Genetic information to guide antiplatelet selection after ACS can improve outcomes
THE PHARMCLO STUDY: A Prospective, Randomised, Multicentre Study Of A Pharmacogenomic Approach To The Selection Of Antiplatelet Therapy In Acute Coronary Syndromes
Presented at ACC.18 by Diego Ardissino (Azienda Ospedaliero - Universitaria di Parma, Italy)
The efficacy of the antiplatelet agent clopidogrel in patients with acute coronary syndrome (ACS) is hampered due to interpatient response variability. Choice of P2Y12 receptor antagonist treatment is normally based on a doctor’s assessment of a patient’s risk of ischemic events and the risk of uncontrolled bleeding. 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, which provides information about these genes from a blood sample, within 70 minutes at each patient’s bedside.
The PHARMCLO study aimed to evaluate a more personalized approach to choosing a P2Y12 receptor antagonist in patients with ACS. The study combined clinical characteristics with genetic information to inform the choice of medication. 888 Patients hospitalized for ACS in 13 centers in Italy were randomized to either receive standard clinical care, in which doctors prescribe clopidogrel, ticagrelor or prasugrel based on clinical characteristics alone, or to receive a genetic test (testing for ABCB1, 2C19*2, 2C19*17), the result of which were considered along with clinical characteristics, before prescribing antiplatelet therapy. The primary endpoint at 12 months was a composite of myocardial infarction, stroke, CV death or major bleeding (BARC 3-5).
- In the standard of care arm, 50.7% patients were prescribed clopidogrel, 8.4% received prasugrel, 32.7% received ticagrelor and 8.2% did not get a P2Y12 inhibitor. In the pharmacogenomics arm 43.3% received clopidogrel, 7.6% prasugrel, 42.6% ticagrelor and 6.5% received no P2Y12 inhibitor.
- The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomics arm and in 114 (25.9%) in the standard of care arm.
- Patients receiving a genetic test showed a 42% reduction of the primary endpoint as compared with the standard of care treatment arm (HR: 0.58, 95%CI: 0.43-.078, P<0.001). The reduction of the primary endpoint was mostly driven by a reduction of non-fatal MI (21 vs. 47, HR: 0.42, 95%CI: 0.25-0.70).
- In patients treated with clopidogrel, the primary endpoint was reduced by 32% in the pharmacogenomics arm as compared with controls (HR: 0.68, 0.47-0.97, P=0.03).
This study showed that the implementation of genotyping to guide the antiplatelet therapy in ACS is feasible across different institutions and that it resulted in different prescribing patterns. A more personalized approach to the selection of antiplatelet therapy may lead to a clinically meaningful reduction in ischemic and bleeding complications. Future studies of genotype-guided antiplatelet therapy should confirm these data and clarify the cost-efficacy of genotyping in the challenging setting of ACS.
In a press release, the presenter Diego Ardissino said “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.” And, “As genotyping to select P2Y12 receptor antagonists in the setting of acute coronary syndromes 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,” Ardissino said.
Our coverage of ACC.18 is based on the information provided during the congress.