PHARMCLO Evaluates Genetic Screening to Inform the Selection of Antiplatelet Drugs in ACS Patients
March 11, 2018—The PHARMCLO trial demonstrated that patients with acute coronary syndrome (ACS) experienced a substantially lower rate of heart attack, stroke, death from cardiovascular causes, and major bleeding at 12 months if genetic information was used to inform the selection of their antiplatelet medication.
The findings were presented by Diego Ardissino, MD, in a Late Breaking Trial session at the American College of Cardiology's (ACC) 67th annual scientific session held March 10–12 in Orlando, Florida. This study was simultaneously published online by Francesca Maria Notarangelo, MD, et al in Journal of the American College of Cardiology.
The PHARMCLO study combined clinical characteristics with genetic information to inform the choice of P2Y12 receptor antagonist in patients with ACS. At 12 months, patients who underwent a genetic test to inform the choice of medication were 42% less likely to experience heart attack, stroke, or death from cardiovascular causes, or major bleeding (the trial's composite primary endpoint) compared with patients who did not undergo the genetic test.
In the ACC press release, Dr. Ardissino commented, "Selecting treatment on the basis of genetic data in addition to considerations concerning the patients' clinical characteristics may lead to a more personalized, and therefore more efficient, antiplatelet therapy, thus reducing both ischemic and bleeding risk."
He continued, "PHARMCLO is the first step of a new approach that will see a shift in emphasis away from trying to discover ever more potent antithrombotic drugs and toward ensuring that the right therapy is given to each individual patient." Dr. Ardissino is a cardiologist at Azienda Ospedaliero-Universitaria di Parma in Parma, Italy.
As summarized in the ACC announcement, the PHARMCLO investigators enrolled 888 patients hospitalized for ACS in Italy. Half were randomly assigned to receive standard clinical care, in which doctors prescribed clopidogrel, ticagrelor, or prasugrel based on the patient's clinical characteristics alone. The other half were assigned to receive a genetic test, the results of which doctors considered, along with clinical characteristics, when prescribing antiplatelet therapy.
At 12 months, the trial's composite primary endpoint had occurred in 25.9% of patients receiving standard care and 15.8% of patients who underwent the genetic test.
Genetic testing also resulted in different prescribing patterns. Whereas prasugrel was prescribed at similar rates in both groups, clopidogrel was prescribed significantly more frequently among those who did not undergo a genetic test and ticagrelor was prescribed significantly more frequently among those who did undergo a genetic test.
The investigators noted that previous studies have shown prasugrel and ticagrelor to be superior to clopidogrel at preventing ischemic events. However, prasugrel and ticagrelor, which are more potent, are also known to increase the risk of bleeding.
The findings suggest that having more information about a specific patient's likely response to clopidogrel can help doctors weigh this trade-off.
Several genes have been shown to affect enzymes that make clopidogrel more or less effective in preventing platelet aggregation. For this study, researchers developed an easy-to-use genetic screening tool, ST Q3, that provides information about these genes from a blood sample in just 70 minutes.
Dr. Ardissino explained, "As genotyping to select P2Y12 receptor antagonists in the setting of ACS cannot be delegated to centralized genetic laboratories for reasons of time, we designed the ST Q3 instrument for bedside genotyping as a low-cost, portable system for foolproof use by unskilled personnel."
As stated in the ACC announcement, the PHARMCLO investigators suggest the study findings offer a proof of concept that personalized genetic information can be used to inform treatment decisions and improve outcomes for people with ACS. Additional research would be needed to confirm the findings and incorporate genotyping into clinical practice for this patient population.
The PHARMCLO study stopped recruiting patients early after the Ethics Committee of Modena in Italy required the trial to be prematurely stopped because of the lack of in vitro diagnosis certification for the ST Q3 instrument. All of the patients were followed up as planned.