1. Peri-Operative Management of Drug Eluting Stents
Stephen T. Thew, MD, FACC
Heart Clinics Northwest

2. Bleeding Stent Thrombosis
Balance
Bleeding Stent Thrombosis

3. Outline/Highlights Timing of elective surgery
What to do with medications
Stopping anti-platelet meds
When to restart
Post operative concerns

4. Timing of Surgery Post-Stenting
Bare Metal Stents
Wait days for elective surgery
But do it prior to 6 months (or wait > 1 yr)
Drug Eluting Stents
Wait at least 6 months for elective surgery
Ideal - 1 year for elective surgery (??)

5. Anti-platelet medications
If possible continue all anti-platelet medications
If Plavix (P2Y12) must be stopped do so 5-7 days before surgery and re-start ASAP with mg bolus
REALLY try to continue aspirin, if stopped do so 5 days before and restart ASAP

6. Anti-platelet medications
Consider “bridging therapy” with IV administration of IIb/IIIa inhibitor (short half-life) in certain situations
If bridging, start IV IIb/IIIa 2-3 days prior to surgery

7. Post operative concerns
Close monitoring for bleeding
Chest pain, hypotension, tachycardia all need very prompt attention
Elective surgery should be done at hospital with 24 hour availability of PCI capable cath lab

8. Peri-op DES: Scope of the Problem
In the US over 600,000 percutaneous coronary interventions (PCI) are done every year
The majority of PCIs involve drug eluting stent placement

9. Peri-op DES: Scope of the Problem
Dual Anti-Platelet Therapy (DAPT) includes aspirin in addition to a P2Y12 inhibitor (Plavix, Prasugrel, Brilinta, Ticlid)
Following Drug-Eluting Stent (DES) placement, DAPT is recommended for 12 months by ACC/AHA guidelines

10. Peri-op DES: Scope of the Problem
About 5% of patients undergoing PCI will need non-cardiac surgery within 1 year
About 30,000 procedures annually
Roughly 1% of elective non-cardiac surgery pts. had PCI in the preceding year

11. Peri-op DES What Problems are There?
Increased risk of myocardial infarction
Risk of stent thrombosis
Increased risk of bleeding due to DAPT
Migration of the stent ?
Interference with diagnostic/imaging studies?

12. Why do Cardiologists have a love affair with DES?
Because they work so well
Work well for what?
Compared to what?
Are there alternatives besides DES?

13. Brief history of Coronary Revascularization Surgical Bypass (CABG)
Prior to the 1960s angina was treated with Nitroglycerin
Vineberg procedure had been occasionally used (LIMA grafted directly to the anterior wall myocardium)
1967 the first CABG was performed at the Cleveland Clinic – an SVG placed to LAD

14. Brief history of Coronary Revascularization Limitations of CABG
Surgery required
Prolonged recovery times, in hospital and at home
Repeat procedures can be done, but limited by available conduit, increased morbidity and again prolonged convalescence

15. Brief history of Coronary Revascularization Balloon Angioplasty (PTCA)
In 1977 Andreas Gruentzig preformed the first balloon angioplasty in Zurich, Switzerland
Recovery time was minimal, cost was lower, repeat procedures were more practical than re-do CABG

16. Brief history of Coronary Revascularization Limitations to PTCA
Complications
Acute vessel closure
Dissection
Intra-coronary thrombus
Emergent CABG
Durability
Restenosis
Elastic Recoil
Intimal Hyperplasia

17. Brief history of Coronary Revascularization Coronary Stenting
In 1994 the FDA approves the use of coronary stents
By the late 1990’s about 85% of coronary interventions utilized stents
Restenosis reduced from 30-40% to 20-30%
Many of the limitations of PTCA were treated/prevented with stents

18. Durability (Restenosis)
Brief history of Coronary Revascularization PTCA limitations now treated by stents
Complications
Acute vessel closure
Dissection
Durability (Restenosis)
Elastic Recoil – essential resolved
Intimal Hyperplasia – actually worsened
Net effect was still significant reduction in restenosis

19. Brief history of Coronary Revascularization Limitations of Stents
Stent Thrombosis
Ticlid in addition to aspirin markedly reduced SAT
Formed the concept of DAPT
Plavix (clopidogrel) replaced Ticlid in late 1990’s
Durability – (Restenosis)
Elastic recoil resolved, but neointimal hyperplasia got worse
Restenosis rates were 20-30%
Small Vessels, Diabetics, diffuse disease all had even higher restenosis rates

