Patients with drug-eluting stents (DES) pose a particular
dilemma in the perioperative period. Current recommendations include
delaying noncardiac surgery until the course of dual anti-platelet therapy is
complete. Based on current clinical and
autopsy findings, it is unclear how long dual anti-platelet therapy must
continue to prevent late stent thrombosis. It is clear, though, that patients must remain on
aspirin forever. This scenario is
particularly challenging to us as anesthesia providers, as there are no guidelines
currently to manage these patients perioperatively. The perioperative period is
especially problematic because 1) surgery induces a hypercoagulable state; 2)
surgeons often stop aspirin +/- clopidogrel preoperatively to minimize the risk
of surgical bleeding, but without consulting their patients' cardiologists; and
3) there is a high likelihood that the DES are not yet endothelialized. Thus,
each DES patient, if stent thrombosis occurs, has a 45% chance of dying
perioperatively. There are 3 points to consider: 1) transition of dual
anti-platelet therapy in the perioperative period; 2) returning patients to
their regimen as soon as possible postoperatively; 3) maintaining these
patients on aspirin throughout the entire perioperative period, since perioperative
ST-segment elevation myocardial infarction (STEMI) and death have been
associated with the discontinuation of aspirin in these patients.10
We collaborated with the interventional cardiologists at
Wake Forest University Health Sciences to develop a strategy to best manage
these patients. Our protocol includes utilizing both eptifibatide
(Integrilin, a GP IIb/IIIa inhibitor) and heparin as "bridging
therapy" to prevent stent thrombosis in the perioperative period. Both medications are necessary in order to 1)
prevent platelet activation and adhesion (eptifibatide) and 2) prevent thrombin
formation (heparin), which again causes platelet activation and clot formation.
Both eptifibatide and heparin have short half-lives, necessitating these drugs
to be given as intravenous infusions. Further, both drugs can be
stopped 6 hours prior to surgery with
complete return of platelet function and coagulation. Cooperation between
anesthesiology, cardiology, and surgery are of the utmost importance. The
surgeon may elect to proceed with surgery while the patient remains on
clopidogrel and aspirin. Alternatively, if the surgeon feels that perioperative
clopidogrel will be deleterious in terms of increased surgical bleeding, then
the following protocol will be instituted:
1. The
following information must be obtained from the patient's cardiologist:
a. Type(s) of DES placed and date of procedure
b. any complexities associated with stent placement
(bifurcations, coronary vessel diameter, total stent length)
c. comorbidities: renal failure, diabetes,
depressed ejection fraction.
2. Clopidogrel is discontinued 5 days prior to surgery (a cardiology consult should be obtained prior to discontinuation of clopidogrel).
3. Aspirin must be continued throughout the perioperative period.
4. The patient will be admitted to the appropriate surgical service
2 days prior to surgery to receive bridging therapy (eptifibatide and heparin)
and prevent stent thrombosis.
5. The bridging therapy will be initiated
according to the paradigm shown in Table 1.
6. IV eptifibatide and heparin infusions
will be discontinued 6 hours prior to surgery to 1) facilitate normal
intraoperative platelet function and coagulation, and 2) allow for regional
anesthetic techniques to be performed preoperatively.
7. Upon agreement between cardiology
and surgery, clopidogrel/eptifibatide will be readministered as soon as
possible postoperatively (preferably, the postoperative night):
a. clopidogrel loading dose: 600 mg p.o.
b. clopidogrel maintenance dose: 75 mg
p.o. daily
3. eptifibatide infusion will be restarted
according to the above paradigm if clopidogrel cannot be reinitiated.
In conclusion, DES represents the most current therapy in interventional cardiology. However, late stent thrombosis is a major problem with these devices. In fact, the FDA has recently reviewed the safety of these devices, and new recommendations regarding dual anti-platelet therapy may be forthcoming. By utilizing a combination of eptifibatide, heparin, and aspirin, the risk of stent thrombosis will be markedly reduced in the perioperative period. However, we will continue to address and modify our therapeutic approach as the dynamic nature of this subject continues to evolve. This is an important patient safety issue because of the high mortality rate if stent thrombosis occurs.
http://www.apsf.org/resource_center/newsletter/2007/winter/12_protocol.htm