No Repeat Stenosis

Breakthrough technology offers long-term, low-risk solution to CAD

By Michelle Ciriacruz

The potential for restenosis or renarrowing of the artery is always a big consideration for coronary artery disease (CAD) patients who have been treated with balloon angioplasty procedures. The buildup of fatty deposits or the growth of scar tissue at the artery wall disturbed by the placement of the stent causes 20 to 30 percent of the patients to undergo repeat angioplasty within six months of the initial procedure.

    With more than 1.3 million people undergoing balloon angioplasty worldwide each year, repeat procedures add up considerably to these patients' worry and health care costs.

    Although balloon angioplasty and stenting do open up blocked arteries, the presence of a foreign material inside the vessel induces an overgrowth of the smooth muscles cells around the device (neointimal proliferation), which leads to reblockage in some cases.

    Improving the stents' design added to flexibility but did not solve the problem of in-stent restenosis. The space freed up by the implanted stent was still being lost with disturbing frequency due to neointimal proliferation. The use of drugs to check the growth of cells was also not successful because of their cytotoxic effect on the arterial wall, which could lead to late thrombosis, necrosis, or more scarring.

    For a long time, since the first stent implantation in 1986, CAD treatment was subject to this exasperating problem. Not until Johnson & Johnson hit upon the right combination of methods did a way out appear.

    It seemed to lie in the integration of a controlled-release drug with cytostatic action on a stent platform. Unlike other drugs with antiproliferative properties, Sirolimus only prevents the replication of cells and does not kill them. It also reduces cytokine production and inflammatory cell activity in the vessel wall.

    Dr. Fabio Enrique Posas, chair of cardiovascular research at the Saint Luke's Heart Institute, explains: "They (Johnson & Johnson) have married the scaffolding-the stent-with a drug that can be delivered through the stent, such that they can deliver higher amounts of drug at the area where we need it without incurring the side effects of high doses that you would normally have to [contend with] if you were to take the medicine orally."

    Mounted as a two-layer polymer on the BX-stent platform, which has a unique closed-cell FlexSegment design proven to have good radial strength for maintaining an unrestricted blood flow within the vessel, Sirolimus is released over a period of four to six weeks steadily in a controlled manner directly upon the site of the vascular injury, ensuring better drug concentration.

    Sirolimus is actually a naturally occurring antibiotic marketed by Wyeth Pharmaceuticals under the name Rapamune. It is used as an immunosuppresant in renal transplant patients.

    The stent has to be first inserted into the affected artery, however. A catheter, threaded over a guide wire through the femoral aorta via a percutaneous puncture beside the groin, is positioned to where the artery originates just above the heart. Using fluoroscopy and the injection of a contrast material, the constriction caused by blockage is revealed for inspection. A balloon attached to the catheter is inflated at the diseased site. This distends the artery; a wire mesh or stent is then deployed to keep the arterial walls from collapsing back into itself.

    This procedure actually just harnessed old technologies but married them to a scaffold with no recoil propensity and a gentler record with vessel trauma, and a drug coating delivered where it can be the most effective.

    Following its approval for medical use by the Bureau of Food and Drugs, Johnson & Johnson Medical Philippines introduced the entire contraption in the country last August 28 as the Cypher Sirolimus-eluting Stent. Cypher is already approved in Europe for de novo procedures.

    However, the first in the world to have received the Cypher stent with previous arterial lesions already treated with conventional angioplasty was well-known economist and journalist Hilarion Henares. His emergency procedure using Cypher last May 23 actually facilitated its formal release in the country.

    Backed up by the RAVEL (RAndomized Study with the Sirolimus-eluting VELocity Balloon-Expendable Stent) and SIRIUS studies, the use of the Johnson & Johnson coated stent resulted in a dramatic reduction of reblockage (within the stent)-at 98 percent, zero mortality, and no further requirement for angioplasty and bypass.

    The RAVEL study involved 238 patients with single de novo lesions in 19 centers across Europe and Latin America. One hundred eighteen of the patients received a conventional Bx stent, and the rest treated with the Sirolimus-eluting stent. At 12 months into the study, 94 percent of the Sirolimus-treated cohort were not seen with complications due to the reduction of restenosis, as opposed to the 7-percent event-free survival rate for patients in the control arm of the study. There was also no evidence of blood clot formation despite the discontinuation of antiplatelet therapy after just two months.

    Data from the SIRIUS study, a large-scale US trial involving 1,101 patients and 53 US hospitals, verify these findings-which essentially mean shorter hospital stay, faster recovery, less need for reintervention, and virtual elimination of the need for open heart surgery for the patients.

    These outcomes Mr. Henares swore to, saying that right after the procedure, he has never felt better, going about his normal business just a few days following.

    Says Dr. Posas: "In the future, this opens the door for adding more drugs that would increase the healing of the vessels." He predicts that, eventually, heart bypass will only be performed on individuals with extreme CAD, in whom these interventional procedures just cannot be performed.

    The Wall Street Journal also noted this likely development. "Some experts predict that 30 percent and perhaps as many as half of bypass patients-more than 500,000 in the US each year-might now be treated with the less invasive procedure."

    Those interested in more information about balloon angioplasty using the Cypher Sirolimus-eluting Stent can approach cardiologists in the following hospitals: Asian Hospital and Medical Center, Chinese General Hospital, Makati Medical Center, Philippine General Hospital, Philippine Heart Center, St. Luke's Medical Center, The Medical City, and the University of Santo Tomas Hospital.