Global platelet reactivity and high risk ACS patients

August 28, 2012

Global platelet reactivity is more effective than responsiveness to clopidogrel in identifying acute coronary syndrome (ACS) patients at high risk of ischemic events, according to research presented at ESC Congress 2012.

The results from the RECLOSE 2-ACS study were presented by Dr Rossella Marcucci from the University of Florence.

The Responsiveness to and Stent thrombosis 2 – ACS (RECLOSE 2-ACS) study is a prospective, observational, referral centre cohort study of 1,789 patients with acute coronary syndromes undergoing percutaneous (PCI) at the Division of Cardiology, Careggi Hospital, Florence, Italy.

Dual with aspirin and clopidogrel is the cornerstone of therapy in these patients to improve prognosis and reduce adverse cardiovascular events, stent thrombosis and .

"In recent years, we and other groups have focused our attention on the role of platelet inhibition," said Dr Marcucci.

"We found that a significant percentage of patients on clopidogrel therapy – the so-called nonresponders to clopidogrel – had a high platelet reactivity (HPR) on clopidogrel and a significantly higher risk of developing an adverse ischemic event at a follow-up of 2 years."

A number of genetic and acquired conditions are associated with a high platelet reactivity on clopidogrel. Carriers of a genetic variant (the CYP2C19*2 polymorphism), diabetics, older patients, females and patients with a reduced renal and have a higher risk of maintaining a high platelet reactivity on clopidogrel. In addition, the concomitant use of drugs such as (PPIs) is associated with a reduced metabolization of clopidogrel (which is a prodrug and needs to be metabolized to the active drug by the liver) and a high risk of high platelet reactivity.

The aim of the current study was to evaluate whether a high platelet reactivity due to nonresponsiveness to aspirin could also identify ACS patients at high risk of ischemic events. The investigators also evaluated whether the combination of aspirin and clopidogrel nonresponsiveness could identify high risk patients more effectively than one measure alone.

The researchers measured platelet reactivity in response to aspirin and clopidogrel in patients enrolled in the RECLOSE 2-ACS study. They found that approximately 12% of patients had a high platelet reactivity to aspirin and were therefore nonresponders. These patients had a significantly higher prevalence of an ischemic event or cardiac death at the 2 year follow-up (major adverse cardiac events [MACE]: Hazard Ratio [HR]=1.4 [1.0-1.8], p<0.04; Cardiac death: HR=1.7 [1.2-2.6],p=0.004).

The researchers calculated the net reclassification index (NRI), which is a method to define whether the addition of a new parameter increases the predictive value. Dr Marcucci said: "We found that adding the response to aspirin to the response to clopidogrel enabled us to recognize a higher number of patients at risk of ischemic events and cardiac events."

Approximately 9% of patients had high platelet reactivity (i.e. were nonresponders) to both clopidogrel and aspirin. This phenotype is known as global high platelet reactivity (GHPR).

GHPR was significantly associated with cardiovascular ischemic events and cardiac death in a Cox regression analysis (MACE: HR=1.8[1.2-3.0], p<0.01); Cardiac death: HR=1.5 [1.0-2.2], p=0.02). The analysis was adjusted for age, sex, body mass index, smoking, diabetes, hypertension, hypercholesterolemia, history of myocardial infarction, serum creatinine higher than 1.5 mg/dl, left ventricular ejection fraction <40%, Killip class III or IV at admission, 3-vessel coronary disease, use of drug eluting stents, total stent length, multivessel PCI and use of abciximab.

Dr Marcucci said: "These results show that global high platelet reactivity is the most effective parameter for identifying ACS patients at high risk of ischemic events."

She added: "This shifts the focus of risk stratification from response to clopidogrel to assessing response to both clopidogrel and aspirin. Responsiveness to both antiplatelet drugs should be assessed in all with ACS in order to identify and reduce their risk of ischemic events."

Explore further: Study examines platelet function testing for guiding antithrombotic treatment before PCI procedures

Related Stories

Study examines platelet function testing for guiding antithrombotic treatment before PCI procedures

September 20, 2011
Among patients with acute coronary syndromes undergoing a procedure such as angioplasty, those who received platelet function tests before receiving antithrombotic therapy to determine appropriate clopidogrel dosing and who ...

Results of the TRIGGER-PCI trial reported at TCT 2011

November 9, 2011
A clinical trial comparing prasugrel to clopidogrel for patients with high on-clopidogrel platelet reactivity (HCPR) following percutaneous coronary intervention (PCI) was ended early due to relatively few occurrences of ...

Antiplatelets: 1 person, 1 dose?

April 14, 2011
An international consortium of scientists, including major contributions from the Montreal Heart Institute, demonstrates that the "one-size fits all" strategy of uniformly doubling the dose of an antiplatelet drug, clopidogrel, ...

Lower achieved platelet reactivity associated with better cardiovascular

August 30, 2011
Compared to patients who had persistently high platelet reactivity, those who achieved low platelet reactivity, according to the VerifyNow P2Y12 Test, had a reduced incidence of cardiovascular death, heart attack and stent ...

Personalized antiplatelet treatment improves outcome after PCI

August 28, 2012
Personalized antiplatelet treatment leads to better outcomes than standard antiplatelet treatment in patients undergoing coronary stent implantation, according to results from the MADONNA study presented at ESC Congress 2012.

Recommended for you

How genes and environment interact to raise risk of congenital heart defects

October 19, 2017
Infants of mothers with diabetes have a three- to five-fold increased risk of congenital heart defects. Such developmental defects are likely caused by a combination of genetic and environmental factors. However, the molecular ...

Mouse studies shed light on how protein controls heart failure

October 18, 2017
A new study on two specially bred strains of mice has illuminated how abnormal addition of the chemical phosphate to a specific heart muscle protein may sabotage the way the protein behaves in a cell, and may damage the way ...

Newborns with trisomy 13 or 18 benefit from heart surgery, study finds

October 18, 2017
Heart surgery significantly decreases in-hospital mortality among infants with either of two genetic disorders that cause severe physical and intellectual disabilities, according to a new study by a researcher at the Stanford ...

Saving hearts after heart attacks: Overexpression of a gene enhances repair of dead muscle

October 17, 2017
University of Alabama at Birmingham biomedical engineers report a significant advance in efforts to repair a damaged heart after a heart attack, using grafted heart-muscle cells to create a repair patch. The key was overexpressing ...

Physically active white men at high risk for plaque buildup in arteries

October 17, 2017
White men who exercise at high levels are 86 percent more likely than people who exercise at low levels to experience a buildup of plaque in the heart arteries by middle age, a new study suggests.

High blood pressure linked to common heart valve disorder

October 17, 2017
For the first time, a strong link has been established between high blood pressure and the most common heart valve disorder in high-income countries, by new research from The George Institute for Global Health at the University ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.