The National Institute for Health and Clinical Excellence (NICE) has issued its preliminary recommendations on the use of AstraZeneca’s antiplatelet medicine, Brilique (ticagrelor). In its Appraisal Consultation Document, NICE concludes that ticagrelor is a cost effective treatment option in adult patients with acute coronary syndromes in England and Wales. As such, NICE has recommended ticagrelor in combination with aspirin as a treatment option in adults with acute coronary syndromes.
In December last year, the European Medicines Agency approved ticagrelor for the prevention of atherothrombotic events in adult patients who have had a myocardial infarction or an episode of unstable angina. This includes patients managed medically, and those who are managed with percutaneous coronary intervention or coronary artery by-pass grafting.
Following this approval, the Scottish Medicines Consortium accepted ticagrelor for use in combination with aspirin for all three acute coronary syndrome patient groups in May 2011.
AstraZeneca welcomes this positive initial recommendation from NICE and will continue to work with the organisation to progress toward completion of the appraisal for ticagrelor. In the interim, the company will continue to engage the appropriate local hospital formulary committees, protocol committees and healthcare professionals to bring this important medicine to patients as soon as possible.
Kausik Ray, professor of Cardiovascular Disease Prevention, St George’s Hospital NHS Trust Research Centre, stated “Despite current treatment options, one in seven patients (14.8%) will die within 12 months following a heart attack. Ticagrelor has been demonstrated to reduce a patient’s likelihood of dying from an acute coronary event, or having another heart attack or episode of unstable angina in comparison to the current standard of care, clopidogrel. The provisional recommendations issued by NICE means that we are one-step closer to ensuring this life-saving medicine is available for the thousands of patients in England and Wales who could benefit from its use.”
Ticagrelor is the first in a new chemical class of oral antiplatelet medication. In the PLATO study, ticagrelor was shown to reduce the risk of repeat cardiac events when given to adult patients after a heart attack or an episode of unstable angina, in comparison to the most commonly-used treatment, clopidogrel. The benefit of ticagrelor seen in PLATO manifested in the first thirty days and accrued whilst treatment was continued for up to 12 months; reducing a patient’s relative risk of a repeat heart attack by 16% at one year in comparison to clopidogrel (ARR = 1.1%) and risk of cardiovascular death by 21% (absolute risk reduction = 1.1%).
Treatment with ticagrelor is recommended for up to 12 months. Premature discontinuation of any antiplatelet therapy, including ticagrelor, could result in an increased risk of cardiovascular death, or heart attack due to the patient’s underlying disease.
Patients taking ticagrelor generally had more bleeds that required further medical attention compared to the current standard of care. Ticagrelor was not associated with a significant increase in total major or fatal / life-threatening bleeds. An increase in dyspnoea was observed in PLATO (13.8% vs. 7.8%, p<0.001). Dyspnoea is ususally mild to moderate in intensity and often resolves without need for treatment discontinuation.
According to AstraZeneca’s records, in the UK, there were approximately 162,000 hospital admissions for heart attack and episodes of unstable angina between 2009-2010. According to Taylor et al, the total cost of the management of heart attacks and unstable angina in the UK is around £1.5 billion a year.
Final guidance for England and Wales, from NICE is expected later this year; however ticagrelor is currently available in the UK for healthcare professionals to prescribe in the interim in accordance with local guidance. NICE guidance is also expected to be adopted in Northern Ireland. Other oral antiplatelet medicines currently available in England and Wales include clopidogreland prasugrel.AstraZeneca will continue to work with NICE as part of the consultation process and look forward to the publication of the Final Appraisal Determination later this year.
Ticagrelor is approved in 35 countries, including in the European Union under the trade name Brilique and in Brazil, Canada and most recently Australia under the trade name Brilinta. The product currently has received price approvals in 16 countries and reimbursement authorisations in seven.
PLATO was a large, international (18,624 patients in 43 countries), head-to-head patient outcomes study of ticagrelor versus clopidogrel, designed to establish whether ticagrelor could achieve clinically meaningful cardiovascular and safety end points in acute coronary syndrome patients, above and beyond those afforded by clopidogrel.
The study demonstrated that treatment with ticagrelor with aspirin led to a greater reduction in the primary endpoint [a composite of death from vascular causes, heart attack or stroke] compared to patients who received clopidogrel with aspirin (16% relative risk reduction; absolute risk reduction 9.8% vs. 11.7% at 12 months). The study also demonstrated that treatment with ticagrelor with aspirin for 12 months was associated with a 21% relative risk reduction in cardiovascular death (absolute risk reduction 1.1%) compared to clopidogrel with aspirin at 12 months.
As with all oral antiplatelet medications, the use of ticagrelor can increase the risk of bleeding. In PLATO, there was no difference in overall major bleeding (11.6% vs. 11.2%, p=0.43) or in fatal/life-threatening bleeding episodes (5.8% vs. 5.8%, p = 0.70) between patients treated with ticagrelor with aspirin compared to those treated with clopidogrel with aspirin. However, non-coronary artery by-pass grafting major bleeding was more common with ticagrelor vs. clopidogrel (4.5% vs. 3.8%, p=0.03).