Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Patricia A Pellikka, MD, FACC, FAHA, FASE
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INTRODUCTION — The management of antiplatelet therapy in patients who need noncardiac surgery after percutaneous coronary intervention (PCI) with stenting requires consideration of the competing risks of acute coronary events with premature cessation and bleeding with continuation of antiplatelet therapy. This is an important clinical problem, as it is estimated that about 5 to 10 percent of patients with coronary stents undergo noncardiac surgery within one year of stent implantation [1-5].
This topic will focus on the approach to patients scheduled to undergo elective noncardiac surgery after PCI with stenting and who are taking dual antiplatelet therapy. Patients who require urgent or emergent surgery or those who receive balloon angioplasty are also discussed briefly. The approach to antiplatelet therapy in patients scheduled for coronary artery bypass graft surgery is presented separately. (See "Medical therapy to prevent complications after coronary artery bypass graft surgery", section on 'Preoperative aspirin' and "Medical therapy to prevent complications after coronary artery bypass graft surgery", section on 'Platelet P2Y12 receptor blocker therapy'.)
The larger discussion of the risk of coronary artery stent thrombosis, one of the potential complications of discontinuing antiplatelet therapy prior to noncardiac surgery, is found elsewhere. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients" and "Coronary artery stent thrombosis: Incidence and risk factors".)
DEFINITIONS — For this topic, major surgery is defined as any surgery for which the surgeon might recommend the discontinuation of dual antiplatelet therapy due to a concern for an increase in bleeding risk. Most studies that have evaluated this issue have included patients scheduled to undergo peripheral arterial, orthopedic, abdominal, or thoracic surgery, or radical prostatectomy, nephrectomy, or cystectomy.
Adverse perioperative outcomes include acute coronary syndromes (including myocardial infarction), death, urgent revascularization, and bleeding. In some studies, stent thrombosis is included as an outcome; stent thrombosis is often the proximate cause of myocardial infarction or death.
COMPLICATIONS — For patients taking dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) who need to undergo noncardiac surgery, the risk of perioperative adverse cardiac events such as myocardial infarction (MI), death, stent thrombosis, and the need for urgent repeat revascularization is related in large measure to the premature cessation of DAPT, the prothrombotic state created by the surgery, or an interaction between the two. Perioperative bleeding associated with the continuation of DAPT is also associated with an increased risk of perioperative cardiac events.
Observational studies suggest that patients who have undergone noncardiac surgery within six weeks after stenting may have an increased risk of death or MI [6-8]. These events are often due to stent thrombosis, which may be caused by the premature discontinuation or reduction of antiplatelet therapy, the thrombotic risk associated with many forms of major surgery, or an interaction between the two. Stent thrombosis can lead to high rates of myocardial infarction percent (50 to 70 percent) and death (10 to 40 percent), both of which are included as components of composite outcomes in the studies discussed below . (See 'Timing, incidence, and clinical predictors' below.)
Premature cessation of antiplatelet therapy — In patients taking aspirin and a platelet P2Y12 receptor blocker after PCI, the premature cessation of one or both agents is associated with an increase in adverse events such as stent thrombosis, MI, or death. In fact, the premature cessation of dual antiplatelet therapy (and in particular the P2Y12 receptor blocker) is the strongest predictor of stent thrombosis. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Risk factors'.)
Prothrombotic and proinflammatory effects of surgery — The prothrombotic and proinflammatory effects of surgery may predispose the coronary circulation to thrombosis, both at the site of prior stent placement and at other sites of atherosclerotic lesions [10-13]. The perioperative prothrombotic state may be mediated by increased platelet aggregation and decreased fibrinolysis [14-16].
Incomplete strut coverage — Incomplete strut coverage early after stent implantation is a risk factor for adverse outcome. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis'.)
Timing, incidence, and clinical predictors — Multiple observational studies have evaluated the timing, incidence, and clinical predictors of adverse outcomes in stented patients undergoing noncardiac surgery. They have shown that patients who undergo major noncardiac surgery within six weeks, and particularly within two weeks, of PCI with bare-metal (BMS) or drug-eluting stents (DES) have an increased risk of adverse cardiovascular events [1,4,6-8,17-19]. This increased risk extends for as long as 12 months after DES placement. Findings from the following four large studies are representative.
In a case-control study of 24,313 patients who underwent noncardiac surgery (1120 stented patients), the following findings were noted :
●The 30-day rates of major adverse cardiac and cerebrovascular events (death, MI, cardiac arrest, or stroke) were 3.7 and 1.5 percent in stented and unstented patients (p<0.001).
