After more than two years of clinical data linking drug-eluting stents (DES) with an increased risk of stent thrombosis compared to their bare-metal cousins, a study in the Journal of the American Medical Association (JAMA) may shed some positive light on the DES space.

According to the study, published in the June 25 issue, the widespread use of DES is associated with a decrease in the need for repeat procedures to unblock coronary arteries without an increased risk of death, compared to bare-metal stents (BMS).

"This large observational study is better powered than were prior randomized studies to detect the consequences of a difference in stent thrombosis rates between drug-eluting and bare-metal stent recipients, and it may better reflect real-world use of these devices, including for off-label indications," Howard Herrmann, MD, said in Journal Watch Cardiology.

Herrmann noted that an increased risk for late stent thrombosis has been associated with DES in some studies. However, he said, "If such an increase occurred in this study, it was more than offset by a decrease in the risk for restenosis and events arising from its treatment."

David Malenka, MD, of Dartmouth-Hitchcock Medical Center (Lebanon, New Hampshire), and colleagues performed the study to compare the rates of revascularization, heart attack and survival, before and after the availability of DES. The study included 38,917 Medicare patients who underwent non-emergency coronary stenting from October 2002 through March 2003 when only BMS were available and 28,086 similar patients who underwent coronary stenting from September through December 2003, when 61.5% of patients received a DES and 38.5% received a BMS. Follow-up data were available through December 2005.

Only one DES the Cypher from Cordis (Miami Lakes, Florida), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey), was approved for sale in the U.S. in 2003, during the time period of the study's DES-era group. Boston Scientific's (Natick, Massachusetts) was approved in 2004.

Both the Taxus and the Cypher while initially rushing to about $5 billion in combined sales have experienced declining sales as the result of negative clinical data, and a series of reports raising questions about the overall value of DES devices.

During the two years of observation, 22.8% of patients in the BMS-era group received a repeat procedure to unblock coronary arteries. In comparison, only 19% of the DES-era group underwent a repeat revascularization, a decrease of about 18%, the authors noted.

The overall death risks at two years were the same for both groups, 8.4%, but there was a slight decrease in heart attacks from 2.4% to 2%.

"Although such an analysis will not answer the question of what is the true rate of stent thrombosis with drug-eluting stent vs. the rate with bare-metal stent, it does address the important question of whether, on-average, the population of stented patients is being helped or hurt by the widespread use of this technology," the authors wrote.

"Although other data may suggest some incremental risk of stent thrombosis with the use of drug-eluting stents, we can detect no adverse consequence to the health of the population. We speculate that whatever the increased risk of stent thrombosis associated with drug-eluting stent use is, it is more than offset by a decrease in the risk of developing restenosis [renarrowing of a coronary artery after angioplasty] and the attendant risk of a procedure to treat that restenosis."

The National Institute on Aging and the Robert Wood Johnson Foundation (Princeton, New Jersey) paid for the study.

Another recent study, this one reported in late May by researchers from the University of Pennsylvania School of Medicine (Philadelphia), also helped ease DES fears by finding that patients who receive a DES are less likely to die, have a heart attack, or require follow-up surgery than those who receive a BMS. The findings, published in the Journal of the American College of Cardiology, showed a "clear, lifesaving benefit of drug-eluting stents compared to bare-metal stents" among elderly patients in the two years following placement of the stent.

Given the roll-out this year of second-generation DES devices, the study could indicate an even greater benefit of the newer coated stents, which appear to have reduced risks compared to the first generation.

Medtronic (Minneapolis) received FDA approval for its Endeavor DES in February, making it the first in the DES 2.0 family of these devices to win approval. The Xience stent from Abbott Laboratories (Abbott Park, Illinois) is expected to be the next to win approval, having received a positive panel recommendation in early December 2007.

More applications, but approvals flat

The Office of Device Evaluation (ODE) at FDA's Center for Devices and Radiological Health published its report for 2006 and 2007 late last month, and one of the take-aways is that while the agency took in about 9% more applications and submissions related to devices, the number of PMAs and 510(k)s making it through the agency pipeline is flat, at best.

The numbers come at a time when investment in device development has grown steadily, but FDA funding has generally not kept pace with its mission despite user fees. Device makers have complained that they get little value for their user-fee dollar, but the agency faces a now-legendary set of distractions, and may get yet another new commissioner in January.

