CardioDX Presents Corus CAD Utility Data in Women; Focuses on Sex Differences Education

NEW YORK (GenomeWeb) – Researchers from CardioDx reported data at the American College of Cardiology's annual meeting yesterday showing that in most cases primary care doctors did not send women with low Corus CAD scores for additional testing to determine if their symptoms were due to obstructive coronary artery disease (CAD).

Researchers led by New York University's Joseph Ladapo pooled data on more than 300 women from the IMPACT-PCP and REGISTRY I studies. These women were seen by 16 primary care providers and were administered the Corus CAD test because they presented with symptoms suggestive of CAD.

In the IMPACT-PCP trial, reported at a medical conference in 2013, researchers compared doctors' treatment strategies for more than 250 patients who had typical and atypical presentations of chest pain, before and after testing with Corus CAD. The study showed that primary care doctors modified their diagnostic strategy in 58 percent of patients, reducing testing for 60 percent of those with low scores and increasing testing for 2 percent.

In the REGISTRY I study, researchers led by Ladapo gauged how primary care physicians referred patients who had non-acute chest pain and other symptoms suggestive of CAD based on Corus CAD results. In this study, published in the American Journal of Medical Quality last year, doctors referred 6 percent of patients with low Corus CAD scores for further testing.

Women in the latest pooled analysis had a mean age of nearly 58 years and a mean Corus CAD score of 10.3. A patient with a score of 15 or less by the 23-gene expression test is considered to have a low likelihood of CAD, while someone with a score higher than 15 is deemed to have a high likelihood.

The study showed that primary care docs referred 4 percent of women with low test scores for further cardiac evaluation, while they referred 83 percent of patients with elevated scores. Women's safety profiles were "favorable" upon follow-up, according to study authors, and the few safety events observed in these studies were not related to CAD.

"The gene expression test demonstrated clinical utility by helping primary care providers rule-out obstructive CAD in symptomatic patients with low [scores], identifying women who would not benefit from further cardiac evaluation," Ladapo and colleagues concluded in the abstract presented at the ACC meeting.

Mandy Welsheimer, 50, of Phoenix, Ariz., has benefitted from the Corus CAD test. Welsheimer has a history of high cholesterol, experiences intermittent chest pains, and comes from a family with a history of cardiac illness. One of her grandfathers died of a heart attack at 56, while the other has a pacemaker. During an annual visit with her cardiologist a few years ago, he suggested she receive Corus CAD based on her medical and family history, and since he couldn't quite pin down the cause of her chest pain even after various workups, such as an echocardiogram and stress tests.

Welsheimer received a very low score from Corus CAD. "My doctor was very happy with the results and didn't order more testing," she recalled to GenomeWeb. "I still have the chest pains here and there, but [the test] just gave me peace of mind. You always wonder because of your family history, is this going to happen to me, and it just put my mind at ease when the results came back."

Women represent a growing portion of the market for Corus CAD. CardioDx has performed more than 100,000 tests since launching it in 2009. Of these, doctors have ordered 55 percent of the tests for women and 45 percent for men.

Using an algorithm that factors in a person's age, sex, and gene expression, Corus CAD is the only sex-specific blood test that helps primary care providers rule out CAD for women, according to CardioDX. CAD – occurring when the buildup of plaque blocks more than 50 percent of the artery – shows up in women approximately 10 years after it does in men and kills more women than it does men.

The disease is difficult to diagnose for women due to atypical symptoms, such as sudden weakness, body aches, burning in the chest, palpitations, or a mild discomfort in the chest, back, or jaw in the absence of chest pain. Due to the challenges in diagnosis, half of all women with CAD die from their first heart attack.

In an aging population – more than 44 million women are older than 55 years in age – CAD is a growing and costly public health challenge in women, requiring more accurate diagnostics. Overall, CAD racks up $195 billion in medical costs and results in more than a million diagnostic cardiac catheterizations each year. In 2008 dollars, medical costs related to the condition stood to triple from $273 billion in 2010 to $818 billion in 2030.

Although the healthcare system spends around $5.9 billion annually on cardiac testing for non-diabetic patients in the US, most of these tests don't increase doctors' diagnostic confidence that women's symptoms are due to obstructive CAD.

Standard diagnostic methods such as cardiac imaging are less accurate for women due to more breast tissue and sex-specific differences in cardiovascular anatomy, CardioDx Chief Medical Officer Mark Monane told GenomeWeb. Since Corus CAD factors in sex, alongside gene expression and age, it uses two different algorithms for men and women.

In the 431-patient COMPASS validation study, Corus CAD had a negative predictive value of 96 percent and a sensitivity of 89 percent for assessing obstructive CAD in patients referred for stress testing by myocardial perfusion imaging. Non-diabetic patients with typical or atypical CAD symptoms enrolled in the trial were tested by Corus CAD before receiving myocardial perfusion imaging, and then got either invasive coronary angiography or coronary CT angiography. The study showed that Corus CAD had better sensitivity than myocardial perfusion imaging (89 percent vs. 27 percent) and a better negative predictive value (96 percent vs. 88 percent).

When CEO David Levison founded CardioDx in 2004, he wanted to address the unmet needs in cardiovascular disease that came to light from interviews with several hundred clinicians. One need was the lack of molecular diagnostics in the cardiac field and another was the challenge in diagnosing CAD accurately, particularly in women. What resulted from that field research was the Corus CAD test, Monane said.

Monane, as well as many other cardiac experts, believe currently available diagnostic tests were developed for men, who have long dominated CAD studies. Keeping this in mind from the start, in the COMPASS study published in Circulation: Cardiovascular Geneticsin 2013,48 percent of 431 patients who received a Corus CAD test were women. 

In recent years, CardioDx has been working to push the message that because women are biologically different from men, they also have different diagnostic needs. Last year, Monane participated in a roundtable discussion in Washington, DC, with academicians, payors, industry representatives, healthcare practitioners, and advocacy groups to consider the diagnostic challenges for women with regard to CAD. The experts agreed that physicians and patients needed to be better educated about sex-specific differences in CAD, and about the availability of genomic diagnostic strategies, such as Corus CAD.

Monane and researchers from Yale University, the Jefferson School of Population Health, and elsewhere enumerated these ideas in a paper published online at the end of February in Population Health Management. "Testing is not something that should be dealt with in a trivial manner," Monane said, highlighting the risks. "Radiation is becoming more and more of a concern in medical imaging, especially because for women [reduction in] radiation is part of their preventative health strategy." 

Last month, the non-profit HealthyWomen and the National Association of Nurse Practitioners in Women's Health joined with CardioDx to launch a patient education campaign called "Spread the Word." The public service announcement, which aired during the month of February on television and radio, told women about how their CAD symptoms might be different form men, how standard tests aren't developed with women in mind, and how they can explore the right testing options. The 30-second announcement doesn't mention Corus CAD specifically. 

CardioDx currently has coverage for Corus CAD from Aetna, Coventry, Medicare, and Medicare Advantage. The company also offers financial assistance to patients without insurance coverage for the test.