| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
EDITORIAL |
Singapore
When drug-eluting stents became available, there was much enthusiasm since the restenosis rate employing this application appeared to be significantly better than with bare metal stents. Questions have been raised on whether there is still a place for coronary artery bypass surgery (CABG). Since the results of stents in terms of restenosis are excellent, this euphoria led Dr Patrick Serruys to state that "If I am in a dream, please don’t wake me." It is however timely to wake up the interventional cardiologists from their trance state and ask them some questions:
QUESTION 1
Can drug-eluting stents match the results from coronary artery bypass surgery (CABG), let alone do any better than CABG?
No. 30-day mortality rates for CABG is approximately 3% despite an increase in preoperative risk factors.1 Late survival following coronary artery bypass grafting has also been excellent with the Coronary Artery Surgery Study reporting survival rates of 90% at 5 years.2
QUESTION 2
Can drug-eluting stents provide global revascularization equivalent to CABG?
No. In terms of completeness of revascularization, drug-eluting stents cannot be compared to CABG. Referring to incomplete revascularization with stents, Dr Rod Stable, principle investigator of the SOS trial states that "even before restenosis has a chance of affecting the outcome, surgery is already ahead."3
QUESTION 3
Do drug-eluting stents meet the gold standards set by the left internal mammary artery (LIMA) to left anterior descending artery (LAD) anastomosis?
No. Data from the Cleveland Clinic Foundation Registry demonstrate that of 484 internal mammary grafts studied more than 10 years after surgery, 95% were still patent.4
QUESTION 4
Can we extrapolate the results of drug-eluting stent trials to the real world practice of interventional cardiology?
No. We have to bear in mind that the major drug-eluting stent trials are basically trials on simple lesions, mostly single vessel disease with short segment stenoses, in highly selected subsets of patients. The exclusion criteria of the SIRIUS trial included multi-vessel intervention, total occlusion, ostial lesion, calcified lesion, left main coronary artery stenosis, recent myocardial infarction, bifurcating lesion, and ejection fraction of less than 25%.5 A very basic tenet of biostatistics is "the enrolled patient must be similar to the general population base to permit any generalization of the results of the trials". However the trial results of a highly selected group of patients has been extended to the real world practice of interventional cardiology. (off-label use of drug-eluting stents) to include long lesions, small vessels, chronic total occlusion, multiple stents in multiple vessels, instent stenosis, vein graft stenosis and left main coronary artery stenting. All these have been done without clear evidence that it is likely to reproduce the results of the drug-eluting stents trials.
QUESTION 5
Can the results of the trials be reproduced by less competent cardiologists?
The outcome with a drug-eluting stent is still operator dependent.3 These stents still need good interventional cardiologists for good results. Outcomes are likely to be adversely affected by less competent hands.
QUESTION 6
Do drug-eluting stents prolong life span or reduce the occurrence of myocardial infraction?
No. In trials like TAXUS IV, the incidence of cardiac death and acute myocardial infarction was almost identical between drug-eluting stents and bare metal stents.4 Conventional stents had been previously shown not to prolong life or reduce the myocardial infarction rate, compared to medical therapy alone. Drug-eluting stents will not do any better in this respect either.
QUESTION 7
Are there situations that require surgery in addition to coronary artery bypass grafting?
There are many situations which require procedures like mitral valve repair, mitral valve replacement, aortic valve surgery, ventricular volume reconfiguration and maze procedures amongst others, in addition to CABG. These are situations where drug-eluting stents have no place.
QUESTION 8
Are there any concerns about the long-term outcomes of drug-eluting stents?
It is important to realize that revascularization procedures are dramas that occur over time. Time is required for adverse outcomes to be manifested. There are many unanswered questions concerning drug-eluting stents:
There is no good long-term human study on all these questions although some disturbing discoveries were noted in animal trials. Despite all these concerns, drug-eluting stents have seen widespread use without first addressing these long-term concerns.
Dr Paul Teirstein has stated that a serious rate of complication of 0.5% could affect more than 10,000 lives each year.7 Renu Virmani from Pathology Washington DC stated in 2002: "Mother Nature would not let you get away with using drug eluting stents without any aftermath. Results will become more fiercely evident after second year of intervention". In animal and human studies using scanning electromicroscopy, the endothelial linings were shown to be denuded and agitated. There was intimal inflammation, fibrin degradation, medial necrosis and plague hemorrhage following the use of drug-eluting stents.
