Author + information
- Robert F. Wilson, MD⁎ ( and )
- Alan K. Berger, MD
- ↵⁎Reprint requests and correspondence:
Dr. Robert F. Wilson, Department of Medicine, University of Minnesota, MMC 508, 420 Delaware Street SE, Minneapolis, Minnesota 55455
The goal of coronary revascularization, indeed of all medical treatments, is to improve outcomes for patients, but what does “improve outcomes” mean? Usually, there are many outcomes to a treatment, relief of symptoms, reduced risk of death and disability, major complications, minor nuisances, financial impact, pain, recovery time, and so on. How do we weigh these different aspects of outcome to determine which treatment is preferred?
The study by Boudriot et al. (1) in this issue of the Journal illustrates the problem of weighing the impact of one aspect of outcome against another. The authors compared the outcomes of coronary artery bypass grafting (CABG) surgery to that of percutaneous coronary intervention (PCI) with sirolimus-eluting stents for the treatment of unprotected left main coronary artery (LMCA) stenosis. In a randomized trial involving 201 patients, they found 1-year mortality was about the same with both methods, and perioperative complications were markedly higher among patients undergoing CABG (30% vs. 4%). There was no significant difference between the treatment arms with respect to angina relief at 1 year (66.3% vs. 71.1%). That sounds like a “win” for PCI. The authors concluded, however, that PCI was inferior to CABG because repeat revascularization—the driving force in the composite primary end point—occurred more frequently among PCI patients than CABG patients (14% vs. 5.9%). What would knowledgeable patients conclude? Does an 8% reduction in repeat revascularization outweigh the increased pain and recovery time of CABG, and the higher risk of perioperative complications?
A short history of left main revascularization: a story of risk
Since its inception in 1960, CABG has been the gold standard for coronary revascularization. Compared with medical therapy alone, CABG lessens both symptoms and mortality in patients with significant stenosis of the LMCA. Medical therapy for patients with LMCA stenosis is abysmal, with a 50% survival at 7 years (2). Conversely, randomized trials consistently show CABG markedly improves survival compared with medical therapy alone. The pain, cost, and recuperation time of CABG were far outweighed by the reduction of risk and improvement of symptoms.
Because it is less painful, less invasive, and has a very short recovery time, PCI has displaced CABG as the primary method for coronary revascularization in patients who have a relatively low inherent risk of infarction and death. In these lower-risk groups (1- or 2-vessel disease, nondiabetic, preserved left ventricular function), early comparative trials of PCI and CABG consistently showed that both techniques lead to similar survival and risk of myocardial infarction (MI), but patients undergoing PCI had more repeat procedures and less angina relief over the long term (3). Patients weighed the outcomes and flocked to PCI because it was less invasive.
As PCI methods improved, its reach extended to more complex coronary disease. The risk of dissection and abrupt closure associated with balloon angioplasty limited its use to fairly limited, discrete coronary lesions. The introduction of bare-metal stents (BMS) reduced periprocedural disasters (coronary occlusion due to dissection) but only modestly reduced the risk of restenosis. This improvement in periprocedural complications led to attempts to treat LMCA lesions with BMS. Among lower-risk patients, bare-metal stenting was associated with lower in-hospital morbidity, but still exposed the individual to a higher risk of unacceptable restenosis and revascularization. Trials in high-risk patients with LMCA disease were met with an unacceptable 13.7% in-hospital mortality and a 24.2% 1-year mortality (4). At this point in PCI history, the higher risk of PCI outweighed the pain and prolonged recovery of CABG. Consequently, PCI was generally reserved for patients with an unacceptable surgical risk even though it was less invasive.
The development of drug-eluting stents (DES) and advances in bifurcation stenting during the past decade improved both immediate and long-term outcome of LMCA stenting. Six- to 12-month target vessel revascularization (TVR) rates have ranged from 2% to 19% with DES as opposed to 12% to 31% with BMS (5–7). Yet, concerns remain regarding stent thrombosis, particularly when the stent is incompletely apposed to the vessel wall, or dual antiplatelet therapy is not provided. A significant risk of catastrophic left main thrombosis with DES would not outweigh the pain and prolonged recovery of CABG.
Assessment of the current study: balancing the importance of outcomes
Every treatment has a myriad of potential complications and also a number of positive effects. To gain statistical advantage, we often combine end points. The problem is that the individual end points usually have significantly different impacts. The higher frequency of less important outcomes often overshadows the really critical outcomes, leading to false comparisons. The primary end point of the trial by Boudriot et al. (1) was driven by the increased revascularization rate in the PCI arm. Is repeat PCI important enough to be included with death and MI as a primary outcome parameter, or should each outcome be weighted?
A health economist would present the composite end point to a patient in practical terms. Recognizing the fact that a patient values survival, morbidity, and discomfort with differing levels of importance, he or she would determine the relative value of the individual end points for a patient using a “standard gamble” or “time-tradeoff” technique. In the process of assigning various weights (Table 1), the relative value of a stroke, MI, and death could be compared on the same scale. We are not sure what the correct weights are for each aspect of outcome, but considering the relative importance of each would help physicians and patients better assess the results of treatment options.
The evidence to date
Like the excellent randomized trial by Boudroit et al. (1), observational registries comparing DES with CABG among patients with LMCA disease have shown similar mortality but an excess number of periprocedural MIs following CABG. A recent meta-analysis including 1,278 patients receiving DES for LM disease (median follow-up of 10 months) found a mortality of 5.5%, TVR rate of 6.5%, and a major adverse cardiovascular event (MACE) rate of 16.5%. DES, in comparison to CABG, reduced the composite of stroke and MACE by 54% (odds ratio: 0.46 [95% confidence interval: 0.24 to 0.90]).
LeMANS (Left Main Angiographic Substudy) (n = 104), the first randomized trial comparing DES with CABG, found no significant difference between the 2 arms in regard to death, MI, or stroke (8). A subgroup analysis of patients with LMCA disease (n = 705) from the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial found no significant difference in the composite of death, MI, stroke of repeat revascularization (PCI arm 15.8% vs. CABG arm 13.7%, p = 0.44) (9). Repeat revascularization occurred more frequently among PCI patients (11.8% vs. 6.5%, p = 0.02). Among patients with coexistent disease involving the LMCA and 2 vessels or 3 vessels, however, the pendulum swung in favor of CABG.
The expansion of PCI into more complex LMCA lesion subsets will require additional randomized clinical trials, and they are underway (EXCEL [Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization] and PRE-COMBAT [Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease] trials). If the results of the present study are confirmed, then the scale may ultimately tip to PCI for selected patients with unprotected LMCA disease. All outcomes are not created equal. We need to start using the established decision-making tools to help us understand what is best for patients.
↵⁎ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. The authors have reported that they have no relationships to disclose.
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