The Case For Drug-Eluting Stents Grows Stronger

Introduction
Based on promising results from earlier clinical trials, preliminary findings from studies of new stent coatings, and a cost-efficacy study based on results from a large scale trial comparing drug eluting stents with conventional base metal stents, drug eluting stents appear to be the front runner in the race to solve the major problem of restenosis after success percutaneous coronary interventions (PCI), whether balloon angioplasty alone or stent placement, according to investigators speaking at the 52nd Annual Scientific Session of the American College of Cardiology, held in Chicago, Illinois from March 30 to April 2, 2003.

Cost-Effectiveness of Drug-Eluting Stents
Data from a pharmacoeconomic substudy of the SIRIUS study pont out that the clinical benefits of the sirolimus-coated stent (Cypher™, Cordis, A Johnson & Johnson Company) may justify its initial extra expense, according to David J. Cohen, M.D., Director, Interventional Cardiology Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

The SIRIUS trial randomized 1,058 patients undergoing PCI to either a sirolimus-eluting stent or a bare metal stent, Dr. Cohen explained. Results of the trial, reported in October 2002, demonstrated that patients who received sirolimus-eluting stents had a significant reduction in risk of death, myocardial infarction (MI), or repeat revasculariza-tion of the same artery compared to those who received bare metal stents. Over the one-year followup period, the sirolimus-eluting stent led to substantial reductions in the need for repeat revascularization (19 less events per 100 patients) and hospitalization for any cause (25 less events per 100 patients). As a result, followup medical care costs were $2,500 less per patient with the sirolimus-eluting stent compared with conventional stenting. Initially, the sirolimus-eluting stent had cost $2,000 more than the bare metal stent, for a total cost of $2,800.

Overall, Dr. Cohen continued, the use of the sirolimus-eluting stent increased the initial procedure and hospital cost considerably. The median cost of the initial procedure for patients receiving sirolimus-eluting stents was $7,252 versus $4,395 for bare metal stent placement, a difference of $2,856. When all initial hospital costs were totalled, the difference was still $2,880 in favor of bare metal stenting.

When the costs from hospital discharge to 12 months followup were calculated, however, Dr. Cohen continued, these came to $5,468 in the sirolimus-eluting stent patient compared to $8.040 for those with bare metal stents, a difference of $2,571, favoring the sirolimus-eluting stent.

The total costs, therefore, added up to $16,813 for the patient with a sirolimus-eluting stent compared to an almost identical $16,504 for the patient who received a bare metal stent.

While the difference between the two approaches is not statistically greater, Dr. Cohen stated, the $309 difference can be significant considering that one million patients undergo stenting annually. In the SIRIUS trial, only short stents were available. Now, with longer stents at hand, the cost difference at one year is only $136 in favor of bare metal stents and, if a longer stent is used without clopidogrel (Plavix®, Sanofi Synthelabo/Bristol-Myers Squibb), there is a savings of $96 per patient.

"Although one year costs were $300 per patient higher with the sirolimus-eluting stent," Dr. Cohen concluded, "its incremental cost-effectiveness ratio, based on the $1,700 per repeat revascularization avoided, and a cost per year of Quality of Life (QALY) of only $12,116, compared to the cost per QALY gained of $27,500 in the primary analysis, compares favorably with other accepted medical treatments in cardiovascular medicine. The availability of longer stents and improved implantation techniques should further enhance the cost-effectiveness of this technology in the immediate future."

New stent coatings on the horizon
In a pilot study on the use of angiopeptin-eluting stents (Ysio™DDPC stent, BioDiv), the stent appears to be feasible and safe, with encouraging preliminary efficacy results, stated Vincent On-Hing Kwok, M.D., a staff interventional cardiologist at Grantham Hospital, Hong Kong.

Angiopeptin, a synthetic cyclic octa-peptide analogue of somatostatin, inhibits production of growth hormones such as insulin-like growth factor 1, platelet-derived growth factor and epithelial growth factor. The drug is absorbed onto a phosphorylchlorine "sponge" coating on the stent. The coating, which does not elicit an inflammatory response, acts as a reservoir for drug elution, with an elution duration of over two weeks.

To assess the efficacy, feasibility, and safety on tissue growth of this angiopeptin eluting stents in human native "de novo" coronary lesions, 14 patients underwent intravascular ultrasound-guided stent implantation. The mean clinical follow-up period was 42.8 ± 6.4 weeks, during which time there were no 30-day or 6-month major adverse cardiovascular events (MACE). Low dose (22 ug) angiopeptin-eluting stents resulted in a modest degree of neointimal hyperplasia, but zero binary stenosis. Immediate dose (26 ug) angiopeptin-eluting stents appeared to be even more promising. Tests are now being carried out with a somatostatin analogue--SSTR-1--that is more human-vascular specific.

In a related study, everolimus, a new antiproliferative agent, absorbed into a biodegradable polymer matrix to minimize the inflammatory response, has been shown to be safe, with early efficacy results comparable to that seen with sirolimus, according to Eberhard Grube, M.D., an interventional cardiologist, Sieberg Heart Center, Sieberg, Germany.

In a prospective, randomized, single-blinded study, 27 patients with severe single-vessel disease were randomly assigned to an everolimus-eluting stent and 15 patients to control bare metal stents. At 30 days, all patients in both groups remained free of MACE, while at six months, two patients, one in each group had an adverse cardiovascular event. Also, six-month angiographic studies demonstrated an 88% reduction of in-stent late loss in the everolimus-eluting stent group and an 87% reduction in neointimal volume, compared to the bare metal stent controls.

©Drug and Market Development 2003

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