Women suffering from cardiovascular disease outnumber men, according to the American Heart Association (AHA; Dallas). And therefore it would make sense then that women must undergo more interventional procedures, right? Not true, according to a panel of experts that last month released a scientific statement calling for improvement in the treatment of female cardiovascular patients and earlier diagnosis and referral to contemporary interventional cardiovascular therapies.
The AHA statement, published in the association's journal, Circulation, addresses the rising rate of mortality in women with cardiovascular disease and urges physicians to provide earlier referrals of women for percutaneous coronary intervention (PCI). Despite the known benefits of interventional procedures such as angioplasty and stenting in reducing heart attacks, only one-third of all patients treated with interventional procedures are female, the AHA says.
PCI, which includes balloon angioplasty and stenting to open blocked arteries, could prevent many coronary heart disease deaths in women each year, particularly in women who arrive at the hospital having a heart attack, according to the statement, titled "Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women." More than 1 million Americans undergo PCI each year, but only 35% of these procedures are performed in women, according to Alexandra Lansky, MD, chair of the statement writing group, director of the Women's Cardiovascular Health Initiative at the Cardiovascular Research Foundation and associate professor of clinical medicine at Columbia University Medical Center (both New York).
Lansky told Cardiovascular Device Update that the reason women are not as often referred for PCI is frequently the product of outdated information indicating that women experienced high death and complication rates as a result of these procedures. Her hope is to draw awareness to the disparities in treatment, she said. "This review finds that these procedures are not only safe and effective in women, but that outcomes continue to improve," she said. "Twenty years have now gone by, and the technology has clearly come a long way from balloons and devices that really didn't work in women." Lansky said older devices were larger, cumbersome and harder to maneuver in smaller vessels. By contrast, she said, today's stent devices, including drug-eluting stents, "are designed for much smaller vessels and are negotiable down small vessels which is particularly relevant for the female patient and can be delivered in a much broader spectrum of lesions."
While modern technology should pave the way for breaking down the referral bias, Lansky acknowledged that research does confirm that the female population may present some "unique problems." She said there is "no question" that women have higher cardiovascular risk profiles. "Typically women who are referred for PCI have smaller vessels; they also have more diabetes and hypertension and are usually eight to 10 years older than men who are referred." She also said that women often delay seeking treatment, so much so that often when they have heart attacks they will seek help from 30 minutes to 60 minutes later than their male counterparts.
Lansky said those factors, rather than gender, contribute to a higher risk of death in women and should not keep women from having potentially life-saving treatments. "A closer look at known clinical data reveals that it is these risk factors, and not gender per se, that is responsible for the poorer results in women. In fact, once women are referred for PCI, the rate of blood vessels being successfully re-opened is similar to that in men."
The AHA statement does not offer specific recommendations for physicians but compiles the latest evidence about the effectiveness of PCI in women. The panel identified three important areas for improving women's treatment. The first recommendation is in the area of diagnosis and early referral for treatment. Women face great delays for stenting or angioplasty, Lansky said. By contrast, men are usually promptly referred for these procedures for suspected cardiovascular disease. Lansky and her colleagues said the goal should be the same for women.
The statement also encourages further research to optimize therapy for patients with diabetes and small vessel coronary disease, two conditions prevalent among women. Finally, the panel calls for more re-fined treatment pathways and strategies for women who have ST-elevation myocardial infarction, a type of heart attack where mortality rates and bleeding risk remain significantly higher than in men.
Noting that the new statement is based on analysis of gender-specific evidence compiled in clinical trials over the last two decades, Lansky said more such trials are needed. "Our statement is based on the gender-specific evidence we have available to us," she said. "To truly improve outcomes in women, we need to recruit more women in future clinical trials, as female representation has been 38%, at best, and often closer to one-quarter of the studied populations."
Before interpreting any clinical trial data, it is always important to examine all risk factors and attri-butes of a certain patient population, Lansky added. Going forward, she said it will be necessary to show "cardiologists and the more general internists that these procedures are safe, save lives, prevent heart attacks and, hopefully, begin to change the referral pattern. It doesn't make sense to withhold these procedures in 2005."
Crawford to remove 'acting' from title
President George Bush said in mid-February that he planned to nominate Lester Crawford to head the FDA. Crawford has served as acting commissioner since March 2004, when Mark McClellan left the agen-cy to lead the Centers for Medicare & Medicaid Services (Baltimore).
Mike Leavitt, the newly named secretary of the Department of Health and Human Services (HHS), which oversees the FDA, called Crawford "an outstanding choice" for the job. "Dr. Crawford has dedicated his career to advancing the nation's public health and will lead the way as we enter a new era of individualized medicine and rapidly developing science," Leavitt said. "With Dr. Crawford's leadership, FDA will provide the world's safest drugs and empower citizens with the tools they need to make informed choices about their health."
Dan Schultz, director of the FDA's Center for Dev-ices and Radiological Health (CDRH), told CDU that removing "acting" from Crawford's title is "extremely important," not because it has anything to do with how seriously Crawford takes his responsibilities but because of public perception.
"People perceive the term 'acting' as something that makes us less able to do what we need to do and move forward with new initiatives," Schultz said. "From where I sit, having somebody I have dealt with and I know [heading FDA] supports the device program and what we are trying to do is a great thing."