20. Brief history of Coronary Revascularization Drug Eluting Stents
2003 the first DES is approved by FDA
DES deliver locally, a high dose of a chemotheraputic agent to inhibit neo- intimal growth
Restenosis rates dropped to around 4-5%

21. Why Cardiologists Love DES
PCI reduces mortality and morbidity in acute coronary syndromes
PCI is effective in controlling anginal symptoms
Patient recovery time is short
Essentially unlimited future procedures can be preformed if needed
Long term durability is very good

22. Limitations of Drug eluting stents
Increased, but later, stent thrombosis in DES
Late (>30 days)
Very Late (>1 year)
Inhibition of neo-intimal growth also inhibits endothelial formation inside the stent
Long term (12 month) Plavix was recommended

23. In-stent Restenosis/Endothelialization
Bare-metal stents have essentially complete endothelialization at 4 – 6 weeks
DES at 180 days may still have some incomplete endothelialization

24. Stent Thrombosis Stent thrombosis
Acute –first 24 hours
Sub-acute – first month
Late – first year
Very late - > 1 year
Overall stent thrombosis rate is 1-2 % in first year
Continues to be a major concern

25. Stent Thrombosis
During surgery there is a hypercoaguable state induced
Increased inflammation and platelet activation
A greater degree of hypercoaguability is seen from surgery than during an MI

26. Stent Thrombosis Post surgery rise in thrombogenic risk
- increased catecholamine release
- increased platelet aggregation
- decreased fibrinolysis

27. Stent Thrombosis
Discontinuation of aspirin leads to a ‘rebound’ effect

28. Anti-Platelet Agents in Addition to Aspirin
Oral
Ticlid
Plavix
Effient
Brilinta IV
ReoPro
Integrlin
Aggrastat

29. Oral Anti-Platelet Agents P2Y12 Inhibitors or ADP Receptor Inhibitors
Thienopyridines
Ticlid (ticlopidine)
Plavix (clopidogrel)
Effient (prasugrel)
Non-thienopyridines
Brilinta (ticagrelor)
Peak inhibition in just 2 to 4 hours

30. Anti-Platelet Agents IV - P2Y12 Inhibitors
Currently – none available
Cangrelor is being studied with PCI
IV administration, 3 to 5 minute half life
Was studied in BRIDGE for pre-op use

31. IV Anti-Platelet Medications Glycoprotein IIb/IIIa Inhibitors
ReoPro (abciximab)
Monoclonal anti-body, irreversible binds platelet
Reverse with platelet infusion
Aggrastat (tirofiban)
Integrlin (eptifibatide)
Synthetic peptides, competitive binding to platelet
Platelet transfusions don’t help – (out competed)
Short ½ life – gone in 2 to 4 hours

32. Dual Anti-Platelet Therapy (DAPT)
Aspirin and a P2Y12 inhibitor
Duration:
4 weeks following bare metal stent
12 months following DES
12 months following MI
Continuation of aspirin indefinitely

33. Bleeding Risk During Surgery
Burger, et al – 49,000+ patients, increased bleeding by 1.5, but mostly ‘nuisance’ bleeding
Intracranial procedures did have increased fatal bleeding
TURP may have increased severity level of bleeding

34. Bleeding Risk with Surgery
There is a decrease in CVAs during CEA with pts on aspirin
Better patency of grafts in CABG and vascular by-pass in patients on aspirin
Increased need for blood products, but no increased mortality in CABG patients on Plavix and aspirin

35. Bleeding Risk with Surgery
Burger, et al – 49,000+ patients
Stopping aspirin had higher cardiac, cerebral and peripheral vascular events

36. Surgical Risk and Timing
Non cardiac surgery done less than 6 weeks after PCI has the highest mortality
The single biggest predictor of stent thrombosis is discontinuation of anti-platelet therapy

37. Surgical Risk and Timing
Retrospective study – Ontario, Canada
ONLY elective surgeries
Increased MACE when <45 days
Bare-metal – optimal time 46 – 180 days
DES – optimal time >180 days
> 1 year and risk has plateaued, is no higher than 2-10 years post PCI
Wijeysundera, et al

