VIEWPOINT
Are Drug-Eluting Stents the Preferred Treatment for Multivessel Coronary Artery Disease?
Lloyd W. Klein, MD, FACC*
Rush Medical College, Chicago, Illinois, and Clinical Cardiology Associates, Gottlieb Memorial Hospital, Melrose Park, Illinois
Manuscript received June 27, 2005;
revised manuscript received August 1, 2005,
accepted August 2, 2005.
* Reprint requests and correspondence: Dr. Lloyd W. Klein, Gottlieb Memorial Hospital, Professional Office Building Suite #314, 675 West North Avenue, Melrose Park, Illinois 60160. (Email: lloydklein{at}comcast.net).
 |
Abstract
|
|---|
Drug-eluting stents (DES) constitute a major breakthrough in restenosis prevention after initial percutaneous coronary intervention (PCI). Target lesion and vessel revascularization rates of <10% at six months follow-up represent a significant medical advance. Many cardiologists consider it reasonable to assume that PCI using DES ought to be considered equivalent, if not superior, to bypass surgery. The argument made is that in previous randomized clinical trials comparing PCI to coronary artery bypass grafting, restenosis was the determining factor favoring surgery, an event that clinical experience suggests is no longer as frequent. In the absence of a definitive clinical trial to support this view, how should the prudent, cutting edge cardiologist evaluate the data and manage their patients?
|
Abbreviations and Acronyms
| | ARTS = Arterial Revascularization Therapies Study | | BMS = bare-metal stent | | CABG = coronary artery bypass grafting | | CAD = coronary artery disease | | DES = drug-eluting stents | | ERACI = Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty versus Coronary Artery Bypass Surgery in Multivessel Disease | | PCI = percutaneous coronary intervention |
|
Insanity: doing the same thing over and over again and expecting different results.
Albert Einstein (1)
Percutaneous coronary intervention (PCI) surpasses coronary artery bypass grafting (CABG) as the most frequent revascularization modality for obstructive coronary disease (CAD). The application of PCI to multivessel CAD, however, has been limited by restenosis, which developed in 30% to 40% with balloon angioplasty and 20% to 25% in the bare-metal stent (BMS) era (2). As a consequence, CABG was demonstrated to have better long-term outcomes than PCI with BMS and/or balloon angioplasty in two- and three-vessel CAD. The problem of stenosis recurrence is especially relevant in diabetics, those with diffuse CAD, and patients with chronic total occlusions, who comprise a large proportion of patients with multivessel CAD that could potentially be candidates for PCI rather than CABG.
Although restenosis rates have been steadily decreasing since the mid-1990s, the anti-proliferative drug-eluting stents (DES) constitute a major breakthrough in restenosis prevention after initial PCI. Target lesion and vessel revascularization rates of <10% at six months follow-up represent a significant medical advance. Because prior clinical trials comparing PCI techniques versus CABG showed that restenosis is the primary drawback, many interventionists consider it reasonable to assume that PCI with DES now ought to be considered equivalent, if not superior, to bypass surgery. The argument is made that, in previous randomized clinical trials comparing PCI to CABG, restenosis was the determining factor favoring surgery, an event that clinical experience suggests is no longer as frequent. In the absence of a definitive clinical trial to support this view (although such trials are being organized at this time) how should the prudent, cutting-edge cardiologist evaluate the data from the studies that are currently available?
|
The target: CABG
|
|---|
For PCI to replace CABG as preferred therapy in multivessel CAD, clinical trials must demonstrate that long-term outcomes are at least equivalent. The challenges that must be overcome include restenosis and the inability to treat chronic total occlusions and small vessels with diffuse disease, particularly in diabetics. Coronary artery bypass grafting has provided greater durability (3) and more complete revascularization than PCI in the past. In general, the more diffuse the CAD, the more compelling the choice of CABG, particularly if left ventricular function is depressed, whereas patients with less diffuse disease and focal lesions are traditionally considered good candidates for PCI (2).
