Peri-Operative Management
of Drug Eluting Stents
Stephen T. Thew, MD, FACC
Heart Clinics Northwest
Balance
Bleeding
Stent Thrombosis
Outline/Highlights

Timing of elective surgery

What to do with medications
• Stopping anti-platelet meds
• When to restart

Post operative concerns
Timing of Surgery Post-Stenting

Bare Metal Stents
• Wait 30-45 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 (??)
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 300-600mg bolus

REALLY try to continue aspirin, if stopped
do so 5 days before and restart ASAP
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
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
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
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
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
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?
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?

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
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
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
Brief history of Coronary Revascularization
Limitations to PTCA
Complications
•
•
•
•
Acute vessel closure
Dissection
Intra-coronary thrombus
Emergent CABG
Durability
• Restenosis
• Elastic Recoil
• Intimal Hyperplasia
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
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
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
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 neointimal growth

Restenosis rates dropped to around 4-5%
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
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
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
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
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
Stent Thrombosis

Post surgery rise in thrombogenic risk
- increased catecholamine release
- increased platelet aggregation
- decreased fibrinolysis
Stent Thrombosis

Discontinuation of aspirin leads to a
‘rebound’ effect
Anti-Platelet Agents
in Addition to Aspirin
Oral
•
•
•
•
Ticlid
Plavix
Effient
Brilinta
IV
• ReoPro
• Integrlin
• Aggrastat
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
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
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
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
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
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
Bleeding Risk with Surgery

Burger, et al – 49,000+ patients

Stopping aspirin had higher cardiac,
cerebral and peripheral vascular events
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
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
Surgical Risk and Timing

At > 1 year since PCI the risk
approximates that of a intermediate nonrevascularized patient with 1 or 2 clinical
risk factors
Wijeysundera, et al
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
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
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
Strategies for Peri-op Management of DES
URGENT SURGERY
•
Urgent-Emergent surgeries have 4-fold higher
mortality
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).
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
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
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
Summary/Highlights

Timing of elective surgery

What to do with medications
◦ Stopping anti-platelet meds (DAPT)
◦ When to restart

Post operative concerns
Timing of Surgery Post-Stenting

Bare Metal Stents
• Wait 30-45 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 (??)
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 300-600mg bolus

REALLY try to continue aspirin, if stopped
do so 5 days before and restart ASAP
Anti-platelet medications

Consider “bridging therapy” with IV
administration of IIb/IIIa inhibitor (short
half-life) in certain situations
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
Proposed Approach to the Management of
Patients with Previous PCI Who Require
Noncardiac Surgery
Previous PCI
Balloon
angioplasty
Drug-eluting
stent
Bare-metal
stent
<365 days
Time since PCI
<14 days
Delay for elective or
nonurgent surgery
PCI, percutaneous coronary intervention
>14 days
>30- 45 days
Proceed to the
operation room
with aspirin
<30- 45 days
Delay for elective or
nonurgent surgery
>365 days
Proceed to the
operating room
with aspirin
Proposed Treatment for Patients Requiring
PCI Who Need Subsequent Surgery
Acute MI, H risk ACS, or
H risk cardiac anatomy
Bleeding risk of surgery
low
Stent & continue dual
antiplatelet therapy
Not low
Timing of surgery
14-29 days
Balloon
angioplasty
30-365 days
Bare-metal
stent
>365 days
Drug-eluting
stent
Thank you
Preoperative Coronary Revascularization With
CABG or Percutaneous Coronary Intervention
Coronary revascularization before noncardiac
surgery is useful in patients with stable angina
who have:
I IIa IIb III
● 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
Preoperative Coronary Revascularization With
CABG or Percutaneous Coronary Intervention
I IIa IIb III
I IIa IIb III
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.
Preoperative Coronary Revascularization With
CABG or Percutaneous Coronary Intervention
The usefulness of preoperative coronary
revascularization is not well established in:
I IIa IIb III
High risk ischemic patients (e.g. abnormal
dobutamine stress echo with at least
5 segments of wall-motion abnormalities)
I IIa IIb III
Low risk ischemic patients with an
abnormal dobutamine stress echo
(segments 1-4)
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
I IIa IIb III
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
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.
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.
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.