’s vascularsystem and reach the narrowed arterial segment. The 38-mm length of the Resolute IntegrityDES has been shown in bench testing to offer superior deliverability compared with the 18-mmXience V® DES and the 20-mm Promus Element™ Plus DES vii––due to an advance in biomedicalengineering called continuous sinusoid technology (CST). Developed by Medtronic engineers,CST enables each stent to form from a single wire, comparable to a flexible spring. This uniquetechnology allows for excellent conformabilityviii ––the ability of the stent to conform to thenatural shape of the vessel––and deliverabilityvii, without compromising other important stentdesign characteristics like radial and longitudinal strength. CST represents Medtronic’splatform of the future for all coronary stents.Robust Clinical ProgramThe RESOLUTE clinical program involves hundreds of medical centers in more than 25countries across the globe. It enrolled more than 5000 patients (nearly 30 percent of whom haddiabetes) in a combination of single-arm and randomized trials. In the clinical trial conductedwith US patients (N = 1402), known as RESOLUTE US, the Resolute DES showed powerfulclinical performance across all safety and efficacy endpoints. At one year, patients (n = 1376)showed low rates of target lesion failure (4.7%), target lesion revascularization (2.8%) and stentthrombosis (0.1%).ix For the approval of the 34-mm and 38-mm version of the Resolute IntegrityDES, data on 222 patients from the RESOLUTE US and RESOLUTE Asia clinical studies whohad long lesions were reviewed by the FDA. At one year, these patients had a low rate of target
lesion failure (5.4%) and among the nearly 40% of these patients who had diabetes, their clinicaloutcomes were similar to patients without diabetes.xIndications, Safety & WarningsIndicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is indicated for improvingcoronary luminal diameters in patients, including those with diabetes mellitus, withsymptomatic ischemic heart disease due to de novo lesions of length ≤35 mm in native coronaryarteries with reference vessel diameters of 2.25 mm to 4.20 mm.ContraindicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is contraindicated for use in:• Patients with a known hypersensitivity or allergies to aspirin, heparin, bivalirudin,clopidogrel, prasugrel, ticagrelor, ticlopidine, drugs such as zotarolimus, tacrolimus, sirolimus,everolimus or similar drugs or any other analogue or derivative• Patients with a known hypersensitivity to the cobalt-based alloy (cobalt, nickel, chromiumand molybdenum) • Patients with a known hypersensitivity to the BioLinx® polymer or itsindividual componentsCoronary artery stenting is contraindicated for use in: • Patients in whom antiplatelet and/oranticoagulation therapy is contraindicated • Patients who are judged to have a lesion thatprevents complete inflation of an angioplasty balloon or proper placement of the stent or stentdelivery systemWarnings• Please ensure that the inner package has not been opened or damaged as this would indicatethe sterile barrier has been breached. • The use of this product carries the same risks associatedwith coronary artery stent implantation procedures, which include subacute and late vesselthrombosis, vascular complications and/or bleeding events. • This product should not be usedin patients who are not likely to comply with the recommended antiplatelet therapy.Precautions• Only physicians who have received adequate training should perform implantation of thestent. • Stent placement should only be performed at hospitals where emergency coronaryartery bypass graft surgery can be readily performed. • Subsequent stent restenosis or occlusionmay require repeat catheter-based treatments (including balloon dilatation) of the arterialsegment containing the stent. The long-term outcome following repeat catheter-basedtreatments of previously implanted stents is not well characterized. • The risks and benefits ofthe stent implantation should be assessed for patients with a history of severe reaction tocontrast agents. • Do not expose or wipe the product with organic solvents such as alcohol. •When drug-eluting stents (DES) are used outside the specified Indications for Use, patientoutcomes may differ from the results observed in the RESOLUTE pivotal clinical trials.• Compared to use within the specified Indications for Use, the use of DES in patients and lesionsoutside of the labeled indications, including more tortuous anatomy, may have an increasedrisk of adverse events, including stent thrombosis, stent embolization, myocardial infarction
(MI) or death. • Care should be taken to control the position of the guide catheter tip duringstent delivery, deployment and balloon withdrawal. Before withdrawing the stent deliverysystem, visually confirm complete balloon deflation by fluoroscopy to avoid guiding cathetermovement into the vessel and subsequent arterial damage. • Stent thrombosis is a low-frequency event that is frequently associated with MI or death. Data from the RESOLUTEclinical trials have been prospectively evaluated and adjudicated using the definition developedby the Academic Research Consortium (ARC).The safety and effectiveness of the Resolute Integrity stent have not yet been established in thefollowing patient populations: • Patients with target lesions which were treated with priorbrachytherapy or the use of brachytherapy to treat in-stent restenosis of a Resolute Integritystent • Women who are pregnant or lactating • Men intending to father children• Pediatric patients • Patients with coronary artery reference vessel diameters of <2.25 mm or>4.20 mm • Patients with coronary artery lesions longer than 35 mm or requiring more than oneResolute Integrity stent • Patients with evidence of an acute MI within 72 hours of intendedstent implantation • Patients with vessel thrombus at the lesion site • Patients with lesionslocated in a saphenous vein graft, in the left main coronary artery, ostial lesions or bifurcationlesions • Patients with diffuse disease or poor flow distal to identified lesions • Patients withtortuous vessels in the region of the target vessel or proximal to the lesion • Patients with in-stent restenosis • Patients with moderate or severe lesion calcification at the target lesion •Patients with occluded target lesions including chronic total occlusions • Patients with three-vessel disease • Patients with a left ventricular ejection fraction of <30% • Patients with a serumcreatinine of >2.5mg/dl • Patients with longer than 24 months of follow-upThe safety and effectiveness of the Resolute Integrity stent have not been established in thecerebral, carotid or peripheral vasculature.Potential Adverse EventsOther risks associated with using this device are those associated with percutaneous coronarydiagnostic (including angiography and IVUS) and treatment procedures. These risks (inalphabetical order) may include but are not limited to: • Abrupt vessel closure • Access sitepain, hematoma or hemorrhage • Allergic reaction (to contrast, antiplatelet therapy, stentmaterial, or drug and polymer coating) • Aneurysm, pseudoaneurysm or arteriovenous fistula(AVF) • Arrhythmias, including ventricular fibrillation • Balloon rupture • Bleeding • Cardiactamponade • Coronary artery occlusion, perforation, rupture or dissection • Coronary arteryspasm • Death • Embolism (air, tissue, device or thrombus) • Emergency surgery: peripheralvascular or coronary bypass • Failure to deliver the stent • Hemorrhage requiring transfusion• Hypotension/hypertension • Incomplete stent apposition • Infection or fever • MI •Pericarditis • Peripheral ischemia/peripheral nerve injury • Renal failure • Restenosis of thestented artery • Shock/pulmonary edema • Stable or unstable angina • Stent deformation,collapse or fracture • Stent migration (or embolization) • Stent misplacement• Stroke/transient ischemic attack • Thrombosis (acute, subacute or late)Adverse Events Related to ZotarolimusPatients’ exposure to zotarolimus is directly related to the total amount of stent lengthimplanted. The actual side effects/complications that may be associated with the use of