Studying paclitaxel, Sonoda S and colleagues found that there was persistent fibrin deposition with subsequent potential to stimulate smooth muscle cell perforation.7 There is a likelihood of late intimal proliferation. Restenosis and late thrombosis are likely to be delayed but not eliminated. Intimal microphage levels were usually reduced by a factor of 10 within 80 days in bare metal stents, but were persistently high in drug-eluting stents, leading to potential late occlusion.
Synthetic polymer itself is biologically active and can cause an increase in apoptotic cells in vitro.8 The long-term effect is unknown. A potential problem is aneurysm formation. Dr Patrick Serruys stated in 2002: "Can there be an effect without side-effects? The answer is clearly no". This brings to prominence Voltaire’s well quoted phrase: "Doctors pour drugs which they know little to cure disease which they know less into human beings whom they know nothing." This is precisely the case in drug-eluting stents.
QUESTION 9
Are we creating a new iatrogenic disease?
That could potentially be difficult to treat. We may have to deal with multiple coronary aneurysms in the years to come.
QUESTION 10
Are drug-eluting stents the answer for diabetic patients?
It has been demonstrated that diabetes remains an independent predictor of poor outcome following drug-eluting stents. In patients with lesions of more than 50 mm in length and less than 2.5 mm in diameter, the restenosis rate remains at 23.7% (SIRIUS).9 The use of drug-eluting stents in insulin dependent diabetics showed no significant benefits versus bare metal stents ( p = 0.38) (SIRIUS).9
CONCLUSION
Many previous "innovations" have been touted to be the solution to problems of restenosis. These have included direct atherectomy, laser atherectomy, rotablater, brachytherapy which have all been touted previously as the grand solution to restenosis. However the hype for each has subsided over time.
All these have been shown to be ineffective. It is difficult to fool nature in the reparative process of placing foreign materials in small vessels. Only time will tell if drug-eluting stents will fall into the same category as these previous procedures. It is important to remind ourselves that we should treat the patient and not the angiographic appearance. In 1992, an excellent editorial from the Mayo Clinic proceeding states that: "Medical therapy has been forgotten options in the current mechanistic age of cardiology, in which, therapeutic results are more often measured by percentage stenosis rather than by clinical outcomes or long-term survival."10
In studies in RITA II, comparing 7-year outcomes of PCI (Percutaneous Coronary Intervention) versus medical therapy,11 it is well shown that there is no difference in terms of survival or myocardial infarction. The comment from Spencer King at the end of the RITA II trials was: "We must be honest with ourselves as well as our patients if there is no evidence to support improvement in prognosis. The patients need to hear and understand that." In advocating use of drug-eluting stents, there could be situations where patients are not fully informed about the prognosis in terms of prolonging life span, reduction of myocardial infarction or potential long-term complications.
Drug-eluting stents have resulted in a 15% reduction in the number of CABG procedures in the USA. In the study from the Cardiology Round Table, a group of 196 patients referred for elective coronary artery surgery was referred to two intervention cardiologists to consider drug-eluting stents.12 Of these, only 29% were deemed suitable to receive drug-eluting stents. The remainder, around 80%, were referred back for conventional surgery.
It can be summarized that the use of drug-eluting stents will result in a 10–20% reduction in the number of CABG procedures. Bear in mind that as the population in many countries continues to age, the incidence of coronary disease will continue to increase and the denominator in the equation will continue to rise, resulting in an increasing number of CABG.
With drug-eluting stents, the gap between intervention and CABG has narrowed but CABG will still be a major mode of therapy for coronary disease. It is likely that surgery will continue to be preferred for more complex patient subsets and the surgeons will have to continue to maintain good results in increasingly difficult patient types. Only time will tell whether drug-eluting stents will maintain the initial good results without further complications. It is important to remind ourselves that we should treat the patient and not the angiography images.
ACKNOWLEDGMENTS
Our thanks to Dr. Atasha Asmat, MD, Department of Cardiac, Thoracic & Vascular Surgery, National University Hospital, Singapore and Dr. OP Yadava, MD, Dharma Vira Heart Center, Sir Ganga Ran Hospital, New Delhi, India, for their contributions to this paper.
REFERENCES
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
S. Kant Omental Wrap for Aortic Suture Lines Asian Cardiovasc Thorac Ann, April 1, 2006; 14(2): 174 - 174. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
