Personalized approach to selecting antiplatelet drugs improves outcomes

March 11, 2018

ORLANDO (March 11, 2018) -- Patients with acute coronary syndrome 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 in a study presented at the American College of Cardiology's 67th Annual Scientific Session.

Acute coronary syndrome is an umbrella term that encompasses heart attacks and unstable angina (acute chest pain caused by narrowed arteries). To reduce the risk of future ischemic events (caused by thrombosis, the blockage of a blood vessel by a blood clot), patients with acute coronary syndrome are prescribed a daily aspirin and one of several antiplatelet medications in a class known as P2Y12 receptor antagonists.

Three main P2Y12 receptor antagonists are available: clopidogrel, ticagrelor and prasugrel. In deciding which one to use, doctors weigh a patient's risk of ischemic events against the risk of uncontrolled bleeding. Previous research has indicated that patients' genes can affect how well these different drugs work in individual patients.

The study, called PHARMCLO, is the first to combine clinical characteristics with genetic information to inform the choice of P2Y12 receptor antagonist in patients with acute coronary syndrome. At 12 months, patients who received a genetic test to inform the choice of medication were 42 percent 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 receive the genetic test.

"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," said Diego Ardissino, MD, cardiologist at Azienda Ospedaliero-Universitaria di Parma, Italy, and the study's lead author. "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."

Researchers enrolled 888 patients hospitalized for acute coronary syndrome 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 percent of patients receiving standard care and 15.8 percent of patients receiving the genetic test.

Genetic testing also resulted in different prescribing patterns. While prasugrel was prescribed at similar rates in both groups, clopidogrel was prescribed significantly more frequently among those who did not receive a genetic test and ticagrelor was prescribed significantly more frequently among those who did receive a genetic test. 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.

"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.

Researchers 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 acute coronary syndrome. Further 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 (Italy) required the trial to be prematurely stopped due to the lack of in vitro diagnosis (IVD) certification for the ST Q3 instrument. All of the patients were followed up as planned.
The study was supported by Programma di Ricerca Regione-Università, Regione Emilia-Romagna, bando 2010-2012 Area 2 Ricerca per il Governo clinico, a program affiliated with Italy's regional health service.

This study was simultaneously published online in the Journal of the American College of Cardiology at the time of presentation.

The ACC's Annual Scientific Session, which is taking place March 10-12 in Orlando, brings together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow @ACCinTouch, @ACCMediaCenter and #ACC18 for the latest news from the meeting.

The American College of Cardiology is a 52,000-member medical society that is the professional home for the entire cardiovascular care team. The mission of the College is to transform cardiovascular care and to improve heart health. The ACC leads in the formation of health policy, standards and guidelines. The College operates national registries to measure and improve care, offers cardiovascular accreditation to hospitals and institutions, provides professional medical education, disseminates cardiovascular research and bestows credentials upon cardiovascular specialists who meet stringent qualifications.

American College of Cardiology

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to