Few cardiologists are satisfied with that conclusion. The desire to refer fewer patients to CABG and offer as many as possible the advantages of PCI is appealing to many. There has been an overall average increase of 17.3% in the incidence of PCI from 72.0 of 10,000 Medicare beneficiaries to 89.3 of 10,000 Medicare beneficiaries over three years earlier this decade. Simultaneously, CABG procedure incidence rates have been declining slightly (51.0 of 10,000 to 49.2 of 10,000) (4). The angiographic and clinical characteristics of those undergoing PCI have markedly changed, with far more complex cases being treated by PCI despite no discernible decrease in outcomes. Drug-eluting stents diminish restenosis to less than double digits in simpler cases, raising the possibility that perhaps it would be useful also in complex CAD cases. If so, this approach would be significantly cost effective compared to CABG, especially with the possibility of increased utilization of stenting in diabetics, smaller diameter vessels, and multivessel CAD (5,6).
|
Clinical trials
|
|---|
The fact that these trends exist despite clinical trial and registry data which show that CABG has excellent outcomes highlights the problem of translating scientific evidence to clinical practice. The underlying issue is that both randomized trials and registries have inherent shortcomings. Even well designed randomized trials may be obsolete on completion because of shifting targets due to rapid technologic progress (e.g., BMS vs. DES). Then, trial designs may not conform to decision-making in clinical practice, rendering their conclusions difficult to apply and subject to debate. Finally, when the outcomes conflict with preconceived notions, the tendency is to question their relevance on grounds of design or analytic flaws.
The initial clinical trials testing the efficacy of DES versus BMS (7–9) evaluated their utility primarily in simple, short, single lesions. While this trial design was successful in demonstrating the benefit of DES compared to BMS, it also raised questions about their true efficacy in the kinds of lesions that are treated in every day clinical practice, because only a small percentage of cases involve the type A, straightforward lesions treated in these trials. For example, diabetics were included but only as an underpowered subset. Bifurcation lesions were mainly excluded; the presence of thrombus was an exclusion criterion, as were long lesions. Consequently, clinical studies evaluating the incidence of late stent thrombosis came well after hundreds of thousands of patients had received the device and suggest that bifurcations and overlapping multiple stents may be problematic.
Randomized trials are underway to evaluate whether DES provide outcomes similar to CABG in multivessel CAD when technically feasible. It is important to note that interventional cardiology has traveled down this road before, in fact, twice. Randomized trials of balloon angioplasty versus CABG in multivessel CAD were undertaken in the early and mid-1990s; the results were disappointing but demonstrated how much progress had been made and what needed to be done in the future (10–14). Although survival was roughly similar regardless of initial revascularization procedure, more angina, less functional improvement, and the need for repeat procedures were more frequent in the PCI patients. One important exception was the diabetic patient, in whom survival was reduced if PCI was performed as the initial revascularization procedure (10–12). Later, the introduction of BMS appeared to alter the restenosis rate sufficiently to try again in the late 1990s. However, the interventionists’ optimism again was premature; despite less cost and equal protection with respect to death and myocardial infarction, the higher repeat revascularization rate and less relief of angina persisted (15–17). A recently published registry supports this conclusion, although the data have been incorrectly interpreted as applicable to the current generation of stenting (18).
An excellent example of a registry that appropriately reflects case selection in clinical practice is the Arterial Revascularization Therapies Study (ARTS)-II trial, which was presented at the American College of Cardiology convention in March 2005 (19). A total of 607 patients treated with sirolimus stents were enrolled in a non-randomized registry. The outcomes of these patients were compared to the CABG (n = 602) and BMS arms (n = 600) of ARTS-I (16). In the ARTS-II trial, patients were more frequently diabetic (26.2% vs. 18.2%), had more three-vessel CAD (54% vs. 28%), and had more C-type lesions (13.9% vs. 7.5%) compared to the ARTS-I trial. There was no difference in the major cardiovascular events at one year between the ARTS-II DES trial registry patients and CABG randomized patients in the ARTS-I trial (10.4% vs. 11.6%), and there was no difference in any other outcome. This study is widely interpreted as suggesting that current generation DES have similar outcomes as CABG; however, its non-randomized nature and comparison with a non-concurrent CABG group leaves the question open.
