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EDITORIAL

Progress Is Precarious

Diane E. Head, MD^*, and Paul Barash, MD

From the *University of Wisconsin, Madison School of Medicine and Public Health, Madison, Wisconsin; and Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut.

Address correspondence and reprint requests to Diane E. Head, MD, Department of Anesthesiology, 600 Highland Ave./CSC B6/319, Madison, WI 53792-3272. Address e-mail to dehead{at}wisc.edu.

".....progress is precarious, and the solution of one problem brings us face to face with another problem."

Dr. Martin Luther King, Jr.

The ubiquitous use of percutaneous coronary intervention (PCI) is a major advance in the management for patients with coronary artery disease. More than 1.2 million PCI procedures are performed yearly in the United States: 645,000 percutaneous balloon angioplasties (PTCA) and 620,000 coronary stents.1 Although innovation has been beneficial for patient care, history illustrates that progress often comes at a cost. Since the first report of PTCA in 1977 by Gruentzig, each generation of PCI technology has resulted in new and unanticipated problems. Bare metal coronary stents (BMS) were found to be the solution to abrupt vessel closure associated with PTCA. However, BMS are associated with in-stent coronary restenosis.2 Drug-eluting coronary stents (DES) were developed to solve the problem of restenosis, but have been linked to late stent thrombosis.

Case reports, observational studies, and meta-analyses have revealed an increase in DES thrombosis that occurs late (>30 days) or very late (>360 days) after insertion.3–5 These events are often associated with discontinuation of antiplatelet therapy and have an associated mortality rate of up to 45%.6 Patients with DES may be at especially high risk for stent thrombosis in the relatively hypercoagulable and proinflammatory perioperative period when aspirin and clopidogrel have been discontinued. A recent report suggests that withdrawal of clopidogrel results in a hyperthrombotic state, not only due to loss of drug effect but also because of a rebound increase in platelet aggregation.7 The DES saga underscores the fact that "evidence-based medicine" is not infallible, as information obtained from prospective, randomized, controlled trials is not always applicable to "real world" clinical practice. It is a sobering reminder of the importance of monitoring long-term outcomes in patients who receive new devices and drug therapies because they can have disparate outcomes when used for indications and inpatient populations other than those studied.8

According to the most recent United States Census Bureau data, the most rapid growth in the elderly population occurred in those 85 yr and older (an increase of 38% over prior years). In fact, the greeting card manufacturer, Hallmark, sold 85,000 "Happy 100th Birthday" cards in 2007! Coincident with the increase in longevity is an ever more aggressive PCI strategy adopted by cardiologists. Consequently, anesthesiologists are increasingly being called upon to manage patients with complex coronary artery disease. In this issue of Anesthesia & Analgesia, Newsome et al. presents a complete, scholarly, and extensively researched review of the current status of coronary artery stenting and its implications for perioperative care. Part I provides a thorough overview of the history and evolution of PCI, reviews stent indications, and DES pharmacology.9 Specific anticoagulation considerations are discussed, including aspirin and clopidogrel resistance. Part II of the review article details specific issues surrounding the perioperative care of patients with coronary stents who require medical interventions and surgery.10 Succinctly highlighted are current guidelines regarding antiplatelet therapy duration and timing of surgical intervention in patients with BMS and DES. An excellent resource, it examines a complex and rapidly changing topic that directly affects daily practice and provides a foundation to which further information can be added as it becomes available.

Much of the confusion and frustration in caring for patients with coronary stents results from a lack of conclusive data on which to base clinical decisions. Despite the absence of definitive answers, five issues must be considered in managing a patient with a coronary stent who presents for a surgical procedure: anticoagulation management, appropriate duration from PCI to surgical intervention, perioperative monitoring, choice of anesthetic technique, and heart catheterization laboratory access. Of these, the management of anticoagulation is of paramount importance. Dual antiplatelet therapy (aspirin and clopidogrel) is necessary until complete endothelialization of the stent occurs.11 This process is generally complete by 90 days in BMS, but is prolonged and variable in DES, and there are no readily available tests to determine when endothelialization is complete.12 Furthermore, outcomes after PCI are improved with extended aspirin and clopidogrel therapy.13 As a result, the suggested duration of antiplatelet medications is increasing, creating significant challenges for perioperative physicians regarding timing of surgical intervention after PCI. Current guidelines advocate a 1-yr delay after DES and at least a 4-6-wk delay after PTCA and BMS before elective operative intervention.14 Some authors advocate continuing dual antiplatelet therapy throughout the perioperative period, particularly in high-risk patients.15,16 Therefore, a case-by-case approach, balancing bleeding versus clotting risk is a key concept. Vigilance for myocardial ischemia is required in the perioperative period with telemetry monitoring, serial troponin measurements, and intensive care unit care as options. The decision to use continuous neuraxial anesthetic techniques should be carefully considered, as aggressive anticoagulation will be necessary in the event of stent thrombosis requiring rescue PCI.17 Because the optimum length of antiplatelet therapy is unknown for a given patient, stent thrombosis may occur even when current guidelines are followed. Therefore, it is necessary to have specific protocols that detail responsibilities of care teams before anesthetizing and operating on this high-risk group of patients. Given that stent thrombosis occurs rapidly and with disastrous consequences, one editorialist suggested that patients with DES should preferably have surgery at facilities where interventional cardiology is immediately available.18 A process should be in place for rapid patient transfer to the catheterization laboratory (such as <90 minute "door-to-balloon" time). Institutional protocols are essential to avoid delays in cardiac interventional procedures, and have been shown to reduce ischemic time and improve outcomes.19

Because of patient risk and ethical concerns, it is unlikely that a randomized, controlled trial of DES patients in the perioperative period will ever be performed. In the absence of such a study, the logical next step is the creation of a national (or international) anesthesia registry to specifically determine the incidence of perioperative risk associated with PCI, with emphasis on DES. This information cannot be gleaned from current cardiology databases. An alternative would be to gather the data in collaboration with our cardiology colleagues. In fact, a recent editorial by the president of the American College of Cardiology called for a more robust DES registry with "real world application."20 Although the risk of DES thrombosis is low (1%-3%) in a nonoperative environment, the incidence may be significantly higher in the perioperative period because of frequent withdrawal of antiplatelet therapies. Documentation of the magnitude of the problem and examination of outcomes is critical for patient safety. Although observational data do not carry the same scientific weight as randomized, controlled trials, the information obtained would allow our specialty to take a more informed, active role in perioperative decision-making.

Significant strides have been made over the last 30 yr in the treatment of coronary artery disease. The reviews by Newsome et al. present an overview of this evolution and provide insight into future developments. Although PCI is a significant advance inpatient care, history clearly demonstrates that progress is precarious, and that it has unpredictable and unintended consequences.

	Footnotes

 
Accepted for publication March 22, 2008.

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