Schultz said Crawford has been "very supportive" of CDRH initiatives, including the user fee program. He stressed that the appointment maintains continuity and will keep the center's programs moving forward without delay. "FDA has its strategic plan, [CDRH has a] strategic plan, and my goal is to make those things happen, not to start all over again," he said. "I think we have done enough planning; now is the time to get some work done."
Though Crawford may not be "as dynamic as some other people who have been there in the past," according to Schultz, he said Crawford's understanding of the agency will be critical. "He has a steady hand; he understand the regulatory process; he understands science, and he understands the political process," Schultz said. "I think he is going to do a great job."
Pamela Bailey, president of the Advanced Medical Technology Association (Washington), said in a statement that her organization looks forward to continued work with Crawford and that he understands "the unique characteristics of the medical technology industry. Dr. Crawford's experience will be invaluable as Congress and FDA craft legislation this year that will add predictability and stability to the medical device user fee program and allow for the program's continuation beyond the current fiscal year," she said.
Crawford's nomination comes at a time when the spotlight has been turned squarely on the FDA's drug approval process. The agency has come under fire recently as slow to respond to post-market studies and then been forced to pull some high-profile drugs from the market due to serious health risks. In response to calls for more careful post-market review, Leavitt last month announced the creation of an independent Drug Safety Oversight Board to monitor FDA-ap-proved drugs in order to update physicians and patients concerning emerging information on risks and benefits.
"The public has spoken and they want more oversight and openness," Leavitt said during a meeting with FDA employees at the agency's headquarters in Rockville, Maryland. "They want to know what we know, what we do with the information and why we do it. We will address their concerns by cultivating openness and enhanced independence."
Leavitt said the new group will be comprised of members from FDA, medical experts from other HHS agencies and government departments and will consult with outside medical experts and representatives of patient and consumer groups. The new board is expected to create a drug safety web page with updated information on previously and newly improved drugs, including side effects, safety risks and steps that can be taken to minimize them. Separate information sheets also will be provided for healthcare professionals and patients. "Our goal is to prepare the agency for these new demands by improving the way we monitor and respond to possible adverse health consequences that may arise regarding drugs that have been approved for sale to U.S. consumers," Crawford said in a statement.
Schultz said there is "always room for improvement," but added that FDA staff from every department are concerned with safety. "It has been targeted at drugs so far, but the truth of the matter is that you could apply it to all medical products," he said. "The question is whether you believe that the people who approve products don't care about safety. I have a hard time with that contention. If you believe that, we need a housecleaning and we need a whole new system.
He added: "I think that people within the agency, both on the pre-approval side and the post-market side who care about safety, care about effectiveness, care about getting new products and new technologies to market and come to work every day and try to balance those things."
Crawford's nomination is subject to Congressional approval. While most expect that approval to come quickly, he will likely have to field some tough questions from lawmakers. Sen. Edward Kennedy (D-Massachusetts), ranking member of the Health, Education, Labor and Pensions Committee, for instance, said that the current controversies concerning drug approvals came while Crawford was acting commissioner, and so "it will be important for him to lay out to Congress and the American public his specific plans to ensure the safety of our prescription drugs as well as our food supply."
Crawford received his doctor of veterinary medicine degree from Auburn University (Auburn, Alabama) and a PhD in pharmacology from the University of Georgia (Athens). He has served as administrator of the Agriculture Department's Food Safety and Ins-pection Service and as an adviser to the World Health Organization (Geneva, Switzerland).
Periodontal ills linked to stroke, heart attack
Researchers have found evidence that older adults with higher proportions of four periodontal disease-causing bacteria in their mouths tend to have thicker carotid arteries, a strong predictor of stroke and heart attack, with the results published in the journal Circulation. According to the authors, these data mark the first evidence of a direct link between cardiovascular disease and bacteria involved in periodontal disease, a gum inflammation that affects an estimated 200 million Americans. But the researchers say the findings are not proof that the bacteria cause cardiovascular disease, but may be, rather, a symptom of heart problems. "What was interesting to us was the specificity of the association," said Mo se Desvarieux, MD, PhD, lead study author and an infectious disease epidemiologist at the Mailman School of Public Health of Columbia University and the University of Minnesota. "These same four bacteria were there, they were always there in the analysis and the relationship seems to be pretty much, with one exception, limited to them."
Desvarieux stressed that although the new data further illuminate a long-standing scientific issue, they shed little light on the broader public health question related to cardiovascular disease. The 657 people in the study had their oral bacteria and carotid thickness evaluated at the same point in time. So, Desvarieux said, "It's impossible to know which comes first, the periodontal disease or thickening of the carotid artery." The answer to that question is fundamental to establishing causality in this case, whether chronic inflammation or infection could have led to the atherosclerosis of the carotid arteries.
He and his colleagues noted that the public health information could come soon.
"We will re-examine the participants in less than three years, and, at that point, we can better evaluate the progression of the atherosclerosis and, hopefully, begin to establish a time frame underlying the diseases," said Ralph Sacco, MD, associate chair of neurology, professor of neurology and epidemiology, and the director of the Stroke and Critical Care Division of Columbia University College of Physicians and Surgeons and also a study author.