●The risk was related to the time from stent implantation to surgery, with a significantly elevated risk during the first year (adjusted odds ratio 2.59, 95% CI 1.36-4.94.
●The risk was increased in patients with drug-eluting and bare metal stents.
In a retrospective cohort study of 28,029 individuals (41,989 operations) who underwent noncardiac surgery within 24 months of stent implantation, the following was noted :
●The rate of major adverse cardiac events (MACE), a combination of all-cause mortality, MI, and cardiac revascularization, was 4.7 percent at 30 days.
●The time between stenting and surgery was associated with MACE (<6 weeks, 11.6 percent; 6 weeks to <6 months, 6.4 percent; 6 to 12 months, 4.2 percent; >12 to 24 months, 3.5 percent). Thus, rates appeared to stabilize after six months; there was only a minor decrease in the risk of MACE between 6 and 12 months.
●The factors most strongly associated with MACE were nonelective surgical admission (adjusted odds ratio [AOR] 4.77), history of MI in the six months preceding surgery (AOR 2.63), and revised cardiac risk index (table 1) >2 (AOR 2.13).
●The rate of MACE was 5.1 percent for BMS and 4.3 percent for DES (p<0.001). The odds of MACE for surgery between six weeks and six months were actually lower for DES with no difference before six weeks or after six months.
●In a nested case-control study comparing 284 patients with confirmed MACE who had surgery >6 weeks after stenting with matched pairs who were free of MACE, the likelihood of completely stopping all antiplatelet therapy for at least five days was similar (22.9 versus 25.4 percent). Of note, patients with surgery followed by death as the only MACE event were excluded. Given multiple issues with confounding, we do not believe these data are compelling enough to suggest it is safe to discontinue all antiplatelet therapy prior to surgery. (See 'Summary and recommendations' below.)
In a cohort study of 8116 patients who underwent intermediate-to-high-risk elective noncardiac surgery and received coronary stents within 10 years before surgery (about one-third were within two years), the following were noted :
●For the 8116 surgical patients who underwent PCI within 10 years, the primary outcome (30-day composite of mortality, readmission for acute coronary syndrome, or repeat revascularization) occurred in 2.1 percent. This rate was comparable to that of intermediate risk individuals who had never received PCI. Intermediate risk was defined using the Revised Cardiac Risk Index . (See "Evaluation of cardiac risk prior to noncardiac surgery", section on 'Revised cardiac risk index'.)
●When the interval between stent placement and surgery was less than 45 days, the event rates for BMS and DES were very high at 6.7 and 20.0 percent respectively. Comparing these patients operated on during this time interval to those whose surgery was at least two years after PCI, the AOR for 30-day events was 2.35, 95% CI 0.98-5.64 and 11.58, 95% CI 4.08-32.80, respectively.
●When the interval was 45 to 180 days, the event rates for BMS and DES were 2.6 and approximately 4 percent, respectively. The adjusted OR were 1.06, 95% CI 0.58-1.92 and 1.71, 95% CI 0.73-4.01, respectively.
●When the interval was 181 to 365 days, the event rate for DES was 1.2 percent (adjusted OR 0.64, 95% CI 0.20-2.04). Surprisingly, the event rate for BMS increased to about 3.5 percent during this time period, perhaps due to an increased rate of restenosis with BMS.
In a retrospective Veterans Affairs (United States) cohort study of patients treated with coronary stents, outcomes in 20,590 patients who underwent noncardiac surgery within 24 months of stent placement were compared to those in 41,180 nonsurgical patients . The following findings were noted:
●Within 30 days after surgery, the surgical cohort had higher rates of the composite end point of MI and/or cardiac revascularization compared with nonsurgical patients at a similar time interval from stent placement (3.1 versus 1.9 percent; risk difference 1.3 percent, 95% CI 1.0-1.5).
●The risk difference (incremental risk for surgery) was 3.5 percent immediately following stenting, 2.8 percent during the first six weeks, 2.0 percent between six weeks and six months, and fell to about 1 percent at six months, after which the risk difference seemed to remain stable .
The following observations regarding the timing and incidence of adverse outcomes following the premature discontinuation of antiplatelet therapy in patients not undergoing surgery also help inform our recommendations for managing antiplatelet therapy in patients who require noncardiac surgery:
●In patients with stable coronary artery disease, aspirin is recommended indefinitely to prevent recurrent cardiovascular events and discontinuation of aspirin has been estimated to be responsible for at least 15 percent of all recurrent events in this population [23,24]. (See "Perioperative medication management", section on 'Aspirin' and "Aspirin for the secondary prevention of cardiovascular disease".)
