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- Robert M. Califf, MD, FACC* ()
- ↵⁎Reprint requests and correspondence:
Dr. Robert M. Califf, Duke Clinical Research Institute, PO Box 17969, Durham, North Carolina 27715
The publication of two reports (1,2) in this issue of the Journalconcerning the five-year follow-up of randomized clinical trials of percutaneous coronary intervention (PCI) with stenting versus coronary artery bypass graft surgery (CABG) is a significant milestone in our understanding of the evolution of coronary disease treatment. Both of these studies represent highly commendable and badly needed efforts to clarify the data concerning a major life decision for many people with coronary artery disease. These two studies in composite show no difference in medium-term (five-year) mortality between PCI and CABG and a substantially lower need for repeat revascularization in the patients randomly assigned to surgery. The studies are discrepant with regard to nonfatal events, with a clear trend toward a lower composite event rate (death, myocardial infarction, or stroke) with surgery in the Arterial Revascularization Therapies Study (ARTS) and no such trend in the Argentine Randomized Trial of Coronary Angioplasty With Stenting vs. Coronary Artery Bypass Surgery in Patients With Multivessel Disease (ERACI II). Both studies show a highly significant difference in repeat revascularization favoring surgery and a more modest benefit of surgery with regard to angina over time. Interestingly, the ERACI II study found a higher cost per patient over time with an initial strategy of PCI.
Interpreting randomized clinical trials
On the surface, the aforementioned answers appear clear, but there are multiple issues to be considered before generalizing these findings to routine clinical practice. The sum of these issues relegates these studies to a non-definitive, albeit important, addition to our knowledge base.
Although the effort put into these trials should not be overlooked, together they include only 137 deaths, an insufficient number to detect the modest differences that have been identified as clinically meaningful. Therefore, the similarity in mortality for the two strategies cannot be declared sufficient to conclude that no difference exists, although the potential size of a mortality difference can be limited to modest magnitude by these findings. Both studies were designed to have the power to look at shorter-term composite end points and, therefore, were not intended to provide a definitive answer on mortality. Despite these limitations, more studies should consider extending follow-up beyond the time specified in the primary end point to produce incremental knowledge, as both of these studies did.
Additionally, both studies randomly assigned patients with relatively less severe forms of multivessel coronary disease. This decision is understandable because a patient had to be suitable for both procedures to be assigned; accordingly, 40% to 60% of the patients had two-vessel disease with well-preserved left ventricular function, and the median age (61 to 62 years) was young by today's standards. Therefore, these results cannot be extended to more severe forms of disease.
Finally, the high early surgical mortality in the ERACI II study remains a legitimate source of debate. The ERACI II study investigators deserve credit for honestly depicting their results. They also have used external comparisons to justify the apparently high rate of early mortality in the surgical group (13 deaths in the first month after surgery, with 5 attributed to non-cardiac causes). It appears that the surgical arm of the ERACI II study had exceedingly bad luck, and there is reason to worry somewhat about the quality of the grafts and whether follow-up outcomes beyond 30 days may have been affected.
The goals of the biomedical research enterprise should be to develop and use technology that prolongs or improves human life and to provide the people who will be affected (and their trusted physicians) with the information needed to make good choices about the use of the technology. No one can criticize the ingenuity of the interventional cardiology community in developing new technologies that benefit patients, but our ability to provide the right circumstances for the best decision-making has lagged.
It is likely that most people undergoing coronary angiography are not told the entire story when a decision is made about undergoing a percutaneous intervention. In most circumstances, the patient is referred to a cardiologist, who does an angiogram with a plan of placing a coronary stent in “the same sitting.” Cardiologists are growing weary of accusations of “self-referral,” but in fact in these settings the financial incentives are lined up in a single direction. Furthermore, once a diagnostic catheterization is completed and the wheels of revascularization are set in motion, the patient is in no position to have rational input into the decision, nor is there an appropriate setting for alternative viewpoints to be expressed by cardiac surgeons. Given the large number of cases today and the rapid growth expected due to the aging of the population, as well as the emphasis placed on rapid revascularization, it is daunting to consider more time-consuming approaches to informing patients, but we must strive to do so.
What about drug-eluting stents?
In 2003 Hoffman et al. (3) published a systematic overview of 13 randomized clinical trials comparing percutaneous transluminal coronary angioplasty and CABG, demonstrating a 1.9% survival advantage for CABG over percutaneous transluminal coronary angioplasty. However, although follow-up was available for only one to three years in the stent trials, when trials using stents instead of balloon angioplasty without stents were compared, the survival difference was not evident. One of the concerns about interpreting these studies is the possibility that drug-eluting stents have improved the situation dramatically relative to bare-metal stents. In a manner similar to the impact of bare-metal stents compared with non-stent balloon angioplasty, drug-eluting stents further reduce restenosis (4). However, they unfortunately appear to have no effect on death and nonfatal myocardial infarction relative to bare-metal stents (5,6). In fact, there is reason for concern that outside of the setting of clinical trials, the difficulty frequently encountered by patients in adhering to thienopyridine treatment regimens exposes them to a risk of abrupt thrombotic closure, even months after stent implantation (7–9).
During the time since these studies were initiated, coronary bypass surgery procedures have undergone a much less highly touted progressive improvement, as evidenced by better survival with bypass surgery compared with PCI in a recent publication from the Cleveland Clinic (10), and two additional reports currently in review from New York State (11) and Duke (Peter Smith, MD, personal communication, March 11, 2005). Nevertheless, drug-eluting stents should mitigate the major difference in the ARTS and ERACI II studies—the need for more repeat revascularization procedures after percutaneous intervention. Ongoing trials should further clarify the divergent information streams in this comparison.
Should it be stents versus surgery?
In an ideal future, cardiologists and cardiac surgeons will have a continuous learning mechanism of registries and trials that will result in more rapid improvement as technologies and procedures are introduced, evaluated, and adopted or discarded. The historical remnants of artificial, turf-oriented demarcations that deprive patients of optimal integration of practices will be eliminated. Patients and their families will have the opportunity to know the statistics, both overall and in the local environment, for therapeutic options so that the choice of procedure will be based on the needs of the patient rather than the specialty of the physician consulted. Furthermore, the hybrid procedure will likely eventually be a realistic expectation; many patients could benefit from an internal thoracic artery implant to the left anterior descending artery with stenting of other vessels (12).
Until that ideal world is reached, we should strive within our microenvironments to develop quality-measurement systems, participate in clinical research that defines quality, and adapt practice to integrate new findings as they evolve. Our patients deserve to hear the full, unbiased story as they make these life-changing decisions about coronary revascularization. For that to happen, we need more information of the type produced by the ERACI II and ARTS studies, and it will need to come at a faster rate. We also need to re-engineer the clinical enterprise so that such important decisions are made in the most informed manner possible, while maintaining consistency with the sensibilities and preferences of the patient.
Dr. Califf is Director of the Duke Clinical Research Institute, which has research contracts with coronary stent manufacturers, including Guidant, Medtronic, and Cordis Inc. The Duke Clinical Research Institute also has contracts with multiple companies that produce and sell ancillary medications used in patients undergoing bypass surgery or percutaneous intervention. Dr. Califf receives no personal compensation from any of these companies as all research contracts are made with Duke University.
↵⁎ Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
- American College of Cardiology Foundation
- ↵Serruys PW, Ong ATL, van Herwerden LA, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial. J Am Coll Cardiol 2005;46:575–81.
- Rodriguez AE, Baldi J, Fernández Pereira C, et al. Five-year follow-up of the Argentina randomized study coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II). J Am Coll Cardiol 2005;46:582–8.
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