PFIZER’S decision last weekend to abandon a promising cholesterol drug is but the latest recent setback as the health care industry continues its assault on cardiovascular disease, which has remained the leading cause of death and disability in Western societies since World War I.
Another reminder of the difficulties will come this week in Washington. Thursday will be the first of two days of hearings by a federal advisory panel that is expected to recommend stricter regulation on the use of drug-coated stents, the medical device industry’s most popular tool for dealing with clogged heart arteries.
The panel will weigh evidence that the stents, which were developed to keep coronary arteries open after they have been cleared of plaque, can in some cases cause fatal blood clots months or even years after they have been put in patients.
“From where we sit, there are more questions than answers,” said Dr. Daniel G. Schultz, director of the Center for Devices and Radiological Health at the Food and Drug Administration, which is holding the hearings.
Wall Street is uneasy, too. The nation’s market leader in stents, Boston Scientific, whose stock was struggling under the weight of the company’s $27 billion takeover of Guidant in April, has experienced an additional 7 percent stock decline in the last three months — largely on rising concern among doctors and consumers about the long-term clotting risks.
The nation will spend close to $258 billion treating cardiovascular diseases this year, according to the American Heart Association, including $50 billion on devices and drugs.
But drug and device companies face a shifting landscape in which the traditional image of the heart and circulatory system — pipes and pumps where any clogging is a threat — has been replaced by a far more complicated picture. It is now clear that the human circulatory system can adapt to some types of clogging, but that patients can be killed without warning by the rupture of “vulnerable plaque”: fatty deposits containing a stew of cells that can cause rapid formation of a clot.
So far, though, there is no sure way to locate which plaques are about to rupture. Nor is there a proven drug or device for preventing their formation, dissolving them or sealing them off.
“Technology is pushing against the limits of our knowledge, and we are finding that to a certain extent, things are more complicated than we thought,” said Dr. Barry T. Katzen, director of the Baptist Cardiac and Vascular Institute at Baptist Hospital of Miami.
There are numerous forms of cardiovascular disease, which causes or contributes to the death of 2,500 Americans every day, according to the American Heart Association. While heart attack may be the most obvious dire outcome, symptoms as diverse as swelling of the feet, sexual dysfunction, stroke, kidney failure and chest pains are all common.
The death rate has been falling since the 1960s, a trend driven by the decline of smoking and more attention to healthier diets and lifestyles. But medical technology like heart pacemakers and defibrillators; blood-thinning and anti-clotting drugs; and, more recently, the cholesterol-fighting statin drugs have all helped, too.
Pfizer was chasing a potential blockbuster vision of reversing the progression of heart disease. Its drug torcetrapib stimulates production of a fat-grabbing protein — high-density lipoprotein, or HDL, the so-called good cholesterol. High levels of HDL can reverse plaque accumulation.
In theory, drug companies that are already working on closely related HDL stimulators may achieve torcetrapib’s benefits without its dangerous side effect of raising blood pressure. But Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, who was the lead investigator on an early clinical trial that highlighted the promise of torcetrapib, said researchers might now have difficulty enrolling patients in trials of related drugs. “It might kill the class,” he said.
Stents, meanwhile, are frequently used to relieve the disabling discomfort of angina rather than treat acute heart disease. They were introduced in the 1990s as an enhancement to angioplasty, a procedure in which a tiny balloon is inflated inside a blockage in a blood vessel to create a broader channel for blood flow. Bare-metal stents halved the frequency with which coronary arteries quickly clogged up again at the angioplasty site to about 20 percent.
Drug-coated stents, introduced in the United States in 2003, cut the reblockage frequency in half again and quickly grabbed close to 90 percent of the market because they saved patients the costs and risks of repeat procedures. Boston Scientific’s Taxus and Johnson & Johnson’s Cypher are the only drug-coated devices currently approved for sale, although Medtronic recently asked the F.D.A. to approve its Endeavor stent, and several other potential competitors are also developing products.
But now stent sales are falling in the United States and doctors report numerous calls from patients wondering whether the drug-coated devices are ticking time bombs. The risk may be slight, but it adds up to tens of thousands of heart attacks annually, because 600,000 Americans now receive coronary stents each year. And research suggests that such heart attacks kill as many as half of the patients who suffer them.
So far, the added risks of late clotting appear to balance the added risks of repeat procedures for bare-metal stents. That leaves unsettled the question of which device — the drug-coated or the bare-metal stent — might be safer in the long run.
One contentious issue the F.D.A. panel plans to discuss is the risk, benefit and cost of keeping patients indefinitely on a daily diet of aspirin and the anticlotting drug Plavix, to reduce the late clotting risk. Wall Street will also be watching closely to find out whether the panelists urge the F.D.A. to discourage the widespread “off-label” use of drug-coated devices in groups of patients who are in poorer health than those studied in the clinical trials.
One suggestion has been that the F.D.A. may require longer-term safety data for new stents. Because many of the new designs have features and early data suggesting they may be safer than Taxus or Cypher, however, some experts believe the F.D.A. will end up requiring more rigorous follow-up studies, rather than delay their entry into the market.
The new designs point to a persistent challenge for medical device regulators. Will changing technology render obsolete much of the safety data doctors are clamoring for about today’s devices before it can be compiled?