38. Surgical Risk and Timing
At > 1 year since PCI the risk approximates that of a intermediate non- revascularized patient with 1 or 2 clinical risk factors
Wijeysundera, et al

39. Peri-op Management of DES
Currently no definitive standard of care, mostly expert opinion
Without good prospective data, management is carried out on individual case basis
Length of stent, location, bifurcation, multi-vessel

40. Strategies for Peri-op Management of DES ELECTIVE SURGERY
Elective surgery should be delayed at least until 6 months post DES
Ideally postponed 1 year post DES
P2Y12 - if stopped - 5 to 7 days pre-op, continue aspirin if at all possible
Resume P2Y12 ASAP with 300 or 600mg loading dose

41. Strategies for Peri-op Management of DES
“Bridging Therapy” with GP IIb/IIIa inhibitor
Has NOT been rigorously studied
Integrlin or Aggrastat, NOT ReoPro
Stop Plavix 5-7 days pre-op
Admit 2-3 days pre-op and start IIb/IIIa
Continue aspirin throughout if possible
Restart Plavix as soon as possible post-op

42. Strategies for Peri-op Management of DES URGENT SURGERY
Urgent-Emergent surgeries have 4-fold higher mortality

43. Strategies for Peri-op Management of DES URGENT SURGERY
Continue DAPT if possible - stent thrombosis risk is high
Closed/confined space – intracranial, spinal medullary, posterior chamber ophthalmic surgeries will need DAPT discontinued
If P2Y12 inhibitor stopped, try to maintain aspirin
Restart the P2Y12 inhibitor post surgery (within 24 hours if possible, with 300mg bolus).

44. Strategies for Peri-op Management of DES Post Op issues
Resumption of DAPT as soon as possible
Using bolus dose of P2Y12 inhibitor
Intensive post–op monitoring if off DAPT
Prompt evaluation and intervention for stent thrombosis or any bleeding

45. Strategies for Peri-op Management of DES Post-op Stent Thrombosis
Usually presents as ST elevation MI
Fibrinolytic therapy is contraindicated
Primary PCI is the treatment of choice
When DAPT is interrupted prematurely for surgery it should be done at hospitals with 24 hour cath/PCI availability

46. Strategies for Peri-op Management of DES Post-op Bleeding
Platelet transfusion is only somewhat effective with P2Y12 agents
It’s not effective with Integrlin or Aggrastat, but with short ½ life normal platelet function is restored in about 6 hours
RBC transfusion as needed

47. Summary/Highlights Timing of elective surgery
What to do with medications
Stopping anti-platelet meds (DAPT)
When to restart
Post operative concerns

48. Timing of Surgery Post-Stenting
Bare Metal Stents
Wait days for elective surgery
But do it prior to 6 months (or wait > 1 yr)
Drug Eluting Stents
Wait at least 6 months for elective surgery
Ideal - 1 year for elective surgery (??)

49. Anti-platelet medications
If possible continue all anti-platelet medications
If Plavix (P2Y12) must be stopped do so 5-7 days before surgery and re-start ASAP with mg bolus
REALLY try to continue aspirin, if stopped do so 5 days before and restart ASAP

50. Anti-platelet medications
Consider “bridging therapy” with IV administration of IIb/IIIa inhibitor (short half-life) in certain situations

51. Post operative concerns
Close monitoring for bleeding
Chest pain, hypotension, tachycardia all need very prompt attention
Elective surgery should be done at hospital with 24 hour PCI capable cath lab availability

52. Proposed Approach to the Management of Patients with Previous PCI Who Require Noncardiac Surgery
Balloon
Bare-metal
Drug-eluting
angioplasty
stent
stent
<365 days
> days
< days
>365 days
Time since PCI
<14 days
>14 days
Delay for elective or
Proceed to the
Delay for elective or
Proceed to the
nonurgent
surgery
operation room
nonurgent
surgery
operating room
with aspirin
with aspirin
PCI, percutaneous coronary intervention

53. Proposed Treatment for Patients Requiring PCI Who Need Subsequent Surgery
Acute MI, H risk ACS, or
H risk cardiac anatomy
Stent & continue dual antiplatelet therapy
Bleeding risk of surgery
low
Not low
Timing of surgery
14-29 days
days
>365 days
Bare-metal
stent
Balloon
angioplasty
Drug-eluting
stent