●Most cases of stent thrombosis occur within the first 30 days after placement, irrespective of stent type. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Timing and incidence'.)
The importance of the continuation of antiplatelet therapy in the perioperative period was evaluated and confirmed in a multicenter, retrospective study of 666 patients with prior coronary stenting who subsequently underwent cardiac or non-cardiac (86 percent) surgery . Of these, 371 (55.7 percent) discontinued all or part of their antiplatelet therapy (aspirin, clopidogrel, or both) ≥5 days before surgery. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (MACE), a combination of cardiac death, myocardial infarction, or stroke, and the primary safety end point was 30-day Bleeding Academic Research Consortium (BARC) bleeding ≥2 (table 2). The overall mean time from PCI to surgery was about 500 days and the mean time from discontinuation of antiplatelet therapy to surgery was five days. Among those who discontinued some antiplatelet therapy, approximately 10 percent remained on aspirin. Comparing those who discontinued therapy to those who did not, the following findings were noted:
●The rate of MACE was higher (7.5 versus 0.3 percent; p = 0.027)
●After adjustment, perioperative antiplatelet discontinuation was the strongest independent predictor of MACE (odds ratio [OR] 25.8, 95% CI 3.37-198).
●Continuation of aspirin was associated with a significantly lower risk of MACE (adjusted OR 0.27, 95% CI 0.11-0.71).
●After adjustment, there was no significant difference in the rate of the safety end point
As mentioned above, premature cessation of DAPT is the major predictor of stent thrombosis, irrespective of stent type. The risk has been estimated to be 30- to 50-fold or greater. In patients who stop both agents, stent thrombosis generally occurs within 10 days in the majority of patients who develop this complication. (See "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Early and late stent thrombosis' and "Coronary artery stent thrombosis: Incidence and risk factors", section on 'Timing and incidence' and "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Drug-eluting stents'.)
Bleeding — The risk of a serious complication related to perioperative bleeding in patients taking one or two antiplatelet agents is not well studied, except in patients undergoing coronary artery bypass graft surgery (CABG). In these patients, preoperative dual antiplatelet therapy increases that rate of bleeding as well as the need for reoperation and transfusion. Given concerns for the need for reoperation, discontinuation of P2Y12 receptor blocker at least five days (or seven days for prasugrel) before surgery is recommended. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Bleeding'.)
For non-CABG surgical patients, aspirin alone or with P2Y12 receptor blocker increases the risk of bleeding by as much as 20 and 50 percent, respectively, and these rates are dependent on the location of the surgery [26,27]. This excess bleeding leads to an increase in red blood cell transfusion, but not to an increase in surgical mortality or morbidity.
Despite the lack of definitive evidence of an increase in surgical mortality or morbidity in patients taking dual antiplatelet therapy, many surgeons recommend discontinuing P2Y12 receptor blocker before surgery. In some situations such as neurosurgery, where the consequence of bleeding might be catastrophic, both aspirin and P2Y12 therapy are stopped.
OUR APPROACH — The following discussion applies to patients scheduled to undergo noncardiac surgery who have undergone percutaneous coronary intervention (PCI) with stenting within one year. In such patients, it may be necessary to stop one or both antiplatelet agents prior to our recommended duration of such therapy (one year) or even prior to the minimum required duration of treatment with dual antiplatelet therapy (DAPT) for the general population, which is a minimum of one month after bare metal stents (BMS) and for at least six months after drug-eluting (DES). We acknowledge that with second generation DES, it is likely that the difference between in the minimum duration for BMS and DES is less. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Summary and recommendations'.)
We believe that our recommendations (below) for the management of these patients are based on low-quality evidence . Our recommendations for the timing of surgery are based on observations presented above regarding the rates of stent thrombosis in patients with premature cessation of DAPT and rates of adverse cardiovascular events found in studies of patients undergoing noncardiac surgery. (See 'Timing, incidence, and clinical predictors' above.) No randomized trials comparing different times for surgery after PCI or differing antiplatelet strategies have been performed. These recommendations attempt to take into account what is known about the risk of perioperative bleeding on one or two antiplatelet agents.
The use of DAPT should be made on a case-by-case basis, taking into account the relative benefits and risks of continuing such therapy . Prior to surgery, the patient, primary care physician, cardiologist, anesthesiologist, and surgeon should be involved in decision making.