On the other hand, the results of Comparison of a Polymer-Based Paclitaxel-Eluting Stent with a Bare-metal stent in Patients with Complex Coronary Artery Disease (TAXUS-V) could be interpreted more equivocally (20). The primary end point, target vessel revascularization for ischemia at nine months, was diminished in the paclitaxel stent group compared to BMS (12.1% vs. 17.3%, p = 0.018). However, there was a higher rate of major adverse cardiac events in the subgroup of 379 patients who received multiple stents (8.3% vs. 3.3%, p = 0.047), and overlapping stents were considered a risk factor for worse outcomes. An increased likelihood of adverse events was associated with side branch narrowing and closure (p = 0.03) and decreased Thrombolysis In Myocardial Infarction flow grade (p = 0.02) with the DES. How these factors might manifest in a clinical trial versus CABG is speculative at this time.
The problems of subacute and late stent thrombosis, however, could clearly impact such a comparison. A further call for caution is sounded in this issue of the Journal. Rodriguez et al. (21) from the Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty versus Coronary Artery Bypass Surgery in Multivessel Disease (ERACI) III trial report an incidence of stent thrombosis of 3.1% in the 18 months after stent implantation in 225 patients with multivessel CAD. The authors report three cases of stent thrombosis in the first month, three others in the first year, and one additional case two and a half years after stent placement. In the patients who experienced this complication, associated with discontinuation of anti-platelet therapy, six had an ST-segment elevation myocardial infarction, and three died. This report follows a recent German and Italian study (22) that also highlighted the problem of stent thrombosis. A total of 2,229 consecutive "real-world" patients underwent successful DES implantation at three European hospitals over a 21-month period. At nine-month follow-up, 29 patients (1.3%) had suffered stent thrombosis, including 14 patients with subacute thrombosis (0.6%) and 15 patients with late thrombosis (0.7%). Among these 29 patients, 13 died. There was no difference in incidence between sirolimus or paclitaxel stents.
The critical role of how efficacious DES are in the diabetic subgroup is underappreciated (23). The fact is that if a target vessel revascularization rate of >10% to 15% exists in the diabetic population, it would be statistically impossible to prove a benefit versus CABG. However, dedicated trials and subgroup analyses of larger studies, do show revascularization rates approaching this magnitude. In ISAR-Diabetes, for example, the target lesion revascularization rate at 9 months was 12.2% with Taxus and 6.4% with Cypher.
|
The bias of cardiologists
|
|---|
There are several reasons why cardiologists are seduced repetitively into thinking that things have changed. In large part, we are victims of enthusiasm about our craft. We know the advantages of PCI to patients and the health care system. We want to be persuaded by the outstanding results of clinical trials and registries that the corner has been turned. Although the presentations of the studies are scientifically valid, and are delivered by outstanding investigators and interventionists who strive to accurately portray the limitations of each study, their sincere and honorable passion for finding the new device or approach that will solve this problem are difficult to ignore.
On the other hand, although skepticism is healthy, it also may be blinding! To recognize when a real advance has been achieved, it is crucial that outstanding investigators publish their non-randomized observations periodically so that we can accurately gauge the current status of the field.
It is also essential to recognize that cost factors into this issue more than most physicians acknowledge. The fact is that cost savings is an important component of the attractiveness of a percutaneous approach to multivessel CAD. The utilization of DES was expected to result in conversion of some CABG procedures to PCI, shifting some resource-intensive patients into less expensive therapy and expand the percutaneous treatment option. An initial formal analysis by Cohen et al. (6) suggested that DES are cost-effective in patients estimated to have a clinical restenosis rate greater than 12% to 14%. These calculations were strongly dependent on the price of DES, which has decreased substantially since the publication of these evaluations, and reimbursement, which also has improved. Rao et al. (23) recently reported on the difficulties that were experienced in increasing the utilization of these devices after their introduction. Many of the original economic assumptions made by third party payers and commercial interests were faulty and took time to correct (5).
