Coronary Artery Stents: Management in Patients Undergoing Noncardiac Surgery
Key points
When managing patients with coronary artery stents in place:
The number of percutaneous coronary interventions (PCIs) performed and the use of coronary artery stents have risen exponentially in the last two decades. While there has been a recent plateau in activity, the total number of patients with coronary artery stents in place continues to increase. The development of newer and more complex antiplatelet drug therapy regimens and the risk of acute stent thrombosis in these patients at the time of noncardiac surgery makes this a challenging area for cardiologist, anaesthetist, surgeon and patient [1].
Percutaneous coronary interventions
The development of coronary angioplasty in the late 1970s heralded a new era in the treatment of coronary artery disease. The subsequent development of coronary artery stents in the 1990s allowed cardiologists to overcome some of the limitations of plain old balloon angioplasty, notably arterial recoil. However, in-stent restenosis remained an issue in approximately 10% of cases and acute stent thrombosis remained a significant risk. The introduction of drug eluting stents did much to reduce restenosis and dual antiplatelet therapy has greatly decreased the incidence of early acute stent thrombosis.
Due to improved access and safety, the number of coronary revascularisation procedures has greatly increased in recent years: coronary artery bypass grafting (CABG) has increased by 50% since 1991 while the number of PCIs performed has increased by eightfold! Percutaneous coronary intervention is now the dominant form of coronary revascularisation, with a ratio of PCI to CABG of 3:1. In 2008 > 230 000 coronary angiograms were performed in the UK, with > 80 000 PCIs in the same year. For the anaesthetist, this means that many more patients undergoing noncardiac surgery will have coronary artery stents in place. The main issue for these patients is the relative risk of acute stent thrombosis and bleeding because of antiplatelet therapy at the time of surgery.
The characteristics of patients who may benefit from PCI are shown in Table 2.1. In patients with ST elevation myocardial infarction (STEMI), the mortality benefits of immediate PCI in comparison with thrombolysis are clear, with an absolute reduction in short-term mortality (4–6 weeks) from 8% to 5%, and a similar reduction in long-term mortality (6–18 months) from 8% to 5%. However, these benefits are time-dependent and if PCI cannot be delivered promptly (within 90–120 min), then immediate thrombolysis should be given with subsequent angiography ± PCI within the next 3–24 h. Thus, in areas remote from a cardiac catheter laboratory, prehospital thrombolysis with subsequent follow-on PCI is likely to remain the reperfusion therapy of choice, with primary PCI for those patients near a cardiac laboratory.
Table 2.1 Patients who may benefit from coronary revascularisation.
| Patient type | Revascularisation choice | Benefit |
| ST elevation myocardial infarction (STEMI) | Immediate (primary) PCI or thrombolysis (if 90–120 min delay for PCI) | Decreased early and late mortality |
| Non-ST elevation myocardial infarction (NSTEMI) | Angiography and PCI within 72 h, or immediately if high risk features (arrhythmia, ongoing pain) | Decreased recurrent MI and readmission to hospital |
| Chronic stable angina (one or two-vessel disease) | Optimal medical therapy ± PCI ± CABG | No mortality benefit but improved symptoms following PCI and CABG |
| Chronic stable angina (left mainstem or three-vessel disease) | Optimal medical therapy ± PCI ± CABG | CABG is superior to PCI in most patients with a mortality benefit. |
PCI: percutaneous coronary intervention; CABG: coronary artery bypass graft; MI: myocardial infarction.
In the context of non-ST elevation myocardial infarction (NSTEMI), PCI decreases the incidence of subsequent cardiac events and readmission to hospital. If patients are stable, then PCI should be performed within 72 h as an inpatient. Unstable patients with heart failure or arrhythmias should be considered for urgent PCI. In patients with chronic stable angina, PCI offers relief of the symptoms of angina in the medium term and decreases the need for anti-anginal drugs. However, elective PCI for chronic stable angina does not confer any mortality benefit. In patients with multivessel coronary artery disease for whom there is a choice between CABG and PCI, CABG is more cost-effective and may offer better outcomes, especially in diabetic patients. However, CABG is more invasive and patient choice may favour PCI. This is especially true in elderly patients with comorbidities, for whom there may be increased risks with CABG.
While there are new types of stent in development, the current major choice is between ‘bare metal’ and ‘drug-eluting’ stents (Table 2.2). There is a range of drugs eluted from stents, but all are essentially antimitotic and are designed to decrease new tissue formation in the luminal surface of the stent (‘neo-intimal hyperplasia’), which in turn decreases the chance of restenosis. The length of time the drug ‘elutes’ varies between stent and drug but ranges from several weeks to several months. Systemic effects have not been reported. Key differences with drug-eluting versus bare metal stents include a decreased incidence of in-stent restenosis, a slight increase in late stent thrombosis due to less complete endothelialisation, and a requirement for a longer period of dual antiplatelet therapy.