An occasional patient may be scheduled for both elective noncardiac surgery and PCI. It is critically important for all managing physicians to discuss the optimal timing of each procedure. Prior to a decision for PCI and selection of PCI strategy, the timing and need for noncardiac surgery should be considered. Given the balanced risks of discontinuation of DAPT and proceeding with surgery despite DAPT, the first critical decision is the absolute need for PCI. As in other situations, a decision for appropriate PCI should be based on evidence of clinically significant ischemia and size of the territory at risk and not on angiographic findings alone. Once this decision is made, consideration should be given to choosing "plain old" balloon angioplasty (POBA) rather than stenting; BMS are preferred to DES during this interval. (See 'Timing, incidence, and clinical predictors' above.) In cases where PCI cannot be deferred and noncardiac surgery is urgent (<30 days), POBA may be reasonable to avoid risk of stent thrombosis or absolute requirement for DAPT, as long as a successful result is obtained. Recommendations for minimum DAPT prior to noncardiac surgery according to stent type or after POBA are included in the sections below. (See 'Patients with prior balloon angioplasty' below.)
Elective noncardiac surgery in stented patients — For patients who have undergone stenting with either BMS or DES and who will need cessation of one or both antiplatelet agents, we defer elective noncardiac surgery until after the recommended duration (one year) of DAPT. Prior to this time, and particularly during the first 6 months after stenting, the risk of a cardiovascular event is much higher for stented than nonstented patients. The risk is very high during the first 4 to 6 weeks after stenting. For patients who cannot wait one year, our recommended minimal duration of DAPT is 30 days and six months, for BMS and DES respectively. This issue is discussed elsewhere. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Bare metal stents'.)
It should be kept in mind that there is no high quality evidence to suggest that BMS are a better choice than second generation DES for patients who require noncardiac surgery between 6 weeks and 6 months of PCI (see 'Timing, incidence, and clinical predictors' above). Thus, some or our experts are comfortable allowing elective noncardiac surgery as soon as 4 to 6 weeks after placement of a newer generation DES.
For patients who must undergo noncardiac surgery before they have completed one year of DAPT, the optimal duration of treatment (prior to noncardiac surgery) is not known. The proinflammatory and prothrombotic risks of surgery may increase the baseline risk of stent thrombosis even in the presence of DAPT if a significant percent of struts are not endothelialized. In addition, one cannot predict the possibility that DAPT might have to be stopped due to unexpected major bleeding. Thus, we recommend caution in performing elective noncardiac surgery prior to the recommended duration of such therapy. Although the minimal duration of such therapy is 30 days for BMS, we attempt to continue it for four to six weeks given our concerns about the possible increased risk of stent thrombosis in the perioperative period. There are no randomized trials that have compared 30 days with somewhat longer periods such as six weeks.
One observational study of 8116 patients who underwent major elective noncardiac surgery within 10 years found that the rate of the primary outcome (30-day major adverse cardiac events [mortality, readmission for acute coronary syndrome, or repeat coronary revascularization]) occurred in 6.7 percent in patients operated on before 45 days, compared with 2.6 percent when the interval was 45 to 180 days .
The final decision to continue or discontinue antiplatelet therapy in the perioperative period should be made only after an informed discussion among the surgeon, managing cardiologist (and other health care providers), and the patient has taken place. Some surgeons are not fully aware of the risk of prematurely discontinuing antiplatelet therapy in patients with recent PCI with stenting. In many cases, DAPT can be continued in the perioperative period, although for some surgeries such as neurosurgery, posterior eye surgery, or prostatic surgery, the risk of major bleeding may be greater than the risk of stent thrombosis.
In these patients who undergo noncardiac surgery before one full year of DAPT, a platelet P2Y12 receptor blocker should be discontinued for as brief a period as possible. Aspirin should be continued through the perioperative period, since the risk of stent thrombosis is further increased with the cessation of both aspirin and clopidogrel and surgery can usually be safely performed on aspirin. (See "Perioperative medication management", section on 'Aspirin'.)
Additional points to consider include:
●Minor surgical and dental procedures usually do not require cessation of antiplatelet therapy
●Clopidogrel, prasugrel, and ticagrelor should be stopped five, seven, and three to five days, respectively, before surgery. Some experts are willing to recommend shorter discontinuation periods, for procedures less likely to be associated with major bleeding.
●Clopidogrel, if stopped, should be restarted with a loading dose of 300 mg as soon as possible after surgery, perhaps even later in the day if postoperative bleeding has stopped. Some experts recommend a higher loading dose of 600 mg to decrease time to effectiveness in the higher-risk postoperative setting .
●We suggest that surgery be performed in centers with 24-hour interventional cardiology coverage . (See "Management of cardiac risk for noncardiac surgery", section on 'Revascularization before surgery'.)
