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Personalized approach to antiplatelet drug selection may improve clinical outcomes
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ORLANDO, Fla. — Selection of antiplatelet therapy based on genetic information in addition to a patient’s clinical characteristics reduced ischemic and bleeding complications in patients with ACS, researchers reported at the American College of Cardiology Scientific Session.
“Clopidogrel leads to substantial variability in patient responses, which limits its effectiveness. Part of this variability is of genetic origin,” Diego Ardissino, MD, director of the cardiology division at the Azienda Ospedaliero-Universitaria di Parma, Italy, and professor of cardiology at the University of Parma, said during a presentation. “The PHARMCLO study was designed to test the hypothesis that selecting antiplatelet therapy on the basis of a combination of genetic information and patients’ clinical characteristics would lead to better clinical outcomes in comparison with standard of care based on clinical characteristics alone.”
The randomized, multicenter trial included 888 unselected patients hospitalized for STEMI and non-STEMI who were assigned to treatment with a P2Y12 receptor antagonist based clinical characteristics or clinical characteristics (n = 440) and the presence of ABCB1, 2C19*2 or 2C19*17 genotypes (n = 448).
At 12 months, the primary outcome — a composite of CV death or first occurrence of nonfatal MI, nonfatal stroke or Bleeding Academic Research Consortium (BARC) 3- to 5-defined major bleeding — occurred less frequently in the pharmacogenomics arm vs. the standard-of-care arm (15.9% vs. 25.9%; HR = 0.58; 95% CI, 0.43-0.78; P < .001).
Additionally, fewer ischemic endpoints occurred in the pharmacogenomics arm compared with the standard-of-care arm (13% vs. 21.4%; HR = 0.57; 95% CI, 0.41-0.8; P < .001). There were also fewer bleeding endpoints in the pharmacogenomics arm, but the difference was not statistically significant (4.2% vs. 6.8%; HR = 0.62; 95% CI, 0.35-1.1; P = .1).
Notably, results showed a significant difference in frequency distribution of P2Y12 receptor antagonists in both study arms, with more patients receiving ticagrelor (Brilinta, AstraZeneca) in the pharmacogenomics arm (42.6% vs. 32.7%; P = .02) and more patients receiving clopidogrel in the standard-of-care arm (50.7% vs. 43.3%; P = .02). Prasugrel was used equally in both study arms.
The researchers also evaluated the primary endpoint in patients treated with clopidogrel. In this group, 24.7% patients in the pharmacogenomic arm vs. 35.4% in the standard-of-care arm experienced the primary endpoint (HR = 0.68; 95% CI, 0.47-0.97; P = .03).
Ardissino said this was a high-risk population, with the mean age at 71 years and more than one-quarter of patients aged older than 80 years. Twenty-one percent of patients had a previous MI, and nearly all patients had a typical rise and fall of cardiac enzyme. Revascularization was performed in 72% of patients, with the majority being treated with PCI.
Importantly, Ardissino noted that the researchers originally planned to enroll more than 3,600 patients. However, the trial was terminated early by the Ethics Committee of Modina because of the lack of in vitro diagnosis certification for the ST Q3 instrument — the tool used for genotyping patients.
The smaller-than-expected sample size due to early termination accounts for the wide confidence intervals, he said.
“The implementation of multiple genotyping to guide antiplatelet therapy in ACS is feasible across different institutions, and a more personalized approach to the selection of antiplatelet therapy may lead to clinically meaningful reduction in ischemic and bleeding complications,” Ardissino said. “Future studies of genotype-guided antiplatelet therapy are required to confirm these data and clarify the cost-efficacy of genotyping in the challenging setting of ACS before implementing it in everyday clinical practice.” – by Melissa Foster
References:
Ardissino D. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Notarangelo FM, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.02.029.
Disclosure: The researchers report no relevant financial disclosures.