Table 2.2 Characteristics of drug-eluting and bare metal stents.
| Bare metal | Drug-eluting (drug) | |
| First used in man | 1994 | 2000 |
| Current examples | Vision | Xience, Promus (Everolimus) |
| Driver | BioMatrix (Biolimus A9) | |
| Express | Taxis (Paclitaxel) | |
| Cypher (Sirolimus) | ||
| Endeavour (Zotarolimus) | ||
| In-stent restenosis rate at 1 year | 5–10% | 0–3% |
| Risk of early stent thrombosis (≤ 1 year) | Depends on clinical scenario: 0.6–3.4% | Depends on clinical scenario: 1.2–3.4% |
| Risk of late stent thrombosis (>1 year) | <0.6% per year | 0.6% per year |
| Cost per stent | ∼£120 | ∼£330 |
The risks of late stent thrombosis lead cardiologists to avoid the use of drug-eluting stents in proximal lesions, for which stent thrombosis is more likely to be fatal, or in large vessels in which a degree of restenosis is less likely to be clinically relevant. A recent study has demonstrated little clinical difference between bare metal and drug-eluting stents in this clinical situation, although this remains an area of emerging evidence [2].
Newer technologies under development include bio-absorbable stents, which may in the future offer an elegant solution to the lifelong risk of acute stent thrombosis, although trials are at an early stage.
Radial or femoral access
In recent years, the radial artery has become the preferred route of access to the coronary arteries for PCI, and has several advantages, including increased patient comfort, earlier mobilisation, less bleeding due to easier compression of artery, and a decreased incidence of major complications, i.e. a 0.5% incidence of major complications as opposed to a 1.2% incidence with femoral access. In some patients, there is transient loss of the radial pulse after the procedure but most patients can have subsequent repeat procedures via the radial route. In about 5% of patients, an absent radial artery or extreme tortuosity makes this access route impossible and femoral access is required.
Antiplatelet and anticoagulant therapy
Before PCI
If possible, patients are routinely pretreated with oral aspirin (300 mg loading dose; 75 mg once daily thereafter) and a second antiplatelet agent, most commonly clopidogrel (300–600 mg loading dose; 75 mg once daily thereafter). Newer antiplatelet therapies are coming to market with different profiles in terms on onset and offset of action.
During PCI
There are several additional antiplatelet and anticoagulant therapies that can be used alone or in combination during PCI depending on the clinical situation (Table 2.3). Each cardiac lab will have its own preferences for the agents used but, needless to say, while these strategies may improve outcomes for patients, they also increase the risk of bleeding, which may be a significant issue in a patient undergoing surgery.
Table 2.3 Additional anticoagulant and antiplatelet drugs used in association with percutaneous coronary interventions.
| Unfractionated heparin | |
| Low molecular weight heparin | Enoxaparin (Clexane) |
| Factor Xa inhibitor | Fondaparinux (Arixtra) |
| ‘Reversible’ IIb/IIIa inhibitors | Tirofiban (Aggrastat) |
| Eptifibatide (Intergrillin) | |
| ‘Irreversible’ IIb/IIIa inhibitors | Abciximab (Reopro) |
| Reversible direct thrombin inhibitor | Bivalirudin (Angiomax) |
Longer-term oral antiplatelet therapy
All patients should receive dual antiplatelet therapy after coronary artery stenting. This will usually comprise aspirin 75 mg daily and a thienopyridine (usually clopidogrel 75 mg), although newer antiplatelet therapies are emerging on the market. The duration of dual antiplatelet therapy will depend upon the clinical context of the stenting procedure (up to 12 months after myocardial infarction) and the type of stent used (four-week minimum for bare metal stents and up to 12 months for drug-eluting stents). The position of the stent may also influence the duration of treatment, with some cardiologists preferring lifelong, dual antiplatelet therapy in patients who have a left mainstem stent or proximal left anterior descending artery stents due to the potential catastrophic result of acute stent thrombosis in these patients compared with more distal stent placement.
Early discontinuation of dual antiplatelet therapy is associated with a greatly increased risk of acute stent thrombosis. There is high mortality (up to 40%) if surgery is performed with four weeks of coronary stenting. Clearly, early discussion with a cardiologist, and ideally the cardiologist involved in the original PCI, is desirable if antiplatelet therapy is changed.
