Precision Medicine Approach Could Improve Heart Disease Treatment

An international trial used genetic testing and precision medicine techniques to choose antiplatelet therapies for heart disease patients, lowering the chance of heart attack or stroke by 34 percent, according to a study published in JAMA.

Percutaneous coronary intervention (PCI) is a non-surgical procedure where physicians inflate a balloon and place a metal stent in narrowed heart arteries to improve blood flow to the heart. Placement of a balloon and metal stent inside a heart artery can irritate the blood vessel and cause it to clot, which can block the artery from being treated.

PCI patients are prescribed medications to stop their blood from clotting. The most common medication used is clopidogrel, which stops blood platelets from sticking together and prevents clots from forming. However, in almost a third of all patients, the gene required to activate clopidogrel, CYP2C19, does not work.

As a result, patients with this genetic variant may be at higher risk of experiencing adverse cardiovascular events, such as heart attack or stroke in the year following their procedure. Because current guidelines do not recommend genetic testing when prescribing clopidogrel, researchers set out to determine whether genetic testing would decrease cardiovascular complications after PCI.

Led by a team from Mayo Clinic and the Peter Munk Cardiac Center, the TAILOR-PCI trial studied 5,302 patients treated for heart artery blockage with one or more stents, and followed them for one year.

Researchers tested half the group for the CYP2C19 gene variation, and treated carriers with the alternative anti-platelet medication Ticagrelor. The team gave the rest of the group Clopidogrel, as well as the rest of the control group of patients who didn’t receive genetic testing before PCI.

The results showed that genetic testing led to a 34 percent reduction in serious adverse cardiac events, indicating the benefits of applying a precision medicine approach to heart disease treatment.

"The trial introduces the concept and validates the approach to personalized medicine when it comes to antiplatelet therapy, and therefore allows our physicians to potentially change their practice based on the needs of patients undergoing PCI," said Michael Farkouh, cardiologist and Multinational Clinical Trials Chair at the Peter Munk Cardiac Center. "This will potentially inform the kinds of therapies patients with heart disease are prescribed after PCI worldwide."

A post-hoc analysis of the trial also showed a nearly 80 percent reduction in the rate of adverse events in the first three months of treatment among patients who received genetically guided therapy compared with those who did not.

Since the study’s design in 2012, the standard of care following PCIs has greatly improved, the researchers noted. Drug-coated stents and other treatments have reduced the rate of adverse events for patients in a year, but at the same time made it difficult for the trial to reach its goal – a 50 percent reduction in adverse cardiovascular events at one-year post-procedure. The trial is currently undergoing an extended follow-up beyond the 12-month period.

Despite the fact that the study failed to produce results to the extent that the research team had intended, the findings reveal the benefits of applying a precision medicine approach to patients that have had PCIs.

"Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy, with approximately one third fewer adverse events in the patients who received genetically guided treatment compared with those who did not," said Naveen Pereira, Professor of Medicine and cardiologist at Mayo Clinic.