Replacing CABG as the preferred therapy for two- and three-vessel CAD would not only save patients’ pain and loss of productivity, but also money. Because the reimbursement rate for CABG and PCI with DES differ by  $15,000, conversion of even a modest proportion of CABG procedures to PCI would have a favorable impact on health expenditures (4). While the expected rate of such conversion was difficult to project, at least one retrospective study suggested that a 21% conversion rate might be expected within one to two years after the introduction of DES (25). Assuming these estimates are accurate, the potential economic benefit to society is many hundreds of millions of dollars yearly.
Consequently, Medicare agreed before DES were released to pay an additional base amount of approximately $1,800 over and above the BMS procedure reimbursement rate. This level of reimbursement was determined on the basis of calculating that profit (for Medicare) would be attained when the average number of DES per procedure reached 1.8 and the conversion from BMS and CABG were over 80% and 15%, respectively (4); Medicare determined that health care expenditures would decrease if DES were widely adopted and converted 15% of CABG to multivessel PCI. However, they failed to recognize that under this reimbursement scheme, PCIs involving >2 DES would actually lose money for most hospitals. Hence, the calculated reimbursement level did not reward conversion to DES and actually served as an impediment to its utilization (5,6,24). The improved price of these products since their introduction resulting from competitive forces has favorably altered the economic equation.
|
Current state-of-the-art
|
|---|
Several recent studies suggest, however, that although cardiologists want to believe that DES ought to be the preferred therapy, there may be serious concerns, aside from restenosis, which have not been sufficiently considered in the past. Certainly the issue of vulnerable plaque progression has received substantial emphasis over the past few years. The antiquated notion of predicting the likelihood of a coronary stenosis demonstrated at coronary angiography to progress to cause a myocardial infarction is no longer tenable. Yet despite the fact that rapid progression of a vulnerable stenosis due to plaque rupture and acute thrombosis is an accepted principle, clinically we still practice as if the "high grade" stenosis requires urgent attention while less significant luminal obstructions can be treated less aggressively. In part, this discrepancy is the product of a lack of technology that allows us to identify the vulnerable plaque before it ruptures. Also, we do not yet completely understand how commonly plaque ruptures, in what time frame, or with what consequences. Finally, we are not sufficiently knowledgeable as to the risk:benefit ratio of current medical and procedural therapies to know what direction to take, even if we could reliably identify such lesions.
The communications from the ERACI III trial (21) and the European registry (22) discussed above suggesting that stent thrombosis may occur at a higher rate than usually appreciated should be of concern to those advocating a head-to-head comparison at this time. If the actual rate of stent thrombosis causing myocardial infarction in the first year is on the order of 1% to 3% as reported in these trials, it is difficult to conceive of how the hard numbers in any clinical comparison could favor PCI.
Perhaps the most disquieting new observation is that the increased need for repeat interventional procedures, either at the same site or within the same vessel(s), is not entirely related to restenosis at the site of the previous obstruction and the stent placed as treatment. The recent National Heart, Lung, and Blood Institute Dynamic Data registry (26) presented an elaborate analysis strongly suggesting that, in the current stenting era, progression of disease may be the imperative concern. The authors evaluated the rate of progression of non-target lesions over one year after PCI. The authors reported that 6% of lesions thought not to be significant enough to be addressed by PCI had progressed over that time frame to become clinically relevant. Importantly, the data appear to suggest that the least favorable outcomes with PCI are associated with extensive severe CAD. Hence, in large measure, it is the patient with multivessel CAD at most hazard of rapid, early progression (27). Both PCI and CABG are effective therapies in the routine case, but those patients with diffuse, extensive disease and those most difficult to treat with PCI in the past—the elderly, the diabetic, the chronic renal patient—are the subset of patients with whom the future of this controversy rests. That is not a prospect thoughtful interventionists ought to relish (23).
To the extent to which these considerations are applicable to everyday clinical practice, it is possible that multiple stents of any design may have an inherent limitation when applied in complex CAD patients. Perhaps CABG succeeds precisely because of its imprecision: stents treat only the focal area of most significant occlusion while CABG may bypass the vulnerable plaques that could potentially develop into culprit lesions over time. Statin agents and other pharmacologic therapies that passivate vulnerable plaque and diminish inflammation may be just as important long-term as stents are short-term. As adjuncts of PCI or as a stand-alone treatment strategy, the power of medical therapy should not be ignored.