According to FDA's count, ODE took in 9,276 "major submissions" in fiscal 2007, a category that includes PMAs and PMA supplements and applications for investigational device exemptions and related supplements. Other filings included in that total are 510(k)s, requests for device reclassification, and humanitarian device exemptions and related supplements (the numbers for 2004 and later do not include applications made to the Office of In Vitro Diagnostics).

The number of major submissions was down from 9,415 the previous fiscal year, but in fiscal years 2004 and 2005, ODE examined roughly 8,500 and 8,700, respectively, so the load at ODE has risen, as the rising level of investment in devices over the past few years suggested it would.

One of the more interesting trends in the numbers at ODE is the lack of a trend regarding PMAs, which jump around quite a bit. Starting in 2004, the annual figures for PMA filings are 37, 43, 25 and 31. In marked contrast, the number of PMAs granted has held steady over that same period, starting in 2004 at 29 approvals, then dropping by one each of the following years. In 2007, FDA granted another 27 PMAs, but also rejected seven and wrote approvable letters for another seven (applications that carry over from one year to the next can create mismatches).

PMA supplement filings were all over the map, numbering 565 in 2004 and rising to 712 in '05 and more than 1,100 the following year. That total tapered off slightly to 1,087 in 2007.

Over that four-year stretch, applications for investigational device exemptions (IDEs), trended fairly stably, starting out at 222 in 2004 and ending up at 211 three years later. The highest year of the four, 2006, included 251 IDEs.

FDA's performance numbers during this time were mixed, but while the final numbers are not in for 2007, the duration of time for all types of applications seems to be trending down slightly.

The average total agency review time for PMAs and PMA panel-track supplements fell to 283 days in 2006 from a six-year high of 366 the previous year. However, that average review time of 283 days was identical to the same measure in 2001. The best year, 2003, yielded an average time of 229 days.

Physicians push for healthcare overhaul

Doctors are taking a lead in efforts to heal the ailing U.S. healthcare system with a proposal for a single-payer insurance program that mimics Medicare.

More than 47 million Americans are uninsured and millions others have suffered healthcare-related financial ruin. Fifty percent of all bankruptcy filings were, in part, the result of medical bills yet 68% of those who filed for bankruptcy had health insurance, according to the journal Health Affairs.

Physicians across the U.S. are joining forces in support of a bill in Congress, H.R. 676, which embodies the single-payer approach and has 90 co-sponsors, more than any other health reform proposal in history.

"We have a very expensive, privately funded financing system for healthcare, with very few cost controls built in," John Geyman, MD, professor emeritus of family medicine at the University of Washington (Seattle) and past president of Physicians for a National Health Program (PNHP; Chicago), told CD&D.

"Our private insurance industry has 1,300 insurers, with 15% to 30% of healthcare dollars. The overhead of traditional Medicare is 2% to 3%. It's not for profit," Geyman said. "The private insurance industry is investor-owned, for profit, and services its shareholders. The average family of four spends over $12,000 a year for healthcare and gets less and less. We figure we would save $350 billion a year, or $2,300 a person, with publicly financed Medicare for all, due to administrative simplification, bulk purchasing, improved access to preventive services and earlier diagnosis, basically getting rid of a very inefficient private insurance system."

PNHP includes more than 15,000 physicians who support a single-payer national health insurance program that's represented in H.R. 676, a bill introduced by Rep. John Conyers Jr. (D-Michigan) in January 2007. It was referred to, and remains with, the Subcommittee on Health.

Lest anyone start using the "S" word i.e., socialized medicine Geyman answers: "It's not socialism. The current Medicare system isn't socialized medicine. It's a private delivery system with public financing. This would also be a private delivery system with public financing. Nobody complains about Medicare."

However, political opposition to this potential dramatic shift is huge.

Despite the apparent opposition, device and drug companies, medical suppliers and insurers could do "just fine" with a new, one-payer system, Geyman said, because they still would have to compete for a single, very large market: 300 million Americans in a risk pool with healthcare for all.

"Half of American can barely afford healthcare, medical bankruptcies are going up all the time. The only way to get a handle on this is to move to a public financing system," said Geyman, who is the author of six books, including the forthcoming Do Not Resuscitate: Why the Health Insurance Industry is Dying, and How We Must Replace It.

"Over the past 40 years, private insurance has evolved from a not-for-profit activity into a $300-billion-a-year, for-profit, investor-owned industry," he said. "The six biggest insurers made over $10 billion in profits in 2006. They did so by enrolling healthy people, denying claims and screening out the sick, who increasingly are being shunted into our beleaguered public safety net programs."

