Why antiplatelet medication fails some patients and how genetic testing helps

Plavix is the most commonly prescribed antiplatelet medication, yet it’s not effective for everyone. New research shows the reason: a genetic variant that affects how patients metabolize the drug. These patients face a much higher risk of recurrent cardiovascular events.

David Kann, MD, MPH

The American Heart Association recently published new guidance recommending genetic testing before prescribing Plavix. The Gene Health Project at WellSpan Health is making this lifesaving testing available to patients in our community at no cost.

“The project makes genetic testing accessible to everyone. When patients get tested, it gives their providers critical information to guide their care,” says David Kann, MD, MPH, medical director of Precision Medicine at WellSpan Health. “Their genetic information will show, for example, whether Plavix is right for them or whether another antiplatelet medication would be safer.”

Why Plavix works for some patients and not others

Plavix (clopidogrel) is a prodrug, which means it needs a specific enzyme (CYP2C19) to work in the body. About 30% of Americans have genetic variants that reduce or eliminate this enzyme's activity. As a result, they can’t activate Plavix effectively, even when they take it exactly as prescribed.

Choosing antiplatelet treatment based on genetic testing results

Genetic testing is a step forward in precision medicine, allowing providers to use patients’ genetic information to guide treatment decisions. Providers can choose antiplatelet therapy based on patients’ CYP2C19 genetic variant status:

• Ticagrelor (Brillinta) and prasugrel (Effient) are among the safe, effective alternatives for patients with the genetic variants that inhibit Plavix metabolism.
• Patients who don’t have those genetic variants can take Plavix.

“Genetic testing helps us tailor antiplatelet therapy so patients get the medication that’s truly effective for them,” says Kate Cummins, PharmD, pharmacogenomics pharmacist at WellSpan Health. “That kind of precision can help prevent repeat heart attacks and strokes.”

New AHA guidance: Genetic testing before prescribing Plavix

In 2024, the American Heart Association issued a scientific statement recommending CYP2C19 genetic testing for any patient who is taking or may need Plavix (Pereira et al. 2024). The goal is to help providers choose the antiplatelet therapy that will offer the strongest protection for each patient. A one-time genetic test can provide lifelong information to guide treatment decisions now and in the future.

How your patients can access no-cost genetic testing

Because genetic testing can be expensive and difficult to access, many patients don’t get tested, despite the AHA statement. WellSpan Health offers genetic testing at no cost for anyone over 18 through The Gene Health Project.

The project tests for three hereditary conditions: familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. But the genetic data offer much more — they can guide medication decisions for years to come.

“Once a patient is sequenced, we can use that data again and again,” says Dr. Kann. “It’s what we call ‘Sequence Once, Query Often,’ allowing us to revisit that genetic information as new therapies or questions come up.”

Testing includes full exome sequencing through WellSpan Health’s partner, Helix, a population genomics company. Helix stores patients’ results securely, and a patient’s authorized health care providers can access them when needed throughout the patient's lifetime. When your patients enroll, their genetic information becomes available for future medical decisions — beyond which blood thinner will work best.

What’s ahead in pharmacogenomics

The Plavix finding is just one example of how genetic information can improve everyday prescribing decisions. WellSpan Health’s pharmacogenomics team is now expanding this work into other medication categories, such as behavioral health.

Gene-drug interactions with antidepressants, antipsychotics and ADHD therapies can strongly influence side effects, dosing and treatment response. That could mean months of trying different medications to find the right one. Genetic testing allows providers to identify the right medication from the start.

“Our goal is to support primary care and other specialties in getting patients tested ahead of time,” says Dr. Cummins. “When we have the genetic information up front, we can guide safer prescribing and help patients reach effective treatment faster.”

As more data become available, pharmacogenomics will continue to shape how we think about prescribing, not just for cardiology and behavioral health, but across many areas of medicine. By encouraging patients to join The Gene Health Project, providers gain a partner in WellSpan Health — and durable genetic insights they can use to guide safer, more personalized prescribing for years to come.