Cardiology Breakthrough

When Shamci Ghaffari was diagnosed with a blocked right coronary artery in 2001, her doctors used conventional treatments to clear the blockage. But within a few months, it was evident there was a problem: the vessel couldn't seem to remain open for more than three weeks at a time.

Though devastating, there was a silver-lining in the situation. Ghaffari's condition developed just as a ground-breaking medical technology was being evaluated as a way to treat coronary artery disease. The timing of Ghaffari's heart problems gave her the potentially life-saving opportunity to take part in the clinical trial of a revolutionary medical technology-one that promises better results for patients and significant savings in the costly battle against coronary artery disease.

Ghaffari's 17-month ordeal began in February 2001 with shortness of breath, chest pain and intense pressure in her left hand. She had always been active, never smoked, and never tasted alcohol in her life. Still, Ghaffari had a family history of heart disease, and though she didn't know it, her condition had been worsening for some time. A stress test indicated the 54-year old bank executive from Boston had a blockage in her right coronary artery, so her doctor scheduled an angiogram to get a better look at the problem.

Before her scheduled appointment, though, Ghaffari's son, a resident at Boston's Brigham and Women's Hospital at the time, found his mother at home with severe shortness of breath and took her immediately to the emergency room.

Doctors performed a number of tests and discovered Ghaffari's right coronary artery was almost completely blocked. They implanted two bare metal stents-expandable wire mesh tubes that are inserted in the artery with a catheter and guided to the blockage through an incision in the leg. Stents help prop arteries open, typically after they have been cleared by angioplasty, when a balloon is attached to a catheter and expanded at the site of the blockage, pushing the fatty build-up into the artery's walls and improving blood flow.

After the stents were implanted, Ghaffari was in constant pain. "I explained it to my doctor that normally, you don't feel your heart in your chest. But I felt it constantly," she says, noting that the intensity of pain varied, but it never went away. In November 2001, Ghaffari was crossing a street in Boston when she nearly collapsed. When she got to the hospital, doctors discovered that a blockage had developed between the two stents, so they implanted a third stent to correct that problem and also used radiation to treat the site, hoping it would inhibit further blockage.

Ghaffari continued to experience pain and shortness of breath. Then in April 2002, she was back in the emergency room; the stents had become blocked again. "The only thing they could do was balloon the stent. But three weeks later, the pain would come back. Between April 4 and July 1, they ballooned the stents five times," she says.

That's when Ghaffari's physicians enrolled her in a clinical trial involving a breakthrough stent specifically designed to prevent reblockage of arteries after implantation. On July 1, physicians implanted an advanced drug-eluting stent coated with a special polymer and drug that slowly released the drug to the surrounding tissue. The drug stopped the growth of cells that caused her repeated blockage problems.

Since that procedure, Ghaffari has had no problems with repeat blockages in the treated artery. The burden of repeated costly and emotionally-draining-but ineffective-treatments has been lifted. The supervisor of commercial loan officers at Fleet Bank is back at work, walking two hours a day, and regularly hitting the gym for an afternoon workout.

The culmination
Like so many advances in medical technology, the development of drug-eluting stents is the culmination of hard work and the commitment to continually improve existing technologies. In this case, balloon angioplasty and bare metal stents are key precursors to the drug-eluting stent.

Coronary artery bypass surgery-during which a physician removes a portion of an artery in the patient's leg and uses it to create a new route for the blood to travel through the heart-has been commonly used to treat blocked arteries. Angioplasty offers a minimally invasive, lower cost-approximately $12,000 ¹ v. $27,000 ² for bypass surgery-alternative to this surgical treatment.

By itself, though, angioplasty results in a high rate of restenosis, or renarrowing of the treated vessel. Approximately one-third of patients will experience reblockage within about six months.³ That's because the procedure over expands the vessel, causing it to recoil too much, promoting the formation of scar tissue and often resulting in renarrowing.

Stents were developed to reduce the incidence of renarrowing by propping the vessel open with their scaffold-like structure. Now, 70 to 90 percent of interventional procedures to clear blocked arteries include stenting.⁴

Still, bare metal stenting presents problems. Very often, the body's reaction to the stent is the proliferation of smooth muscle cells. The metal causes the vessel to respond and the result is scar tissue-like growth within the walls of the stent that blocks blood flow. That is likely what happened to Ghaffari, and it is common among patients with bare metal stents.

"Patients who develop early and repeated narrowing after a successful stent placement have a high probability that the vessel will ultimately close. That can result in ongoing chest pain, or, in some cases, in heart attack," says Dr. Jeffrey Popma, director of interventional cardiology at Brigham and Women's Hospital in Boston. Although coronary bypass surgery is an option in such patients, it involves serious risks, Popma says.

Bypass surgery requires the surgeon to make a major incision in the chest, split the breast bone, and in most cases, stop the heart and route the patient's blood through a heart-lung machine. Removing a portion of an artery from the patient's leg for the bypass also requires a major incision. Patients typically stay in the hospital for five to six days, spend approximately three weeks recovering and usually do not return to work until four to six weeks after surgery.⁵ Because of these issues, physicians like to avoid bypass surgery if possible, says Popma.