These observations run counter to the prevailing attitudes about the potential of DES, and accurate interpretation of clinical trial data will be the subject of much discussion and debate. Although one can hope that head-to-head trials this time will lead to a different result than in the past (23), it is vital in the interim to be cognizant of available information that suggests that the result of such trials is not a foregone conclusion. The disconcerting possibility is that the fundamental challenge ahead may lie with the patient’s disease, not the physician’s cure.
|
Addendum
|
|---|
Since this paper was submitted, Ortolani et al. (28) reported a randomized trial demonstrating that diabetics undergoing DES for focal lesions in small vessels (mean, 2.1 mm diameter) had an angiographic restenosis rate of 25%. Although this was significantly better than with BMS (63%, p < 0.002), nevertheless, the clinical MACE rate at eight months was 14%. At the American Heart Association meeting in November, Macaya et al. (29) presented the results in the diabetes subset of the ARTS II trial. At one year, there was a revascularization rate of 12.6% in the DES-treated patients versus 4.2% in the CABG patients. These studies further suggest that the diabetic patient may continue to represent a serious challenge to catheter-based interventions.
|
References
|
|---|
1. BrainyQuote. Available at: http://www.brainyquote.com/quotes/quotes/a/alberteins133991.html. Accessed November 7, 2005..2. Smith SC, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention J Am Coll Cardiol 2001;372239i–lxvi. 3. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events N Engl J Med 1986;314:1-6.[Abstract] 4. Hodgson JM, Klein LW, Bottner R, et al. SCAI Drug-eluting Stent Task Force. Final report and recommendations of the working committees on cost effectiveness/economics, medical-legal issues and access to care Catheter Cardiovasc Interv 2004;62:1-17.[CrossRef][Web of Science][Medline] 5. Klein LW, Hodgson JM. Drug-eluting stentscase study in the acceptance of a new medical technology. Catheter Cardiovasc Interv 2005;64:528-530.[CrossRef][Medline] 6. Cohen DJ, Bakhai A, Shi C, et al. Cost-effectiveness of sirolimus drug-eluting stents for the treatment of complex coronary stenosesresults from the randomized SIRIUS trial. (abstr) J Am Coll Cardiol 2003;41(Suppl A):32A. 7. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization N Engl J Med 2002;346:1773-1780.[Abstract/Free Full Text] 8. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery N Engl J Med 2003;349:1315-1323.[Abstract/Free Full Text] 9. Grube E, Silber S, Hauptmann KE, et al. TAXUS Isix- and twelve-month results from a randomized, double-blind trial on a slow-release paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003;107:38-42.[Abstract/Free Full Text] 10. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease N Engl J Med 1996;335:217-225.[Abstract/Free Full Text] 11. RITA Trial Participants Coronary angioplasty versus coronary artery bypass surgerythe Randomized Intervention Treatment of Angina (RITA) trial. Lancet 1993;341:573-580.[CrossRef][Web of Science][Medline] 12. King III SB, Lembo NJ, Weintraub WS, et al. A randomized trial comparing coronary angioplasty with coronary bypass surgeryEmory Angioplasty versus Surgery Trial (EAST). N Engl J Med 1994;331:1044-1050.[Abstract/Free Full Text] 13. Rodriguez A, Mele E, Peyregne E, et al. Three-year follow-up of the Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease (ERACI) J Am Coll Cardiol 1996;27:1178-1184.[Abstract] 14. CABRI trial participants First-year results of CABRI (Coronary Angioplasty versus Bypass Revascularisation Investigation) Lancet 1995;346:1179-1184.[CrossRef][Web of Science][Medline] 15. The SOS Investigators Coronary artery bypass surgery vs. percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial)a randomized controlled trial. Lancet 2002;360:965-970.