Drug Eluting Stents (Des) Presenter : Dr. Shantibhushan K Kamble, PG Guide: Dr. S. B. Patel
Introduction• Cardiovascular diseases cause more than 15 million deaths in the world each year. (WHO; Geneva).• They account for 50% of all deaths in several developed countries.• Healthcare costs (estimated at $50–150 billion per year)• Newer techniques like per cutaneous interventions(PCI) by using stent increases survival rate and decreases morbidity.• Advantage: Requires only a short (1-day) hospitalization, greatly decrease recovery time and expense compared to coronary bypass surgery.• lower elective mortality rate than bypass surgery (0.4–1.0%, compared to a rate of 1–3
Historical account ….• 3000 B.C. — Egyptians perform bladder catheterizations using metal pipes.• 400 B.C. — Catheters prepared from hollow reeds and pipes are used in cadavers.• 1711 — Hales conducts the first cardiac catheterization of a horse using brass pipes, a glass tube and the trachea of a goose.• 1844 — French physiologist Bernard coins the term "cardiac catheterization" .• 2004 — Boston Scientific gets its Taxus drug- eluting stent approved.
Metallic stents• First introduced in the U.S. in 1994• These devices differ from each other with respect to : i) Composition (e.g., stainless steel, cobalt chromium alloy, or nickel chromium alloy), ii) Architectural design, and iii) Delivery system (i.e, the balloon catheter that delivers the stent).
Metallic stents Bare-metal stents provide structural support the artery after angioplasty. Bare-metal stents help to prevent the artery from re-narrowing. However, about 25% of the time, the arteries may become blocked up again after placement of a bare-metal stent
Drug releasing stents Drug releasing stents are coated with an anti-proliferative drug, which allows drug elution into the coronary wall for weeks after stent implantation. Studies have shown that they are better than bare metal stents as they reduce the incidence of re-stenosis and overall cardiac adverse events.
Drug releasing stents A drug-coated stent is a bare-metal stent with a special drug coating. It also support the artery to kept open after angioplasty. In addition, the stent releases a drug over time to further reduce the chance of re-blockage. Arteries commonly become blocked up again about 7% of the time with drug-coated stents compared to about 25% for bare-metal stents
Types of Stent
Parts of DES• Parts of DES – Stent Platform – Coating – Drug
Indications of using Stents Drug-eluting stents (DES) are generally superior to bare-metal stents as regards Major Adverse Cardiac Events (MACE, generally defined as death, myocardial infarction, or the need for a repeat revascularization procedure.) Stents are indicated to improve the diameter of the coronary artery lumen, when narrowing causes ischemia (to the muscle supplied by that artery)
What Are the Risks of Coronary Stenting• The risk of complications is higher in: People aged 75 and older People who have kidney disease or diabetes Women People who have poor pumping function in their hearts People who have extensive heart disease and blockages
Risks Bleeding from the blood vessel where the catheter was placed. Damage to blood vessels from the catheter. An allergic reaction to the dye given during the angioplasty. An arrhythmia (irregular heartbeat). Damage to the kidneys caused by the dye used. Heart attack (3–5 percent of people). Stroke (less than 1 percent of people).
Complications From Stents• Restenosis – There is a chance that the artery will become narrowed or blocked again in time, often within 6 months of angioplasty
Complications From Stents• Blood Clots Taking medicine as prescribed by your doctor can lower the risk of blood clots. People with medicine Coated stents are usually advised to take an anti clotting drug, such as clopidogrel and aspirin, for months to years to lower the risk of blood clots.
Complication from stent Pathopysiology of stent thrombosis
Cell Cycle Inhibition Sirolimus S Everolimus ABT-578 X G0 G1 G2 CellResting cycle Cell division X M Paclitaxel
First Generation Stent• Sirolimus eluting stent• Paclitaxel eluting stent
Sirolimus The first Approved DES in Europe (2002). After a larger pivotal trial, the device received FDA approval and was released in the U.S. in 2003. It is an immunosuppresant drug , that inhibits the cytokine stimulated proliferation of T cells. MOA: Binds to FK-binding protein-12(FKBP-12) FKBP-12 binds to specific cell cycle regulatory protein , the mammalian target of rapamycin (mTOR) kinase mTOR inhibition prevents cell cycle progression from G1 to S.
sirolimus• Sirolimus is released from the CYPHER stent• It is dependent upon concentration of drug both inside and outside the polymer matrix.• Approximately 50 percent of the total drug is eliminated within the first 10 days of implantation.• The drug is 90 percent removed from the stent by about 60 days• Completely removed by about 90 days• Peak drug concentration occurs about 4 hours
sirolimus• Indications : In pt with symptomatic ischemic disease due lesion of length < 30 mm in native coronary arteries with reference diameter of >2.5 to < 3.5 mm• Contraindications: Hypersensitivity to sirolimus Hypersensitivity to polymer• ADRs’: Arrhythmias Myocardial infarction Pesudoanuerysm Vessel spasm
Paclitaxel• Paclitaxel-eluting stents led to FDA approval of the Taxus stent in 2004.• Paciltaxel is in the antineoplastic family of compounds• Mechanism of Action: Paciltaxel binds to microtubules in dividing cells and causes them to assemble, thereby preventing mitosis.• Indications: For improving luminar diameter for the treatment of de novo lesion in native coronary arteries > 2.5 to < 4mm in diameter in lesion < 28 mm in length.
