Coronary Angioplasty and Drug-Eluting Stents - Applications of Biotechnology in Cardiovascular Therapeutics - page 305

safety and effectiveness of DES as compared with those of alternative treatments
deserve continued study. The lessons that have been learned and the answers to the
remaining questions will facilitate the development and review of future DES.
In 2008, the FDA issued draft guidelines to aid the development, testing, and
manufacture of DES. Concerned about clot formation in some patients years after
implantation, the agency has monitored the devices closely over the past several
years. Two coronary DES are currently FDA-approved: (1) Cypher (Cordis) and
(2) TAXUS ® (Boston Scientific). The guidance document also assesses the toxicity
of the drug used to coat the stent, both on its own and as part of the complete
product. These stents combine device and drug technology and, as such, the docu-
ment contains expertise and input from two agency centers − the Center for Devices
and Radiological Health and the Center for Drug Evaluation and Research.
The relevance of clinical trial data to the “real world” of clinical practice is ques-
tionable. After EU and USA launches of Cypher and Taxus, several single and multi-
center registries were set up to assess DES effectiveness in a broader range of patient
subgroups. These include e-CYPHER, an internet-based European post-marketing
surveillance targeting 15,000 patients who have received a least one Cypher stent.
Some studies have compared DESs using different drugs. A systematic review
and meta-analysis was performed using indirect comparisons and the evidence
indicates that stents eluting sirolimus are superior to paclitaxel eluting stents in
patients without diabetes but not in patients with diabetes (Stettler et al. 2006 ).
Thus variable factors such as background disease of the patient may make direct
comparison of various stents difficult. The FDA acknowledges that DES are com-
plex products to produce, and it believes that through interaction with the FDA
during development, difficulties with test methodologies, animal studies, and clini-
cal trial designs can be addressed. The future of DES likely involves new stent and
carrier materials, including biodegradable materials and new drugs and biologicals.
The FDA anticipates continued collaboration with physicians, manufacturers, aca-
demic institutions, and professional societies.
Future Prospects for Treatment of Restenosis by DES
Future Role of DES in Management of Cardiovascular Diseases
Use of DES needs to be evaluated in the context of constant reassessment of
treatment of cardiovascular diseases. A randomized trial involving patients who had
objective evidence of myocardial ischemia and significant coronary artery disease,
percutaneous coronary intervention did not reduce the risk of death, myocardial
infarction, or other major cardiovascular events when added to optimal medical
therapy (Boden et al. 2007 ). It means that many heart patients routinely implanted
with stents to open arteries gain no lasting benefit compared with those treated just
with drugs. Although patients with stents to prop open coronary blood vessels, in
addition to being treated with statins and other heart drugs in a 5-year trial, had