[CrossRef][Web of Science][Medline] 16. Serruys PW, Unger F, Sousa LF, et al. Comparison of coronary artery bypass surgery and stenting for the treatment of multivessel disease. Arterial Revascularization Therapies Study (ARTS) N Engl J Med 2001;344:1117-1124.[Abstract/Free Full Text] 17. Rodriguez A, Bernardi V, Navia J, et al. Argentine randomized study: coronary angioplasty with stenting vs. coronary bypass surgery in patients with multiple vessel disease (ERACI II) J Am Coll Cardiol 2001;37:51-58.[Abstract/Free Full Text] 18. Hannan EL, Racz MJ, Walford G, et al. Long-term outcomes of coronary artery bypass grafting versus stent implantation N Engl J Med 2005;352:2174-2183.[Abstract/Free Full Text] 19. Serruys PW. ARTS-II (Arterial Revascularization Therapies Part II) Study. 2005Presented at: American College of Cardiology Annual Meeting; Orlando, FL: March 17. 20. Stone G, Ellis SG, Cannon L, et al. Comparison of a polymer-based paclitaxel-eluting stent with a bare-metal stent in patients with complex coronary artery disease (TAXUS V) JAMA 2005;294:1215-1223.[Abstract/Free Full Text] 21. Rodriguez AE, Mieres J, Fernandez-Pereira C, et al. Coronary stent thrombosis in current drug-eluting stent erainsights from ERACI III trial. J Am Coll Cardiol 2006;47:205-207.[Free Full Text] 22. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents JAMA 2005;293:2126-2130.[Abstract/Free Full Text] 23. Rao SV, Shaw RE, Brindis RG, Klein LW, Weintraub WS. Predictors of drug-eluting stent use in clinical practicedata from the American College of Cardiology-National Cardiovascular Data registry. Circulation 2004;110:III688. 24. Califf RM. Stenting or surgeryan opportunity to do it right. J Am Coll Cardiol 2005;46:589-591.[Free Full Text] 25. Ferreira AC, Peter AA, Salerno TA, Balooki H, Marchena E. Clinical impact of drug-eluting stents in changing referral practices for coronary surgical revascularization in a tertiary care center Am Thorac Surg 2003;75:485-489.[Abstract/Free Full Text] 26. Greenberg D, Bakhai A, Neil N, et al. Modeling the impact of patient and lesion characteristics on the cost-effectiveness of drug-eluting stents(abstr) J Am Coll Cardiol 2003;41(Suppl A):538A. 27. Glaser R, Selzer F, Faxon DP, et al. Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention Circulation 2005;111:143-149.[Abstract/Free Full Text] 28. Ortolani P, Ardissino D, Cavallini C, et al. SES-SMART Investigators Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (A SES-SMART Substudy) Am J Cardiol 2005;96:1393-1398.[CrossRef][Web of Science][Medline] 29. Macaya C, Garcia H, Serruys P, et al. Sirolimus-eluting stents versus surgery and bare metal stenting in the treatment of diabetic patients with multivessel disease—a comparison between ARTS I and ARTS II Circulation 2005;112:II655(abstr).
This article has been cited by other articles:
|
|
|
|
 
J. H. Yang, H.-C. Gwon, S. J. Cho, J. Y. Hahn, J.-H. Choi, S. H. Choi, Y. T. Lee, S. H. Lee, K. P. Hong, and J. E. Park
Comparison of Coronary Artery Bypass Grafting With Drug-Eluting Stent Implantation for the Treatment of Multivessel Coronary Artery Disease
Ann. Thorac. Surg.,
January 1, 2008;
85(1):
65 - 70.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H Wong, S. Wan, and M. J Underwood
Myocardial Revascularization: Surgery or Stenting?
Asian Cardiovasc Thorac Ann,
June 1, 2007;
15(3):
264 - 269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. P. Martens, M. Argenziano, and M. C. Oz
New Technology for Surgical Coronary Revascularization
Circulation,
August 8, 2006;
114(6):
606 - 614.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Guyton
Coronary Artery Bypass is Superior to Drug-Eluting Stents in Multivessel Coronary Artery Disease
Ann. Thorac. Surg.,
June 1, 2006;
81(6):
1949 - 1957.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
The target: CABG