Data results of the PLATelet inhibition and patient Outcomes (PLATO) trial's health economics substudy

AstraZenecaAstraZeneca today announced that full data results of the PLATO health economics substudy, which have been published online in the European Heart Journal, demonstrate that even at a higher drug cost and incremental cost per acute coronary syndromes (ACS) patient, ticagrelor (known as BRILIQUE in the European Union and BRILINTA elsewhere) numerically lowered non-drug healthcare costs versus generic clopidogrel and is cost-effective.

The cost-effectiveness of ticagrelor was driven by the mortality benefit seen in the pivotal PLATO trial, which showed ticagrelor was cost-effective across all major patient subgroups.

The analysis used in the health economics substudy included the Swedish costs for both ticagrelor and generic clopidogrel and found that though treating ACS patients with ticagrelor costs an additional average of €96 per patient/year, treatment with ticagrelor resulted in a 21% mortality benefit and lower healthcare costs at 12 months as compared to generic clopidogrel.

"What's striking about these data is that they showed treatment with ticagrelor was cost-effective for ACS patients, compared to the lower-priced generic option, because the medicine improved survival, reduced recurrent events and reduced other healthcare costs," said Lars Wallentin, Professor Cardiology Uppsala Clinical Research Centre.

An initial analysis from the PLATO HECON substudy on resource utilization and cost was first presented in November 2010 at the American Heart Association annual meeting in an abstract presentation called, Health Economics in the PLATelet inhibition and patient Outcomes (PLATO) Randomised Trial: Report on Within Trial Resource Use Patterns. This analysis excluded drug costs and concomitant drugs and did not account for the mortality data.

Following was a presentation at the 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) annual meeting that showed the overall cost impact of using ticagrelor instead of generic clopidogrel was cost-effective. The newly published data set included cardiovascular events, costs and quality-of-life data, drug costs and long-term data in the analyses and assessed the long-term cost-effectiveness of treating ACS patients for 12 months with ticagrelor and aspirin according to the EU label. In the analysis, ticagrelor was associated with a quality-adjusted life year (QALY) gain of 0.1316 at a lifetime incremental cost of €362, yielding a cost per QALY gained as compared to clopidogrel of €2,372.

Cost per QALY is an important measure used by national governments and their reimbursement agencies to assess cost-effectiveness of medical treatments. In order to prioritise treatments, the long-term costs and health outcomes of different treatment strategies are assessed and compared. While no universal threshold for cost-effectiveness exists, generally, a cost per QALY in the range of €25,000 ($33,000) to €38,000 ($50,000) is considered cost-effective.

The PLATO health economics data is part of a prospectively designed substudy of PLATO designed to help address important questions related to the access and affordability of ticagrelor around the world. To date, ticagrelor has received positive reimbursement recommendations in 25 countries, including European markets such as the UK, Germany and Italy.

PLATO (PLATelet Inhibition and Patient Outcomes) was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of ticagrelor versus clopidogrel, both given in combination with aspirin. The study was designed to establish whether ticagrelor could achieve a clinically meaningful reduction in cardiovascular (CV) events in acute coronary syndrome (ACS) patients, above and beyond that afforded by clopidogrel.

PLATO demonstrated that treatment with ticagrelor led to a greater reduction in the primary end point - a composite of CV death, myocardial infarction (MI), or stroke - compared to patients who received clopidogrel [9.8% vs. 11.7% at 12 months; 16% relative risk reduction (RRR); 95% CI, 0.77 to 0.92; p<0.001]. The difference in treatments was driven by CV death and MI with no difference in stroke. The absolute difference in treatment benefit versus clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continued to diverge throughout the 12-month treatment period [1.9% absolute risk reduction (ARR)].

The PLATO study also demonstrated that treatment with ticagrelor for 12 months was associated with a 21% RRR in CV death (4% vs. 5.1%; 1.1% ARR; p=0.001) and a 16% RRR in MI compared to clopidogrel at 12 months (5.8% vs. 6.9%; 1.1% ARR; p<0.005).

An analysis of PLATO formed the basis of the recommendation in all of the approved ticagrelor labels that patients taking ticagrelor should also take a low-maintenance dose of aspirin daily, unless specifically contraindicated.

With ticagrelor, there was no increase in total major bleeding, the primary safety endpoint, over the course of one year of treatment (11.6% for ticagrelor vs. 11.2% for clopidogrel; p=0.43), nor in fatal bleeding (0.3% in both groups; p=0.66). Non-coronary artery bypass graft (CABG)-related major bleeding was more common with ticagrelor compared to clopidogrel (4.5% vs. 3.8%; p=0.03), along with non-CABG-related major + minor bleeding (8.7% vs 7.0%). Dyspnoea was reported in 14% of patients treated with ticagrelor and in 8% of patients treated with clopidogrel (p<0.001), but most events were mild and transient.

About ticagrelor
Ticagrelor is an oral antiplatelet treatment for acute coronary syndromes (ACS). Ticagrelor is a direct-acting P2Y12 receptor antagonist in a new chemical class called cyclopentyltriazolopyrimidines (CPTPs).

Ticagrelor is approved in 79 countries, including in the European Union under the trade name BRILIQUE and in the United States, Canada, Brazil, Australia and Russia under the trade name BRILINTA.

BRILINTA and BRILIQUE are trademarks of the AstraZeneca group of companies. For detailed information regarding ticagrelor, please refer to the local Summary of Product Characteristics.

About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.