Routine testing is needed to locate patients who may not benefit from clopidogrel
Up to 30% of U.S. patients carry genetic variations that reduce the effectiveness of clopidogrel, an antiplatelet medication sold under the brand name Plavix, in preventing heart attacks. These patients can easily be identified through genetic testing, but current guidelines do not have any recommendations to do so. A commentary published in the Journal of the American Heart Association from a group of U.S. and European researchers is now calling for future guidelines to incorporate recommendations for CYP2C19 genotyping, especially for those at a high bleeding risk.[1]
The researchers said the risk to Asian patients is even higher, where 60% carry the CYP2C19 genetic variations that reduce the ability of clopidogrel to prevent major adverse cardiovascular events (MACE) and stent thrombosis after percutaneous coronary intervention (PCI) in patients with a CYP2C19 loss-of-function (LOF) allele genotype. They argue that cardiology guidelines are missing the boat on CYP2C19 genotyping and creating a major patient safety issue for nearly one-third of cardiac patients.
“It’s indisputable that this particular genotype influences the effectiveness of clopidogrel, a very commonly prescribed heart medication. There are data from clinical trials and observational studies to support genotyping and its ability to improve patient outcomes and decrease bleeding risk if you use it to guide therapy," explained lead author Lari Cavallari, PharmD, chair of the University of Florida Health Department of Pharmacotherapy and Translational Research and the Debbie DeSantis Excellence Professor, in a statement. “Many of the barriers that once limited CYP2C19 genotyping in clinical practice have now been removed. The process is similar to other routine laboratory tests we rely on, except this one only needs to be done once.”
The commentary summarizes the evidence that supports CYP2C19-guided P2Y12 inhibitor selection and how it relates the the 2025 American College of Cardiology/American Heart Association/American College of Emergency Physicians/National Association of Emergency Medical Services Physicians/Society for Cardiovascular Angiography and Interventions acute coronary syndrome guideline. That guideline focused on strategies to reduce bleeding risk with antiplatelet therapy, it lacks recommendations related to CYP2C19 genotyping.
“In fact, there are more data now to support genotyping than when the last guidelines provided a recommendation that genotyping could be considered. Yet, there’s less attention on the topic,” Cavallari added.
The commentary notes the well-documented impact of the CYP2C19 loss-of-function alleles on clopidogrel effectiveness. While alternative antiplatelet agents prasugrel and ticagrelor can more effectively reduce the risk for atherothrombotic events compared with clopidogrel in patients with a CYP2C19 LOF allele. However, clopidogrel can reduce bleeding risk without an increase in atherothrombotic events compared with these newer drugs in patients without the genetic loss-of-function allele.
In 2024, the American Heart Association created a scientific statement supporting CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed, but the researchers want to see this become an official recommendation in the acute coronary syndrome guideline.
Previously, this type of genetic testing was not widely available, but many commercial laboratory vendors now offer it as a service. In addition, this testing is now covered by insurance in most states. Some states even have now legislation requiring insurers to cover biomarker testing.
The authors noted that the U.S. Food and Drug Administration recently approved a rapid genotyping platform with test results available in approximately one hour.
Cavallari helped expand access to pharmacogenetic testing as director of the UF Health Precision Medicine program, establishing it as a standard of care across UF Health practices in order to identify patients who need alternative drug treatments to avoid complications due to ineffective therapy.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]