Stenting and warfarin
In general, if warfarin is prescribed for primary prevention of thrombo-embolism due to atrial fibrillation, it can be discontinued during the immediate post-stenting period while dual antiplatelet therapy is prescribed. In these patients, bare metal stents may be advantageous in that they allow more rapid and complete stent endothelialisation. The management of patients taking warfarin for metal prosthetic heart valves or recurrent life-threatening embolism is more challenging. In these circumstances, the risks of bleeding and acute stent thrombosis should be assessed on a case-by-case basis. In general, warfarin may be discontinued before the procedure to decrease the risk of access site complications (often ‘covered’ with unfractionated or low molecular weight heparin) but restarted along with dual antiplatelet therapy immediately after stenting. The duration of the concomitant prescription of warfarin and dual antiplatelet therapy requires careful consideration because of the greatly increased risks of bleeding, especially in elderly patients. Early discussion with a cardiologist is advised if these patients require surgery in the early post-stent period.
Coronary artery stenting and noncardiac surgery
In general, coronary angioplasty should be avoided before elective surgery: there is no evidence to support the revascularisation of stable patients in advance of surgery and indeed, as noted above, the risks to patients during noncardiac surgery immediately after coronary stenting are very high. If stenting has been performed, then elective surgery should be avoided in the post-stenting period because of the increased risk of acute stent thrombosis and myocardial infarction in the perioperative period. In a recent study, the risk of perioperative death or ischaemic event after noncardiac surgery was 42% in patients who had had a coronary stent placed within 42 days before noncardiac surgery. This happened in only 13% of patients who had coronary artery stenting before this period [2].
Elective surgery after stenting
When stenting is required to treat either STEMI, ischaemic cardiac pain at rest or significant symptoms with evidence of reversible myocardial ischaemia, then surgery should be delayed if possible until endothelialisation of the stent occurs. If planned procedures cannot be delayed, e.g. cancer surgery, then the preferential use of bare metal stents will result in more rapid and complete stent endothelialisation – within about four weeks – compared with drug eluting stents, which can take up to 12 months to endothelialise.
Urgent surgery after stenting
In situations in which emergency major surgery is required in the early post-stent period, close communication between cardiologist, anaesthetist and surgeon is required to balance the risks of bleeding and acute stent thrombosis. If at all possible, dual antiplatelet therapy, and at the very least aspirin, should be continued. The risk of significant surgical bleeding is increased by about 50% for patients on dual antiplatelet therapy, although there does not appear to be increased mortality associated with this [3]. If the second antiplatelet drug (usually clopidogrel) is stopped, then this should be discontinued for as short a time as possible. Given that clopidogrel is an irreversible binder to platelets, it should be stopped five days before surgery and restarted as soon after surgery as is judged safe. One of the newer antiplatelet therapies, ticagrelor, is reported to have a shorter half-life and may offer a slight advantage in the future over clopidogrel when more rapid reversal of antiplatelet effect is required. If this situation occurs in the early post-stent period then bridging therapy with heparin, a short acting antiplatelet, e.g. tirofiban, or direct thrombin inhibitor, e.g. bivalirubin, may be considered, although there is little evidence to support this approach.
Management of complications in patients with stents
The most serious complication is acute stent thrombosis. This is often due to underdeployment of stents with a lack of stent strut apposition to the vessel wall or interruption of dual antiplatelet therapy. A clinical risk coring system has been described that estimates the incidence of this complication (Table 2.4) [4]. The use of adjunct technologies such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can decrease the risk of stent underdeployment and thus result in a lower incidence of acute stent thrombosis and restenosis (Table 2.5).
Table 2.4 Clinical risk score for prediction of stent thrombosis [4].
| Clinical factor | Hazard ratio* | Weighted score |
| Thienopyridine discontinuation <6 months after stent | 5.28 | 5 |
| Insulin-treated diabetes | 4.74 | 5 |
| Left mainstem stenting | 2.73 | 3 |
| Smoker | 2.63 | 3 |
| Lesion length >28 mm | 2.35 | 2 |
| Multiple stenting | 2.25 | 2 |
| Moderate to severe lesion calcification | 2.25 | 2 |
| Reference diameter <3 mm | 1.72 | 2 |
| Total possible score | 24 | |
| Risk stratification | ||
| Low risk; % | 0–6 (0.8%) | |
| Medium risk; % | 7–13 (3.6%) | |
| High risk; % | 14–24 (12.6%) |
*Hazard ratio describes the increased risk, i.e. a Hazard ratio of 2 describes a 2 fold increase in the risk of the event occurring.