When asked to compare a potential U.S. single-payer system to Canada's publicly funded healthcare system, where most services are provided by private entities, Geyman pointed out that Canada's government pays little more than half of what U.S. citizens do for healthcare on a per-capita basis.

Intensive blood sugar effort can be bad

Intensively targeting blood sugar to near-normal levels in adults with Type 2 diabetes at especially high risk for heart attack and stroke does not significantly reduce the risk of major cardiovascular events, such as fatal or nonfatal heart attacks or stroke, but increases risk of death, compared to standard treatment.

Researchers from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) clinical trial compared a medical strategy aimed at near-normal blood sugar levels below current recommendations to a strategy to reach more standard blood sugar levels. Supported by the National Institutes of Health, the study evaluated the effects of intensively targeting blood sugar control among adults with established diabetes, high blood sugar levels, and pre-existing heart disease or at least two cardiovascular disease risk factors in addition to diabetes.

The first published results of the ACCORD trial of more than 10,000 participants appeared last month in the New England Journal of Medicine (NEJM). The results were presented at the American Diabetes Association's (Alexandria, Virginia) 68th annual Scientific Sessions in San Francisco on June 10. In February, the NIH's National Heart, Lung and Blood Institute (NHLBI) stopped the intensive blood sugar strategy after an average of 3.5 years of treatment, instead of the planned 5.6 years, due to safety concerns.

The intensive strategy group had a 22% higher risk of death or 54 more deaths compared to the standard group. The increased risk began emerging within 1 to 2 years after the strategy began to aggressively lower the participants' blood sugar levels. All participants now follow a medical strategy to reach the standard blood sugar levels while other components of the study continue.

"ACCORD is providing important evidence to help guide treatment recommendations for adults with established Type 2 diabetes who have had a heart attack or stroke or who have two or more risk factors for cardiovascular disease in addition to diabetes," said NHLBI Director Elizabeth Nabel, MD. "For these individuals, intensively lowering blood sugar to near-normal levels appears to be too risky."

The researchers caution that the results might not apply to patients who are at lower risk of cardiovascular disease than the ACCORD participants or to patients with more recently diagnosed Type 2 diabetes. On average, ACCORD participants had been diagnosed with diabetes for 10 years at enrollment.

California groups align to boost life science

The Southern California Biomedical Council (SoCalBio; Los Angeles), BIOCOM (San Diego) and BayBio (South San Francisco), which together represent life science firms and research organizations across California, reported an alliance to promote the state's life science industry.

The California Life Science Alliance is based upon a memorandum of understanding signed at last month's 2008 BIO International Convention in San Diego. Under the three-year agreement, the organizations will pool resources and work together to address a range of public policy issues.

The new alliance recognizes that California is the "birthplace of biotechnology and the undisputed leader in global biocommerce and innovation." But while the life science industry is one of the state's largest employers and economic catalysts, it has not garnered its fair share of visibility and recognition, according to the organizations.

"Citizens and elected officials tend to understate our industry's vast contribution to California's economy and society as a whole," said Joe Panetta, president/CEO of BIOCOM. "By working together as an alliance, we can make sure that our representatives in Sacramento and Washington, as well as the public at large, understand that the life science industry is vital to California's future."

With more than 200,000 employees at about 5,000 establishments that generate more than $70 billion in revenues, California's life science firms and research organizations represent nearly half of the world's biotechnology industry, the groups noted. They employ a large workforce and generate a financial impact rivaling that of other sectors such as film and television production, which is routinely heralded as one of California's most important signature industries.

"For too long, California's biotech industry hasn't been recognized for its economic impact, as well as its role in shaping the future of healthcare. The alliance announced today will help remedy this problem," said Matt Gardner, president/CEO of BayBio.

The alliance will focus on public policy and joint advocacy efforts at the state and federal levels. The three organizations will also collaborate on life science industry conferences and joint purchasing group opportunities.

"Regions throughout the world are aggressively trying to lure our biotech firms and the clean, high-paying jobs that go with them," said Ahmed Enany, president/CEO of SoCalBio, which represents the life science and medical device industries throughout the greater Los Angeles area. "Raising the visibility of this vital industry will help Californians understand that California must work proactively to retain its leadership in biotech innovation and commercialization.