Paclitaxel• Contraindications: Allergy Not on antiplatelets & anticoagulants Infection at the site of access Irregular heart beat Total occlusion of vessels• ADR’s: Abnormal liver values Anemia GI disturbances Loss of hair Muscle pain
Why need 2nd generation DES• Further reduce in restenosis.• To prevent inhibition of endothelial cells.• Reduction of risk of stent thrombosis.• Second generation stent Zotarolimus eluting stent Everolimus eluting stent
Zotarolimus Zotarolimus is an immunosuppressant MOA : • Binds to FKBP 12,leading to the formation of a trimetric complex with the protein kinase mTOR• Inhibition of mTOR activity• Inhibition of cell cycle progression from the GI to the S phase. Indications: In atherosclerosis to the degree that it has caused their coronary arteries to narrow.
Zotarolimus Contraindications:• Allergic to Zotarolimus or the metal or polymer coating that is in the stent.• Cannot take blood thinners or aspirin• Those who have an arterial blockage that is so severe that the catheter balloon cannot be inflated for placing the stent. ADRs’• Although actual side effects are not completely known• S/E on IV rash, abdominal pain, infection, headache, dry skin, hematuria, diarrhea, anemia and application site reaction
EverolimusIt is a novel semisynthetic Macrolide immunosuppresant Synthesized by chemical modification of rapamycin (sirolimus )MOA: Inhibition of mTOR appears to be the mechanism by which everolimus inhibits cell proliferation.Indications: Pt with symptomatic heart disease due to denovo coronary artery lesions ( length ≤ 28mm) with reference vessel diameter of 2.25 mm to 4.25mm.
Everolimus• Contraindications : Pt who can not receive antiplatelates Pt with lesion that prevent complete angioplasty balloon inflation or proper placement of stent. With hypersensitivity to everolimus related compounds• ADR’s: Abrupt closure Allergy & Hypersensitivity to contrast agent or cobalt. Bleeding complications MI
How successful isAngioplasty and stenting?• Angioplasty/ stenting is successful in treating the narrowing/blockage of the artery in the vast majority of patients (over 70%).• In the small number of patients in whom the procedure is unsuccessful, a surgical bypass operation may be offered as an alternative.
Comparative Studies SES PES P valueMajor adverse cardiac 6.2 percent 10.8percent 0.009eventsMI 2.8percent 3.5 percent 0.49Angiographic restenosis 6.6 percent 11.7 percent 0.02Target-lesion 4.8percent 8.3percent 0.03revascularization
Endeavor III Study• At 9 months follow up target rate revascularization rate was 9.8 % in zotarolimus eluting stent compared to 3.5% (p-0.04) in sirolimus eluting stent .• However at 24 months both showed same results.
Spirit III TrialAt 12 mths Everolimus- paclitaxel eluting P value eluting stent stent (taxus)Major adverse 5.8% 9.9% <0.01cardiac eventTarget vessel 3.3% 5.6% <0.05revascularization
Life after stenting• Going Home Most people go home 1 to 2 days after the procedure. Instructions from your doctor• Medications Medicine to prevent blood clots from forming. e.g..Aspirin and Clopidogrel Taking medicine as directed is very important. If a stent was inserted, the medicine reduces the risk that blood clots will form in the stent. Blood clots in the stent can block blood flow and cause a heart attack.
Life after stenting• Recovery & Recuperation Most people recover from angioplasty and return to work about one week after being sent home• Lifestyle Changes Making healthy lifestyle changes can help treat CAD and maintain the good results from angioplasty Quit smoking if you smoke. Be physically active. Lose weight if youre overweight or obese. Reduce stress. Take medicines as your doctor directs to lower high blood pressure or high blood cholesterol.
Future prospective• Possible upcoming drug in future – Many research and development activities are under way. Dexamethasone Estradiol Pimecrolimus
Cobalt chrome alloy VS stainless steel• More Strong.• More radio-opaque• Struts can be thinner which seems to reduce the degree of restenosis.• less nickel than 316L stainless steel and so may cause less allergy.
Bioabsorbable stents• Since stent itself is foreign body, so prothrombogenic.• Igaki-Tamai stent- from poly L lactic polymer• 25 pts have implanted it , with target lesion revascularization rate of 6.7% at 6 moths.• BVS STENT - Release everolimus from poly L lactic polymer .
Cost of stent• Sirolimus Stent approximately 80,000- 100,000.• Supralimus Stent approximately 60,000.• Bare metal Stent- 20,000 - 40,000.
In Our Hospital• In our hospital and in most of the hospitals we use only drug eluting stents• Sirolimus is used always• Occasionally Supralimus• Rarely Bare metal stents are used
summ• Cardiovascular diseases are main cause of premature mortality and morbidity in the world• Many treatments are available for T/t of cardiac disease like medications , PCI, change in the dietary habits• The drug eluting stents are promising one ,which prevents or decrease this mortality and morbidity due CVDs.• Many trial shows that Sirolimus eluting stents are best and commonly used world wide.• In case of Failure of DES alternatives are available in forms of coronary artery bypass grafting.