NEW YORK – Researchers at Sinai Hospital of Baltimore are collecting information on genetics and other biomarkers from patients who have had cardiovascular events and assessing how this data can be used to improve their outcomes.
They're collecting this data under the banner of a broader study on thrombogenicity hoping to gauge potential differences in blood clotting between Black and White patients. The long-term goal with this research is to lay the groundwork for a multicenter study involving more patients.
The clinical trial, known as Multidisciplinary Approach to Reduce Cardiovascular Health Disparities in the Baltimore RAcial Minority CommunitiEs, or M-BRACE for short, is an observational study primarily enrolling patients admitted to the hospital with atherothrombotic events such as heart attack or ischemic stroke.
Investigators plan to enroll about 300 patients who've experienced cardiovascular events — half of whom are Black and half of whom are White — into this portion of the study. Patients will undergo laboratory tests related to thrombotic risk and other cardiovascular risk factors, and researchers will compile the results into a report that's shared with the patient's physician. The report also includes recommendations for preventing another cardiovascular event, which can include suggested medications and lifestyle modifications.
Investigators follow up with patients three months after these initial assessments for additional blood testing to see how patients are responding to their prescriptions and if there are other medication adjustments to try.
When approaching patients about the M-BRACE trial, investigators explain that as part of standard care, they will be put on antiplatelet medications to reduce the chance of forming another blood clot that can cause a future cardiovascular event. So, it's important that the medication works as it's expected to, said Kevin Bliden, director of clinical trials at the Sinai Center for Thrombosis Research, where the study is based, adding, "there's a lot of variability in how you respond to many medications."
In addition to patients who are recovering from a cardiovascular event, investigators are also studying a second cohort comprising around 75 Black patients who are first- or second-degree relatives of these patients but who don't have a history of hospitalization for cardiovascular or cerebrovascular disease. In these patients, researchers will explore strategies for preventing a primary cardiovascular event.
Investigators are measuring numerous biomarkers within the clinical trial, including markers of inflammation like C-reactive protein (CRP) and D-dimer, as well as urinary thromboxane, a biomarker that the research team has previously shown is associated with cardiovascular disease and can be reduced with medications such as aspirin.
Investigators are also measuring patients' clotting characteristics, such as the speed and strength of clot formations and how well antiplatelet medications are working to prevent them, alongside platelet aggregation, platelet function, and coagulation. In addition, they do a standard lipid panel and test patients' lipoprotein(a) levels, an area of growing interest within the biotech space, which can inform care strategies for lipid management.
Patients do a cheek swab for pharmacogenetic testing to guide antiplatelet prescribing decisions, too. Patients with certain variants in the CYP2C19 gene can't metabolize a commonly used medication, Plavix (clopidogrel), which puts them at risk for another cardiovascular event. These patients could benefit from switching to an alternative P2Y12 inhibitor such as Eli Lilly and Daiichi Sankyo's Effient (prasugrel) or AstraZeneca's Brilinta (ticagrelor). Results from the PGx test are returned within an hour, enabling physicians to make those prescribing decisions quickly before the patient leaves the hospital.
That's all done in addition to a cardiovascular risk assessment of patient-reported information, including their medications, family history, and diet, exercise, and other lifestyle factors.
Within the M-BRACE trial, investigators are primarily interested in the differences in platelet fibrin clot formation and how quickly clots form between Black and White patients based on lab testing done at baseline. They want to better understand race-related differences in thrombogenicity and investigate the genetic and other biological underpinnings of those differences.
It's important to understand how risk factors affect patients of different racial and ethnic backgrounds, Bliden said. "We should try to do our best to see how we can personalize therapy to improve cardiovascular outcomes in the Black population," he added. That's especially necessary in a city like Baltimore, in which 61 percent of the population is Black, according to the latest US Census data. Twenty-eight percent of the population is White.
Separately, as a secondary outcome in the M-BRACE trial, investigators are studying whether patients experience recurrent cardiovascular events after receiving treatment informed by the various biomarkers and patient-reported information shared with physicians, for which they'll monitor patients for up to one year.
Results from this clinical trial will hopefully serve as a "springboard" to identify signals for future research on personalizing therapies, and spur interest in funding a larger study, said Paul Gurbel, principal investigator of the M-BRACE study and director of the Sinai Center for Thrombosis Research.
"It's not large enough to really change practice," he said, reflecting on the aims of the M-BRACE trial, which has enrolled more than 150 patients since its launch in 2023 and will likely run for another year. "It can give us insights into where we may need to go in the future and serve as a basis for obtaining support for larger studies."
The M-BRACE trial is funded by a grant from the Blum Family Foundation in Baltimore.
Gurbel founded the Sinai Center for Thrombosis Research in 1998 to study antithrombotic and antiplatelet therapies and improve cardiovascular treatments. Gurbel and colleagues in 2003 published one of the earliest papers on resistance to Plavix, in which they reported that more than 30 percent of patients undergoing elective coronary stenting didn't respond well to the drug. They also published one of the earliest research papers identifying CYP2C19 pharmacogenomic variants.
Gurbel suggested it's challenging to convince doctors to use biomarkers to personalize existing drugs that are already on the market, in part because there's often little support from the drugmakers that don't want to limit their potential treatment population. He noted that it has taken years from when the first research was published in the 2000s for CYP2C19 genotyping to pick up steam in the US.
"We clearly need to get the translational research done and the message sent out in a shorter period of time than two decades," Gurbel said.
The research team at Sinai Hospital is also collecting patient samples to investigate new, exploratory biomarkers associated with cardiovascular outcomes, for which they don't yet have treatment recommendations.
The M-BRACE team has partnered with researchers at the University of Maryland, which is conducting a genome-wide association study on blood samples, aiming to identify genetic markers linked with heightened thrombogenicity. These markers, if validated in future research, could be used to personalize anticoagulants or antiplatelet drugs.
Investigators are also analyzing several hundred microbiome markers related to gut health, but this is an exploratory analysis, and their discoveries won't yet be shared with physicians and patients.
"We hope in the near future we'll be able to have a panel of these markers that are associated with cardiovascular disease," Bliden said. "But more work has to be done."