A genetic test to inform decisions about what antiplatelet to use following percutaneous coronary intervention (PCI) significantly reduced the number of major cardiovascular or cerebrovascular events in a single-center study published in Circulation: Genomic and Precision Medicine.
Researchers retrospectively analyzed outcomes from 1,193 patients who underwent PCI and received dual antiplatelet therapy (DAPT) with aspirin and another drug at the University of North Carolina Cardiac Catheterization Laboratory. They used an algorithm to test for the CYP2C19 genotype in 72.8 percent of those patients because a loss of function (LOF) in those alleles has been shown to impair the effectiveness of clopidogrel, the most commonly prescribed addition to aspirin in DAPT. Two other P2Y12 receptors, prasugrel and ticagrelor, were available to use as alternatives to clopidogrel.
Lead author Craig R. Lee, PharmD, PhD, and colleagues found patients carrying LOF alleles who were prescribed ticagrelor demonstrated a 4.65-fold risk of major adverse cardiovascular or cerebrovascular events (MACCE) within one year of PCI versus those given alternative drugs. Those adverse events included death, myocardial infarction, angina, ischemic stroke, stent thrombosis and transient ischemic attack.
There was no significant difference in MACCE based on P2Y12 inhibitor type among those who didn’t carry the genetic mutation, and the risk for major bleeding was similar across groups.
“Using an algorithm based on genetic testing to guide treatment is sustainable and associated with better clinical outcomes in a real-world clinical practice, although it is difficult to consistently maintain,” Lee said in a press release. “Clinicians need to be aware of the increased risk of major adverse cardiovascular events associated with use of clopidogrel in patients receiving stents who carry either one or two copies of the mutation.”
The researchers noted their center struggled to consistently use the testing to inform decisions throughout the study period, but they didn’t analyze the specific reasons behind this problem.
“Although the specific factors that contributed to this variability over time were beyond the scope of the current investigation, the authors speculate that lack of automated clinical decision support within the electronic health records and recurrent clinician education may, in part, contribute to reduced sustainability of algorithm implementation over time,” Joshua P. Lewis, PhD, with the University of Maryland School of Medicine, wrote in a related editorial.
Limitations of the study include its retrospective design, that physicians were ultimately responsible for prescribing decisions—potentially introducing bias—and that there were data only on medication prescriptions, not adherence.
Despite these limitations, Lewis said more studies like this are needed to determine the cost-effectiveness of genotype-guided treatment strategies and to further prove their clinical use. It is also likely that other genetic variants play a role in the effectiveness of antiplatelet therapy for certain individuals, he pointed out. They just need to be identified.
“A more comprehensive understanding of interindividual variation in response to antiplatelet agents will be critical for improving cardiovascular pharmacotherapy, reducing therapeutic failure and adverse drug events, and improving patient outcomes,” Lewis wrote.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.