Reducing reblockage
By the mid-1990s, problems with reblockage in stented arteries prompted researchers to begin work on a technology that would reduce the high restenosis rate experienced with bare metal stents. Scientists discovered that one of the best ways to prevent renarrowing was to coat bare metal stents with a drug that inhibits cell growth. On April 24, 2003, the Food and Drug Administration (FDA) granted marketing approval for the first drug-eluting stent-the CYPHER™ Sirolimus-eluting Coronary Stent developed by a Cordis Corporation, a division of Johnson and Johnson Co.

Clinical trials conducted on the drug-eluting stents show great promise. "Overall, these results translate to a dramatic reduction in the need for retreatment," says Dr. Martin B. Leon, M.D., a principal investigator in the U.S. clinical trial for the CYPHER Stent from Lenox Hill Hospital and Cardiovascular Research Foundation in New York, New York.

"The 12-month clinical findings indicate that patients who receive the CYPHER Stent have a greater than 95 percent chance of avoiding retreatment, compared with an 80 percent chance for patients receiving a conventional bare metal stent," Dr. Leon says.

Dr. Leon adds that one year after implantation, 91.7 percent of patients treated with drug-eluting stents were free of death, heart attack or retreatment, while 77.4 percent of patients treated with the bare metal stent experienced the same outcome.

Longer term studies show similar results. A clinical trial involving 238 patients in Europe and Latin America, shows that two years after treatment only three patients needed reintervention. And the first patients to receive the advanced technology-a group from Sao Paulo, Brazil-show equally impressive outcomes: "Of the 30 patients with three-year follow-up, there have been no new coronary events in the past year. The results continue to hold with 93.3 percent event-free survival," says Prof. J. Eduardo Sousa, Professor of Interventional Cardiology, Dante Pazzanes Institute, Sao Paulo, Brazil.

One time, and one time only
Jeffrey W. Moses, M.D., of Lenox Hill Hospital in New York was a principal investigator in the U.S. clinical trials for the CYPHER Stent. "Our goal is to treat a blockage one time, and one time only," Moses says. "This is our patients' expectation. Now we have a treatment that can significantly reduce the incidence of reblockage, potentially sparing tens of thousands of patients the need for repeat interventions, including bypass surgery."

In the U.S. the direct medical cost of treating coronary heart disease in 2001 was estimated at $53.4 billion.⁶ Bypass surgery and stented angioplasty account for an estimated $15 to $20 billion of that sum.⁷ Creating an environment where one-time treatment is the norm would mean big savings for health care payers.

David J. Cohen, M.D. of the Harvard Clinical Research Institute conducted independent economic analysis of the U.S. clinical trial involving the CYPHER Stent. Cohen found that the technology was cost-effective at one year and will enable payers to recoup virtually all costs associated with the stent within 12 months. Cohen's analysis showed that for every 100 patients treated with the drug-eluting stent, there were 19 fewer revascularizations, or retreatments, and 25 fewer hospital admissions than with the conventional stent, generating significant post-treatment savings.

In an unusual move that shows the value of the technology, the U.S. Department of Health and Human Services acted before FDA's announcement of marketing approval of the first drug-eluting stent and adjusted its payment schedule to reflect the incrementally higher cost of the advanced technology.

For health care professionals, payers and particularly patients, the availability of drug-eluting stents is likely to transform the environment for treating blocked coronary arteries. Physicians can expect their initial attempts to clear arteries will succeed-allowing them to avoid further procedures, or more invasive treatments like coronary bypass. Payers can expect to pay for just one artery-opening procedure-not a succession of repeat procedures or costly bypass surgery. Patient time in the hospital is reduced and some of these procedures are now being done on an outpatient basis - a long way from the many days in the hospital resulting from bypass surgery.

And most importantly, patients can expect to undergo treatment once, then return to living active, productive and optimistic lives, just as Shamci Ghaffari has done. Always an active person prior to her heart problems, Ghaffari was unable to walk or exercise after her initial stent implant. Between April and June 2002, she was unable to work. "It was sad. It was depressing. I would look around, look at my two sons and think that I didn't have much time with them," she says. Now that she's back at work, walking and exercising again, Ghaffari doesn't think that way anymore.

¹ "Acute and Long-term Cost Implications of Coronary Stenting," by Peterson, et.al., Journal of the American College of Cardiology, vol. 33, No. 6, 1999

²  "Minimally Invasive Cardiac Surgery," by William R. Mayfield, M.C., Peachtree Cardiovascular and Thoracic Surgeons, PA, www.hsforum.com

³ American Heart Association, "Stenosis and Restenosis of Coronary Arteries" available at: http://www.americanheart.org/presenter.jhtml?identifier=4706

⁴ American Heart Association, "Stent Procedure" available at: http://www.americanheart.org/presenter.jhtml?identifier=4721

⁵ "Minimally Invasive Cardiac Surgery," by William R. Mayfield, M.C., Peachtree Cardiovascular and Thoracic Surgeons, PA, www.hsforum.com

⁶ American Heart Association, 2001 Heart and Stroke Statistical Update, Dallas, Texas: American Heart Association

⁷ "The Technololgy" section, Cordis-provided template on drug-eluting stent

July 2003