Table 2.5 Adjunct technologies in percutaneous coronary intervention.
| Technology | Availability | Use |
| Intra-aortic balloon pump | Widespread | Haemodynamic support in patients with critical myocardial ischaemia or cardiogenic shock |
| Intravascular Ultrasound (IVUS) | Widespread | Gives details of vessel size. Excellent images of stents, particularly useful in guiding post-dilatation or in acute stent thrombosis |
| Pressure wire / FFR | Widespread | Measures pressure within the coronary artery. When coupled with adenosine challenge, can give measure of functional significance of a lesion |
| Rotablation | Widespread | Used to debulk coronary arteries before stenting |
| Laser | Limited | Used to debulk coronary arteries before stenting |
| Brachytherapy | Limited | Use of radiation therapy for the treatment of recurrent in-stent restenosis |
| Optical Coherence Tomography (OCT) | Emerging technology | Uses light rather than ultrasound – excellent visualisation of intra-arterial structure and stents but poor tissue penetration |
Acute stent thrombosis
This complication has a 20–40% mortality, and is often due to a mechanical problem with the stent such as malapposition of a stent strut or strut fracture. Its management can be very challenging in the immediate postoperative period after major surgery, when life-threatening bleeding can readily occur. The following steps are recommended:
Minor bleeding after surgery
Major bleeding after surgery
Clearly, this is an area in which close communication between cardiologist, anaesthetist and surgeon is required. The balance of risks will be between life-threatening bleeding and acute stent thrombosis, which both carry a high mortality.
Adjunct technology and future developments in coronary stenting
Stent design is becoming increasing complex. The stents themselves are increasingly ‘deliverable’ to tortuous arteries, resulting in increased procedural success. Technologies such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS) permit the visualisation of the stents to ensure that deployment is optimised, which decreases the incidence of complications such as acute stent thrombosis and restenosis. Newer stent technology allows abluminal drug delivery with cytotoxic agents to decrease the risk of restenosis while the abluminal stent surface attracts endothelial progenitor cells with antibodies to encourage early re-endothelialisation of stent struts. In certain situations, these ‘genus’ stents may be advantageous, allowing surgery to be performed sooner (at about two weeks) after stenting because of rapid endothelialisation. The development of completely bio-absorbable stents may offer an elegant solution to the risks of late stent thrombosis, although their efficacy will have to be tested.
Aspirin and clopidogrel resistance
It is increasingly recognised that not all patients gain the same benefit in terms of antiplatelet effect from aspirin and clopidogrel. Several blood tests are available that measure platelet function but their current usefulness in directing clinical practice is unproven. These tests include impedance aggregometry, platelet function analysis and thrombo-elastography [5]. However, there remains poor correlation between measured platelet function and perioperative bleeding or stent thrombosis, and further work is clearly required in this area. Nevertheless, it appears that aspirin resistance may be more common in patients with diabetes, although until there is a better clinical test, diabetics should continue to receive the same antiplatelet therapy as nondiabetics.
Conclusions
Percutaneous coronary intervention has revolutionised the treatment of patients with coronary artery disease, offering significant benefits in terms of both mortality and morbidity. The widespread use of coronary stents has resulted in dramatic improvement in procedural success and has decreased the need for emergency CABG. While revascularisation may decrease surgical risk in unstable patients, in other patients with previous stenting there is a risk of acute stent thrombosis at times of intercurrent illness or surgery. Close communication is required between anaesthetist, cardiologist, surgeon and the patient to ensure that care is tailored to the individual patient to minimise the risks of acute stent thrombosis and bleeding at the time of surgery.
References
1. Grines, C.L., Bonow, R.O., Casey, D.E., et al. (2007) Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons and American Dental Association, with representation from the American College of Physicians. Circulation, 115, 813–818.
2. Cruden, N.L., Harding, S.A., Fapan, A.D., et al. (2010) Previous coronary stent implantation ans cardiac events in patients undergoing noncardiac surgery. Circulation: Cardiovascular Interventions, 3, 236–242.
3. Chassot, P.G., Delabays, A. & Spahn, D.R. (2007) Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. British Journal of Anaesthesia, 99, 316–328.
4. Baran, K.W., Lasala, J.M., Cox, D.A., et al. (2009) A clinical risk score for prediction of stent thrombosis: the Dutch Stent Thrombosis Registry. Journal of the American College of Cardiologists, 53, 1399–1409.
5. Llau, J.V., Ferrandis, R., Sierram, P. & Gomez-Luque, A. (2010) Prevention of the renarrowing of coronary arteries using drug-eluting stents in the perioperative period: an update. Vascular Health and Risk Management, 6, 855–867.