54. Thank you

55. Preoperative Coronary Revascularization With CABG or Percutaneous Coronary Intervention
Coronary revascularization before noncardiac
surgery is useful in patients with stable angina
who have:
● significant left main coronary artery stenosis
● 3-vessel disease (survival benefit is greater when LVEF <0.50)
● 2-vessel disease with significant proximal
LAD stenosis & either EF<0.50 or demonstrable ischemia on noninvasive testing.
Coronary revascularization before noncardiac surgery is recommended for patients with:
● high-risk UA/NSTEMI
● acute STEMI I
IIa
IIb
III A

56. Preoperative Coronary Revascularization With CABG or Percutaneous Coronary Intervention
In patients in whom coronary revascularization with PCI
is appropriate for mitigation of cardiac symptoms & who
need elective noncardiac surgery in the subsequent 12
months, a strategy of balloon angioplasty or bare-metal
stent placement followed by 4-6 weeks of dual-antiplatelet
therapy is probably indicated.
In patients who have received DES & who must undergo urgent surgical procedures that mandate the discontinuation of thienopyridine therapy, it is reasonable to continue ASA if at all possible & restart the thienopyridine as soon as possible. I
IIa
IIb
III B I
IIa
IIb
III C

57. Preoperative Coronary Revascularization With CABG or Percutaneous Coronary Intervention
The usefulness of preoperative coronary revascularization is not well established in:
High risk ischemic patients (e.g. abnormal dobutamine stress echo with at least
5 segments of wall-motion abnormalities)
Low risk ischemic patients with an abnormal dobutamine stress echo
(segments 1-4) I
IIa
IIb
III C I
IIa
IIb
III B

58. Preoperative Coronary Revascularization With CABG or Percutaneous Coronary Intervention
It is not recommended that routine prophylactic coronary
revascularization be performed in patients with stable CAD before noncardiac surgery
Elective noncardiac surgery is not recommended within:
● 4-6 weeks of bare metal coronary stent implantation or within 12 months of drug-eluding coronary stent implantation in patients in whom thienopyridine therapy, or ASA & thienopyridine therapy, will need to be discontinued perioperatively.
● 4 weeks of coronary revascularization with balloon angioplasty I
IIa
IIb
III

59. Drug Eluting Stents (DES) and Stent Thrombosis
A 2007 AHA/ACC/SCAI/ACS/ADA science advisory report concludes that premature discontinuation of dual antiplatelet therapy markedly increases the risk of catastrophic stent thrombosis and death or MI.
To eliminate the premature discontinuation of thienopyridine therapy, the advisory group recommends the following:
Before implantation of a stent, the physician should discuss the need for dual-antiplatelet therapy. In patients not expected to comply with 12 months of thienopyridine therapy, whether for economic or other reasons, strong consideration should be given to avoiding a DES.
In patients who are undergoing preparation for PCI and who are likely to require invasive or surgical procedures within the next 12 months, consideration should be given to implantation of a bare metal stent or performance of balloon angioplasty with provisional stent implantation instead of the routine use of a DES.

60. Drug Eluting Stents (DES) and Stent Thrombosis
A greater effort by healthcare professionals must be made before patient discharge to ensure that patients are properly and thoroughly educated about the reasons they are prescribed thienopyridines and the significant risks associated with prematurely discontinuing such therapy.
Patients should be specifically instructed before hospital discharge to contact their treating cardiologist before stopping any antiplatelet therapy, even if instructed to stop such therapy by another healthcare provider.
Healthcare providers who perform invasive or surgical procedures and who are concerned about periprocedural and postprocedural bleeding must be made aware of the potentially catastrophic risks of premature discontinuation of thienopyridine therapy. Such professionals who perform these procedures should contact the patient’s cardiologist if issues regarding the patient’s antiplatelet therapy are unclear, to discuss optimal patient management strategy.

61. Drug Eluting Stents (DES) and Stent Thrombosis
Elective procedures for which there is significant risk of perioperative or postoperative bleeding should be deferred until patients have completed an appropriate course of thienopyridine therapy (12 months after DES implantation if they are not at high risk of bleeding and a minimum of 1 month for bare-metal stent implantation).
For patients treated with DES who are to undergo subsequent procedures that mandate discontinuation of thienopyridine therapy, aspirin should be continued if at all possible and the thienopyridine restarted as soon as possible after the procedure because of concerns about late stent thrombosis.