Drug-eluting Stent - History

History

The first procedure to treat blocked coronary arteries was coronary artery bypass graft surgery (CABG), wherein a section of vein or artery from elsewhere in the body is used to bypass the diseased segment of coronary artery. In 1977, Andreas Grüntzig introduced percutaneous transluminal coronary angioplasty (PTCA), also called balloon angioplasty, in which a catheter was introduced through a peripheral artery and a balloon expanded to dilate the narrowed segment of artery.

As equipment and techniques improved, the use of PTCA rapidly increased, and by the mid-1980s, PTCA and CABG were being performed at equivalent rates. Balloon angioplasty was generally effective and safe, but restenosis was frequent, occurring in ~30–40% of cases, usually within the first year after dilation. In ~3% of balloon angioplasty cases, failure of the dilation and acute or threatened closure of the coronary artery (often because of dissection) prompted emergency CABG.

Dotter and Melvin Judkins had suggested using prosthetic devices inside arteries (in the leg) to maintain blood flow after dilation as early as 1964. In 1986, Puel and Sigwart implanted the first coronary stent in a human patient. Several trials in the 1990s showed the superiority of stent placement over balloon angioplasty. Restenosis was reduced because the stent acted as a scaffold to hold open the dilated segment of artery; acute closure of the coronary artery (and the requirement for emergency CABG) was reduced, because the stent repaired dissections of the arterial wall. By 1999, stents were used in 84% of percutaneous coronary interventions (i.e., those done via a catheter, and not by open-chest surgery.)

Early difficulties with coronary stents included a risk of early thrombosis (clotting) resulting in occlusion of the stent. Coating stainless steel stents with other substances such as platinum or gold did not eliminate this problem. High-pressure balloon expansion of the stent to ensure its full apposition to the arterial wall, combined with drug-therapy using aspirin and another inhibitor of platelet aggregation (usually ticlopidine or clopidogrel) nearly eliminated this risk of early stent thrombosis.

Though it occurred less frequently than with balloon angioplasty or other techniques, stents nonetheless remained vulnerable to restenosis, caused almost exclusively by neointimal tissue growth. To address this issue, developers of drug-eluting stents used the devices themselves as a tool for delivering medication directly to the arterial wall. While initial efforts were unsuccessful, it was shown in 2001 that the release (elution) of drugs with certain specific physicochemical properties from the stent can achieve high concentrations of the drug locally, directly at the target lesion, with minimal systemic side effects. As currently used in clinical practice, "drug-eluting" stents refers to metal stents which elute a drug designed to limit the growth of neointimal scar tissue, thus reducing the likelihood of stent restenosis.

The first successful trials were of sirolimus-eluting stents. A clinical trial in 2002 led to approval of the sirolimus-eluting Cypher stent in Europe in 2002. After a larger pivotal trial (one designed for the purpose of achieving FDA approval), published in 2003, the device received FDA approval and was released in the U.S. in 2003. Soon thereafter, a series of trials of paclitaxel-eluting stents led to FDA approval of the Taxus stent in 2004. The Xience V everolimus eluting stent was approved by the FDA in July 2008 and has been available in Europe and other international markets since late 2006. It is an investigational device in Japan.