Will Drug Eluting Stents Replace Need for CABG?

While drug eluting stenting represents a major breakthrough in interventional cardiology, there is still a significant need for coronary artery bypass graft (CABG) surgery in the treatment of patients with blocked arterial vessels, according to Bruce W. Lytle, M.D., speaking at the 39th Annual Meeting of The Society of Thoracic Surgeons, held in San Diego California on January 31-February 2, 2003.

"Although drug-coated stents are a definite improvement over bare stenting, restenosis has not been eliminated and they cannot be used in all patients," stated Dr. Lytle, Staff Surgeon, Department of Thoracic and Cardiovascular Surgery. Furthermore, we still see better long-term outcomes with the introduction of internal mammary artery (IMA) grafts and there are even better surgical approaches on the way, with less invasive surgical procedures, smaller incisions, and off-pump surgery in the near future."

The Role of CABG
In the first 35 years since the introduction of CABG, it had been demonstrated that CABG relieved angina and, more importantly, the life expectancy of these patients with coronary artery disease (CAD) had been prolonged, while other approaches had been found not to prolong life. The achilles heel of CABG was vein graft failure, with the time-limiting factor being vein graft atherosclerosis. It was found, however, that the rate of vein graft failure could be decreased somewhat by technical procedures, platelet inhibitors and statins.

Next came the discovery of the internal mammary graft approach leading to fewer cardiac events, a better survival rate, and the grafts lasting at least 20 years. In point of fact, this is the major incremental benefit of CABG surgery over percutaneous coronary intervention (PCI) grafts that stay patent are better than vessels that don't.

The Introduction of PCI
The angioplasty era can be divided into three periods, to date. These are: percutaneous transluminal coronary balloon angioplasty (PTCA); platelet inhibitors and bare coronary stents; and drug eluting stents.

The problem with balloon PTCA has always been a high restenosis rate, with long-term revascularization being considered relatively ineffective. In the BARI (Bypass Angioplasty Revascularization Investigation), study, 1829 patients with multivessel coronary artery disease who required revascularization were randomly assigned to either CABG or PTCA and followed for a mean 5.4 years. In the surgically treated patients, 95% had no angina compared to only 73% of those who underwent PTCA. Although the five-year survival was comparable in both the PTCA and CABG groups, subsequent repeated revascularization was required more often in the PTCA group, with 94% of the asymptomatic CABG patients not requiring additional revascularization procedures versus 48% of those who received PTCA. In patients with diabetes mellitus, the five-year survival was significantly worse with PTCA than with CABG.

The introduction of platelet inhibitors and bare stents resulted in a major decrease in procedure-related risks, with less restenosis and less reinterventions, albeit, clinical trial results still favored CABG. In the SOS (Stent or Surgery) study, PCI with stent placement was compared with CABG surgery in 976 randomly assigned patients with 2-vessel or 3-vessel coronary artery disease and angina pectoris. In the PCI group, stents were placed in 78% of the lesions. At one-year followup there was a significant survival difference favoring CABG, with a mortality rate of 0.8% in the CABG group versus 2.5% in those with PCI plus stenting. Also, 13% of the patients in the PCI group required additional PCIs, whereas only 4.8% of those in the CABG group needed revascularization at one-year followup.

Overall, however, PCI, prior to drug eluting stents has been shown to be safe and effective. The downside is that long-term outcomes are inferior compared to CABG, there is a need for more revascularization, more symptoms, and a questionable effect on prognosis.

Drug-eluting Stents
Over the last few years, a whole new treatment approach has come to light - coated stents which elute drugs to prevent restenosis. Bare stents now are being coated with a number of different agents in an attempt to inhibitors restenosis. Studies have suggested that the most promising of these, at the present time, are sirolimus (Rapamycin®, Wyeth-Ayerst), a naturally occurring macrocyclic antibiotic which is used as a potent immunosuppressive agent to prevent organ transplant rejection, and paclitaxel (Taxol®, Bristol-Myers Squibb), a well-known anti-metabolic agent used in the treatment of a number of cancers.

In one of the earlier trials (the SIRIUS trial), 1058 patients were randomized to undergo PCI with placement of either bare metal stents or 18mm sirolimus-eluting Bx VELOCITY™ stents (Cordis, A Johnson & Johnson Company). Data analysis pointed out that the overall restenosis rate was approximately 10% in the sirolimus-coated stents versus between 40% and 50% in the uncoated, bare metal stents. Furthermore, the sirolimus-eluting stent prevented neointimal growth and latelumen loss irrespective of lumen size compared to the classical negative relation between vessel size and late lumen loss seen in the vessels which received bare metal stents.

"Does this decrease in restenosis seen with the use of drug-eluting stents improve the patient's prognosis?" Dr. Lytle asked. "Perhaps, but, as yet, this really isn't known since this approach is still in its infancy. Possible problems include a trade-off of no restenosis versus late aneurysms, late restenosis after nine months or more, or activity in restenotic lesions. Finally, the use of drug eluting stents is tied to the size of the blocked segment and the number of stents that might be needed."

©Drug and Market Development 2003

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