Chapter 135 Perioperative Management of the Patient With Coronary Stents
Coronary stent insertion has become a mainstay of therapy for patients with obstructive coronary artery disease (CAD).20 The advent of the drug-eluting stent (DES) has improved long-term outcomes after coronary stent therapy by reducing the rate of restenosis (renarrowing) after stent insertion. However, the antiproliferative mechanism whereby drug-eluting stents reduce restenosis also delays reendothelialization of the stented segment. As such, extended periods of dual antiplatelet therapy with both aspirin and a thienopyridine (clopidogrel [Plavix], ticlopidine, prasugrel) are required to prevent stent thrombosis and subsequent myocardial infarction.3 Premature cessation of dual antiplatelet therapy for elective surgical procedures can thus result in subsequent stent thrombosis and myocardial infarction with catastrophic consequences, including a significant mortality rate.2,15,21 Current guidelines for patients treated with a DES recommend at least 12 months of dual antiplatelet therapy prior to elective surgery.13 Maintenance therapy with aspirin alone is advised during elective surgery performed more than 12 months after DES stent implantation to prevent late stent thrombosis. Cessation of all antiplatelet therapy can result in stent thrombosis even years after coronary stent implantation and should be reserved only for those procedures that have a prohibitively high risk of perioperative bleeding on antiplatelet therapy. Perioperative assessment of CAD patients with prior stent therapy is limited to clinical assessment prior to elective surgery, unless there are concomitant cardiovascular disease states that identify a high-risk clinical subset (American College of Cardiology [ACC]/American Heart Association [AHA] perioperative clinical guidelines).7 The management of CAD patients who have undergone coronary stent implantation requires careful attention to the timing of elective surgery relative to antiplatelet therapy to minimize the risk of periprocedural stent thrombosis and myocardial infarction.
Over 2 million patients are treated with coronary stents in the United States annually.20 Catheter-based techniques for the treatment of obstructive CAD have evolved from balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]6,16,21) to DES coronary stent therapy. The mechanism of balloon angioplasty to treat an obstructive coronary artery stenosis includes compression and fracture of the rigid components of the atherosclerotic plaque, with stretching of the elastic elements of the vessel wall. There is barotrauma to the arterial wall, including endothelial denudation and creation of dissection planes into the media and adventitia. The arterial response to balloon injury includes endothelial regeneration, neointimal proliferation as the result of migration of vascular smooth muscle cells from the media toward the luminal surface, and elastic recoil of the elastic fibers in the media and adventitial layers of the coronary artery.4,5
There are two major limitations of PTCA. Dissection of the vessel wall, which typically occurs after balloon inflation, can result in acute vessel closure and myocardial infarction, often requiring emergency coronary bypass surgery.9 Coronary stent therapy compensates for the acute complications of PTCA by sealing off dissection planes, thus leading to improved acute procedural outcomes.
Renarrowing late after PTCA, known as restenosis, occurs in 15% to 40% of patients within 6 months after successful PTCA, and is caused by neointimal hyperplasia and elastic recoil.11 Most restenosis after PTCA is caused by elastic recoil of the arterial wall after balloon stretching at the PTCA site. Stents provide a rigid endoskeleton in the treated coronary segment. By eliminating elastic recoil, coronary stents significantly reduce the rate of late restenosis after percutaneous coronary revascularization.6 Randomized clinical trials with coronary stents composed of a stainless steel strut (bare metal stent [BMS]) have demonstrated improved acute procedural success and reduced restenosis. Reendothelialization after BMS placement is thought to occur within 3 to 4 weeks after stent implantation.
