New antiplatelet agent increases heart attack survival rate while reducing recurrence rate.

A new antiplatelet agent reduces the mortality and recurrence risks associated with heart attacks without increasing the risk of major bleeding. This has been shown by a large-scale international clinical study (PLATO) led by the Uppsala Clinical Research Center (UCR) at Uppsala University and Uppsala University Hospital and the Duke Clinical Research Institute in Durham, North Carolina, USA.

The definitive results from PLATO (A Study of Platelet Inhibition and Patient Outcomes) were presented today at the European Society of Cardiology Congress in Barcelona. The results were simultaneously published on the website of the New England Journal of Medicine. The study compared the effectiveness of a new antiplatelet agent, ticagrelor (Brilinta®) with that of clopidogrel (Plavix®), the standard heart attack medication.

The results show that treatment with the new agent, ticagrelor, reduced the risk of new cardiovascular events (CV mortality, heart attack or stroke) by 16 per cent, from 11.7 to 9.8 per cent (p<0.001), without increasing the risk of major bleeding complications. The improvement primarily involved a statistically significant reduction of the rates of CV mortality and heart attack, no difference being observed in the rate of stroke. The risk of thrombosis in stents, which are frequently involved in the treatment of heart attacks, was also reduced. These advantages were apparent at an early stage in treatment and increased as treatment progressed. Ticagrelor is accordingly the first antiplatelet agent shown to reduce CV mortality in connection with all forms of acute coronary syndrome (ACS). The results of the study entail that for every thousand ACS patients treated with ticagrelor rather than clopidogrel, 14 lives can be saved and 11 heart attacks and 8 stent thrombosis cases prevented, with no increase in theincidence of major bleeding.

"Ticagrelor is the first antiplatelet therapy to achieve a significant reduction in CV mortality in ACS patients versus clopidogrel and, perhaps most importantly, without an increase in major bleeding," comments Professor Lars Wallentin, Co-Chairman of the PLATO Executive Committee and director for the study. "PLATO has redefined what is possible in terms of preventing recurrent events in patients with acute coronary syndrome."

"The standard treatment is, for genetic reasons, not successful with all patients, and stent thrombosis is common where the full effect is not produced," says Associate Professor Stefan James, coordinator for the Swedish research centres participating in the study. "This risk is also reduced with the new agent."

The PLATO study confirms the results of earlier clinical studies involving ticagrelor, which demonstrated improved treatment efficacy without any increase in the incidence of major bleeding. The rate of major bleeding complications observed in connection with both treatment groups was independent of gender, weight and history of stroke/TIA. The group treated with ticagrelor evidenced a slight overall incidence of bleeding when minor as well as major bleeding was taken into account. Heart rhythm irregularities were more frequently observed during EKG monitoring of hospitalised patients treated with ticagrelor though not when such monitoring conducted in later treatment stages in patients' homes. The observed heart rhythm pauses were not associated with any symptoms or other negative consequences for patients treated with ticagrelor. An increase in transient shortness of breath was also observed with the ticagrelor treatment group, but only one in one hundred patients who received ticagrelor chose to discontinue medication due to this side effect.

KEY FACTS

About the PLATO study:
The PLATO study sought to determine whether using ticagrelor to treat ACS patients was associated with clinically meaningful advantages by comparing the efficacies of ticagrelor and the standard drug, clopidogrel, each in combination with aspirin. A total of 18,624 patients at 893 hospitals in 43 countries spread across the five continents participated in the study. Of these patients, 348 were treated in Sweden (46 at Uppsala University Hospital). Long-term antiplatelet treatment (spanning 6-12 months) with either ticagrelor (90 mg twice daily) or clopidogrel (75 mg daily) was initiated shortly after hospital admission. The study was led by an executive board with two co-chairmen, Professor Lars Wallentin of the Uppsala Clinical Research Center and Professor Robert Harrington of the Duke Clinical Research Institute in the U.S. The design of the PLATO study was published in the April 2009 edition of the American Heart Journal (James, S. et al., Am Heart J 2009; 157: 599-605).

About ticagrelor:
Ticagrelor is the first orally administrable agent that reversibly blocks the P2Y12 ADP receptor on platelets. Blocking of ADP receptors inhibits platelet activation, thereby reducing the risk of thrombosis. Ticagrelor (Brilinta®) is the first substance of a new class of chemicals, cyclopentyl-triazolo-pyrimidines, which are distinct from thienopyridines such as clopidogrel and prasugrel. Ticagrelor (Brilinta®) was developed and is manufactured by AstraZeneca.

About ACS:
ACS is an umbrella term for conditions involving sudden chest pain due to insufficiency in the blood supply to heart muscle secondary to arterial thrombosis. There are two primary categories of ACS: unstable angina, which does not damage heart muscle, and heart attacks (including less serious non-ST elevation and more serious ST elevation events), which are associated with permanent damage to heart muscle. ACS is the leading cause of heart-associated hospitalisation. One in three ACS patients dies, has another heart attack or requires hospitalisation within six months of the initial event. Increasing survival rates by preventing recurrences without damaging side effects is an important goal of clinical ACS research.

About the treatment of ACS:
The primary objectives of ACS treatment are restoring blood flow to the heart muscle and reducing the risk of recurrence. Depending on the severity of the condition, treatment may be limited to medication or include such surgical options as percutaneous coronary intervention (PCI), which involves opening a blocked artery by means of a balloon catheter and, frequently, insertion of an arterial prosthesis (stent) to maintain the opening, or coronary bypass, which aims to restore blood flow to the heart muscle by circumventing a blocked artery.

Contact: Lars Wallentin, Professor of Cardiology, Uppsala Clinical Research Center, mobile: +46-70-631 35 66 (currently in Barcelona)or Lars.Wallentin@ucr.uu.se

Please note that interviews with Professor Wallentin should be scheduled through Executive Assistant Anita Öström by calling +46-18-611 95 04 or (mobile) +46-70-296 04 40

Stefan James, Associate Professor, Cardiology, mobile: +46-70-594 44 04 (currently in Barcelona)or Stefan.James@ucr.uu.se