Prasugrel versus clopidogrel for ACS patients managed without revascularisation

August 27, 2012, European Society of Cardiology

The first trial to study the effect of platelet inhibition in patients with acute coronary syndromes managed medically without revascularisation has found no significant difference between prasugrel and clopidogrel in the prevention of death, myocardial infarction or stroke.

The findings, from the Targeted Platelet to Clarify the Optimal Strategy to Medically Manage (TRILOGY ACS) study, were presented today at a Hot Line session of ESC Congress 2012 in Munich.

TRILOGY ACS was double-blind, randomised trial in which the effect of prasugrel (10 mg daily) was compared with that of (75 mg daily) for up to 30 months of treatment in ACS under 75 years with or non-ST elevation myocardial infarction (non-STEMI) managed without revascularisation. All study subjects, who totaled 7243 in number, were taking aspirin, and the prasugrel dose was reduced to 5 mg daily for patients weighing less than 60 kilograms. The primary end point of the trial was , , or stroke. The study was performed at 966 sites in 52 countries.

Results showed that, through a median follow-up period of 17 months, the primary end point among participants under 75 years occurred in 13.9% of those treated with prasugrel and 16.0% of those treated with clopidogrel (HR 0.91; 95% CI 0.79-1.05; P=0.21). Similar results were observed in the overall patient population of 9326 patients, who included an additional 2083 patients aged 75 years or older in whom a reduced dose of prasugrel (5 mg daily) vs. clopidogrel (75 mg daily) was explored.

However, an unexpected, time-dependent treatment effect was observed with a trend for a lower risk of ischaemic events with prasugrel after 12 months among patients under 75 years of age. Furthermore, a pre-specified analysis which accounted for all multiple recurrent ischaemic events (not just the first event among all components of the primary end point) suggested a lower risk with prasugrel (HR 0.85; 95% CI 0.72-1.00; P=0.044).

The rates of major, life-threatening, fatal and intracranial bleeding were infrequent and similar in each treatment group, both in patients over 75 years and in the overall population. The frequency of non-haemorrhagic serious adverse events was also similar by treatment, except for a higher frequency of heart failure in the clopidogrel group.

As background to the study, the study's chairman, Professor E Magnus Ohman from Duke University Medical Center, Durham, USA, explained that the patient population of the TRILOGY ACS trial has not been exclusively studied before in a . Around 60% of ACS patients undergo revascularisation, but the remaining 40% are managed solely with drug therapy. "Patients who are medically managed are at higher risk for repeated cardiovascular-related events," said Professor Ohman. "So optimising medical therapy for these patients is extremely important."

The efficacy and safety of prasugrel and clopidogrel were first compared in the TRITON study of 2007 in ACS patients scheduled for PCI. This study found that prasugrel was associated with significantly lower rates of ischaemic events, including stent thrombosis, but with an increased risk of major bleeding. TRILOGY ACS, said Professor Ohman, was designed as a follow-up to the TRITON trial, "to see if prasugrel was just as effective in ACS patients who aren't getting coronary stents or coronary bypass surgery".

The TRILOGY ACS study did not find an increase in severe bleeding complications with prasugrel as seen in the TRITON study, albeit with modification of the prasugrel dose for low-body weight (weight <60 kilograms) and elderly patients.

"This trial is unique in that it studied a population we have not previously explored in such detail," said Professor Ohman. "The result being neutral raises many important questions. The fact that prasugrel appears safe - with no statistical increase in major bleeding - offers assurance of the prolonged safety of this therapy, which had been raised in previous trials."

Adding further comment on the results, Dr Matthew T. Roe, Associate Professor of Medicine, Division of Cardiology, Duke University Medical Center, said: "We studied the use of potent platelet inhibition for a longer duration of treatment than any previous trial in a previously under-studied population of ACS patients. While we did not achieve our primary objective, we showed no difference in serious bleeding complications between prasugrel and clopidogrel, and we observed several intriguing findings that we feel deserve further exploration."

Explore further: Anti-clotting drugs yield similar results

Related Stories

Anti-clotting drugs yield similar results

August 26, 2012
The first trial to study patients with acute coronary syndrome who do not undergo coronary stenting or bypass surgery found no significant difference between two anti-clotting drugs – prasugrel and clopidogrel – in preventing ...

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 ...

Safety and tolerability of the oral Xa inhibitor darexaban for secondary prevention after acute coronary syndromes

August 30, 2011
A phase II dose-finding study has found that the new oral Factor Xa inhibitor darexaban was associated with a two to four-fold increase in bleeding when added to dual antiplatelet therapy in patients following an acute coronary ...

Study reports validation of the first point-of-care genetic test in medicine, regarding use of antiplatelet therapy

March 28, 2012
A study published Online First by the Lancet reports the successful validation and clinical application of the first point-of-care genetic test in medicine. The test successfully identifies the CYP2C19*2 allele: a common ...

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 ...

Recommended for you

Researchers borrow from AIDS playbook to tackle rheumatic heart disease

January 22, 2018
Billions of US taxpayer dollars have been invested in Africa over the past 15 years to improve care for millions suffering from the HIV/AIDS epidemic; yet health systems on the continent continue to struggle. What if the ...

A nanoparticle inhalant for treating heart disease

January 18, 2018
A team of researchers from Italy and Germany has developed a nanoparticle inhalant for treating people suffering from heart disease. In their paper published in the journal Science Translational Medicine, the group describes ...

Starting periods before age of 12 linked to heightened risk of heart disease and stroke

January 15, 2018
Starting periods early—before the age of 12—is linked to a heightened risk of heart disease and stroke in later life, suggests an analysis of data from the UK Biobank study, published online in the journal Heart.

'Decorated' stem cells could offer targeted heart repair

January 10, 2018
Although cardiac stem cell therapy is a promising treatment for heart attack patients, directing the cells to the site of an injury - and getting them to stay there - remains challenging. In a new pilot study using an animal ...

Two simple tests could help to pinpoint cause of stroke

January 10, 2018
Detecting the cause of the deadliest form of stroke could be improved by a simple blood test added alongside a routine brain scan, research suggests.

Exercise is good for the heart, high blood pressure is bad—researchers find out why

January 10, 2018
When the heart is put under stress during exercise, it is considered healthy. Yet stress due to high blood pressure is bad for the heart. Why? And is this always the case? Researchers of the German Centre for Cardiovascular ...

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.