Urgent or emergent noncardiac surgery — For patients who require surgery prior to the minimal duration of DAPT discussed above, such as those who require urgent or emergent noncardiac surgery, two issues need to be discussed among all managing practitioners:
●The relative risks and benefits of continuing DAPT
●Role of platelet transfusion. For patients who are at increased risk of bleeding, there will not be time to discontinue one or both antiplatelet agents. While platelet transfusion may be necessary for excessive bleeding after surgery, the role of prophylactic platelet transfusion has not been well studied. (See "Congenital and acquired disorders of platelet function", section on 'Platelet transfusion'.)
Patients with prior balloon angioplasty — Less than 5 percent of all PCIs are performed using balloon angioplasty without stenting. In these patients, 14 days of DAPT is generally recommended. (See "Antithrombotic therapy for elective percutaneous coronary intervention: General use", section on 'Patients undergoing balloon angioplasty'.)
There are no high-quality studies that address the optimal approach to these patients who need noncardiac surgery. If possible, we and others suggest waiting at least 14 days before performing surgery . For patients who must undergo surgery in a shorter time frame, and in particular when antiplatelet therapy must be stopped (eg, neurosurgical procedures), we suggest deferring surgery for at least 48 hours after balloon angioplasty if possible.
RECOMMENDATIONS OF OTHERS — Our recommendations for patients with coronary stents undergoing noncardiac surgery are generally consistent with those from the American College of Chest Physicians, American College of Cardiology, and the European Society of Cardiology/European Association for Cardio-Thoracic Surgery [31-35].
POTENTIAL ALTERNATIVES TO DUAL ANTIPLATELET THERAPY — The concept of bridging a gap in platelet P2Y12 receptor blocker therapy using an intravenous glycoprotein IIb/IIIa inhibitor such as tirofiban or eptifibatide is under investigation [36,37]. Some academic medical centers have used such a bridging strategy in patients at high risk for stent thrombosis . However, such a strategy is likely to be associated with a higher risk of bleeding.
Ticagrelor has a shorter clinical half-life than clopidogrel or prasugrel, and can be stopped 48 to 72 hours before surgery. Its role as a substitute for these other P2Y12 receptor blockers in this setting has not been evaluated.
Parenteral anticoagulants such as heparin do not decrease the risk of stent thrombosis and should not be used as a substitute to antiplatelet therapy.
SUMMARY AND RECOMMENDATIONS
●Noncardiac surgery is often required in patients taking dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with stenting. Cessation of DAPT prior to the recommended duration of its use, as well as the prothrombotic and proinflammatory state associated with surgery, contribute to an increased risk of adverse cardiovascular events such as stent thrombosis, myocardial infarction, or death. On the other hand, for some patients such as those undergoing neurosurgical procedures, the risk of bleeding attributable to DAT may be greater than the risk of an adverse cardiovascular event off such therapy. (See 'Introduction' above and 'Complications' above.)
●The following are our recommendations for patients taking DAPT after PCI with stenting for whom elective noncardiac surgery is needed. The rationale for the durations presented below is given above (see 'Elective noncardiac surgery in stented patients' above):
•We recommend deferring noncardiac surgery for at least 12 months, as opposed to operating sooner, irrespective of stent type (Grade 1C).
•In patients who cannot wait at least 12 months for noncardiac surgery, we recommend that an attempt be made to defer surgery for at least 30 days after bare metal stent placement and at least six months after drug-eluting stent placement (Grade 1B).
•For most patients undergoing noncardiac surgery who are taking DAPT after PCI with stenting because they have not reached the recommended duration of such therapy, we suggest continuing DAPT, as opposed to stopping it prior to surgery (Grade 2C).
In patients for whom the risk of bleeding is likely to exceed the risk of a perioperative event due to the premature cessation of DAPT, we attempt to continue aspirin alone. In patients for whom a bleeding complication could be catastrophic, such as patients undergoing neurosurgical, prostate, or posterior eye procedures, stopping both antiplatelet agents might be reasonable. (See 'Timing, incidence, and clinical predictors' above.)
●For patients taking DAPT after PCI with balloon angioplasty who are scheduled to undergo elective noncardiac surgery, we suggest waiting at least 14 days after PCI (Grade 2C). (See 'Patients with prior balloon angioplasty' above.)
●Recommendations for patients taking long-term aspirin monotherapy undergoing noncardiac surgery and for patients undergoing coronary artery bypass graft surgery on DAPT are found elsewhere. (See "Perioperative medication management", section on 'Aspirin' and "Medical therapy to prevent complications after coronary artery bypass graft surgery", section on 'Preoperative aspirin' and "Medical therapy to prevent complications after coronary artery bypass graft surgery", section on 'Platelet P2Y12 receptor blocker therapy'.)
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