1. Drug Eluting Stents (Des)
Presenter : Dr. Shantibhushan K Kamble, PG Guide: Dr. S. B. Patel

2. 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

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.

4. 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).

5. 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

6. 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.

7. 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

8. Types of Stent

9. Parts of DES
• Parts of DES
– Stent Platform
– Coating
– Drug

10. 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)

11. 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

12. 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).

14. 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

15. 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.

16. Complication from stent
Pathopysiology of stent thrombosis

17. Types Of Drug
Anti-Neoplastics Anti-Proliferative Migration Enhanced Healing
Inhibitors Factors
Sirolimus Taxol (paclitaxel) Batimistat BCP671
Tacrolimus Actinomycin Prolyl Hydrosylase VEGF
Inhibitors
Everolimus Methotraxate Halofunginone Estradiols
Leflunomide Angiopeptin C-preteinase NO Donor
Inhibitors Compounds
M-Prednisolone Vincristine Probucol EPC antibodies
Dexamethasone Mitomycine
Cyclosporine Statins
Mycophenolic Acid C MYC antisense
Mizoribine Abbott ABT-578

18. Cell Cycle Inhibition
Sirolimus S
Everolimus
ABT-578 X
G0 G1 G2
Cell
Resting cycle
Cell
division
X M
Paclitaxel

19. First Generation Stent
• Sirolimus eluting stent
• Paclitaxel eluting stent

20. 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.

21. 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

22. 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

23. 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.

24. 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

25. 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

26. 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.

27. 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

28. Everolimus
It 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.

29. 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

30. How successful is
Angioplasty 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.

31. Comparative Studies
SES PES P value
Major adverse cardiac 6.2 percent 10.8percent 0.009
events
MI 2.8percent 3.5 percent 0.49
Angiographic restenosis 6.6 percent 11.7 percent 0.02
Target-lesion 4.8percent 8.3percent 0.03
revascularization

32. 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.

33. Spirit III Trial
At 12 mths Everolimus- paclitaxel eluting P value
eluting stent stent (taxus)
Major adverse 5.8% 9.9% <0.01
cardiac event
Target vessel 3.3% 5.6% <0.05
revascularization

34. 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.

35. 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 you're overweight or obese.
 Reduce stress.
 Take medicines as your doctor directs to lower high blood pressure or
high blood cholesterol.

36. Future prospective
• Possible upcoming drug in future
– Many research and development activities are under way.
 Dexamethasone
 Estradiol
 Pimecrolimus

38. 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.

39. 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 .

41. DES Producing Companies
Johnson & Johnson / sirolimus (CYPHER)
Medtronic / zotarolimus (ENDEAVOR)
Abbot / Everolimus ( XIENCE )
Boston Scientific ( TAXUS)
Biosensors Int. (BIOMATRIX)

42. Cost of stent
• Sirolimus Stent approximately 80,000-
100,000.
• Supralimus Stent approximately 60,000.
• Bare metal Stent- 20,000 - 40,000.

43. 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

44. 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.

45. Thank you !