The major component of restenosis after successful BMS therapy is smooth muscle cell proliferation in the stented segment. This neointimal hyperplasia is a response to the balloon injury that necessarily occurs during stent implantation. Late in-stent restenosis continued to be a significant clinical problem after BMS therapy. The advent of a DES coated with either the antiproliferative agent sirolimus (and subsequent generations) or paclitaxel, a microtubule inhibitor, has greatly reduced the rate of in-stent restenosis as compared with use of a BMS by as much as 50% to 70%.16,21,22 A DES has a polymer coating that permits the release of an antiproliferative drug into the local arterial wall over time to inhibit the migration of vascular smooth muscle cells into the area of arterial injury; this consequently limits the magnitude of subsequent smooth muscle cell proliferation. There is less cellular proliferation in response to balloon injury, which corresponds to a lower rate of clinical restenosis.10,17
However, the antiproliferative mechanism whereby drug-eluting stents reduce restenosis also delays reendothelialization of the stented segment. An intact and functional endothelial layer in the coronary artery is necessary for endogenous antithrombotic function, which prevents thrombosis of a stented coronary segment. As such, extended periods of dual antiplatelet therapy with both aspirin and a thienopyridine are required to prevent stent thrombosis as the treated arterial segment heals over time. Synergistic platelet inhibition with aspirin and thienopyridine therapy provides an optimal pharmacologic strategy to prevent stent thrombosis, which is a platelet-mediated event.18,19 Platelet aggregation and subsequent thrombus formation on exposed (and unendothelialized) stent struts may result in stent thrombosis and occlusion of the treated coronary artery, with acute myocardial infarction and death.23
The management of patients who have undergone coronary stent implantation requires careful attention to the timing of elective surgery relative to periprocedural antiplatelet therapy. Premature cessation of dual antiplatelet therapy for elective surgical procedures can result in subsequent stent thrombosis and myocardial infarction with catastrophic consequences, including a significant mortality rate (5% to 12.5% stent thrombosis–myocardial infarction, with 50% to 70% mortality in these patients1). The time frames for cessation of thienopyridine therapy are different for BMS and DES patients. Current guidelines recommend maintenance of at least 4 (and preferably 8) weeks of dual antiplatelet therapy with aspirin and a thienopyridine (clopidogrel, ticlopidine, or prasugrel) after BMS implantation and at least 12 months of dual antiplatelet therapy after DES implantation. It is recommended that patients more than 12 months out from DES therapy be maintained on aspirin, 81 mg daily, throughout elective surgery.13 Cessation of all antiplatelet therapy in BMS and DES patients should be reserved only for those procedures in which the risk of major hemorrhage outweighs the risk of periprocedural myocardial infarction. In fact, cessation of all antiplatelet therapy can result in a rebound effect, with increased platelet reactivity, which may predispose a patient to stent thrombosis.14
The incidence of stent thrombosis in a retrospective meta-analysis of BMS- and DES-treated patients between 1 and 4 years after stent insertion who were maintained on antiplatelet therapy was 1.4% to 1.7% in the BMS group and 1.2% to 1.5% in the DES cohort. Stent thrombosis in these patients was associated with more than an 80% incidence of acute myocardial infarction and a mortality rate in excess of 30%.15 Thus, there are catastrophic consequences to coronary stent thrombosis, which can occur even when appropriate antiplatelet therapy is continued. Early cessation of clopidogrel has been associated with a significant increase in stent thrombosis in patients treated with DES.12
Little data exist regarding outcomes in patients with BMS or DES for whom all antiplatelet therapy was temporarily stopped for noncardiac surgery. Wilson and colleagues25 have performed a retrospective analysis of 207 patients from the Mayo Clinic database who underwent noncardiac surgery 1 to 60 days after BMS therapy. Aspirin and thienopyridine (ticlopidine or clopidogrel) therapy were held prior to surgical procedures that required a significant incision and who were considered to have significant risk for major bleeding, such as genitourinary or head and neck surgery. Eight patients suffered stent thrombosis complicated by acute myocardial infarction (4.0%). All eight underwent surgery within 6 weeks after stent placement. There were six deaths in this group (3%). There was no incidence of stent thrombosis in those patients undergoing surgery for whom antiplatelet therapy was withheld 7 to 9 weeks after BMS implantation. These data appear to correlate well with the concept that reendothelialization of the stented segment occurs within 8 weeks after BMS placement.24 It was concluded in this retrospective study that waiting at least 6 weeks after BMS placement before cessation of antiplatelet therapy for noncardiac surgery is associated with a very low incidence of stent thrombosis, myocardial infarction, and death. Similar findings were observed in a smaller study of patients who underwent noncardiac surgery early after BMS implantation. A 50% incidence of major complications (e.g., perioperative myocardial infarction, death) occurred when surgery was performed within the first 6 weeks after stent implantation; no events were observed in those patients for whom procedures were delayed 6 weeks.19 These data further support the strategy of BMS (rather than DES) implantation in a patient who requires coronary stent therapy prior to a planned surgical procedure, albeit with a higher risk of late restenosis.
Outcomes of patients with DES who underwent noncardiac surgery are again limited to small observational studies. A review of these data was recently published by Abualsaud and Eisenberg.1 Cessation of dual antiplatelet therapy was identified as the most important predictor of stent thrombosis. The incidence of the composite end point of a major adverse cardiac event (MACE; e.g., stent thrombosis, myocardial infarction, death) ranged from 2.2% to 12.5%. Most events occurred in those patients for whom all antiplatelet therapy was discontinued in advance of surgery, and for whom surgery was performed early (<12 months) after DES implantation.
There are no data at present to suggest that short-acting intravenous antiplatelet or antithrombin inhibitors can function as bridging therapy for a coronary stent patient who requires noncardiac surgery. In fact, there is a risk of enhanced platelet reactivity caused by a rebound phenomenon as antiplatelet therapy is withheld. Catecholamine release as the result of surgery can also increase platelet reactivity and aggregation leading to thrombosis.14