Study results support improved CV outcomes with ticagrelor in real-world practice
9 April 2018
AstraZeneca today welcomed the publication of a new real-world analysis of more than 45,000 heart attack survivors, in Heart,1 suggesting treatment with BRILINTA (ticagrelor) plus low dose aspirin, compared to clopidogrel plus low dose aspirin, is associated with an 18% reduction of risk (adjusted hazard ratio (HR 0.82 (0.7 to 0.97)) over one year for the composite endpoint of death, heart attack or stroke, in patients with moderate kidney disease (as defined by estimated glomerular filtration rate (eGFR) of 30 - 60ml/min).1
The results from PRACTICAL, an analysis of data from the ongoing SWEDEHEART quality registry, provide real-world evidence that patients who survived a heart attack (also known as myocardial infarction (MI)) and have moderate kidney disease, had a lower risk of experiencing future cardiovascular (CV) events when treated with ticagrelor rather than clopidogrel.1,2,3
Cardiovascular disease (CVD) is a leading cause of death and morbidity in patients with compromised kidney function4,5 and an estimated 25 – 40% of people who experience a heart attack have kidney disease.6,7,8 AstraZeneca is committed to learning more about the links and commonality of the underlying mechanisms driving both CKD and CVD, and this analysis in Heart offers important insights into the safety and efficacy of antiplatelet therapy in patients with both CVD and CKD.
Dr. Robert Edfors, Karolinska University Hospital and Karolinska Institute, and study author, said: “This analysis of SWEDEHEART data is significant because it complements clinical trial data by providing outcomes following antiplatelet therapy in everyday clinical practice. A large proportion of patients with MI also have kidney disease and these results show that ticagrelor, as compared to clopidogrel, was associated with significantly lower risk of ischaemic outcomes in patients with moderate renal dysfunction.”1,10,11
Ticagrelor, compared to clopidogrel, was associated with a significantly lower risk of the combined outcome of time to death, readmission due to stroke or MI at one year, but with a higher bleeding risk, especially in patients with severely reduced renal function.1 In patients with better kidney function, eGFR≥60*, the adjusted risk reduction for the primary endpoint was 13% (hazard ratios (HR) 0.87 (95% CI: 0.76-0.99)), 18% for eGFR30-60, and 5% for eGFR<30 (HR 0.95 (0.69-1.29)).1 However, with only 1,735 patients in the eGFR<30 group, the confidence intervals were wide, which makes it more difficult to assess differences between the patients on ticagrelor and those on clopidogrel.1
PRACTICAL is a real-world observational cohort study in 45,206 MI patients who were discharged on either ticagrelor or clopidogrel, against a background of aspirin, between January 1, 2010, and December 31, 2013 and recorded in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies) quality registry.1 The primary outcome was the composite of time to death, readmission due to stroke or MI at one year.1 Patients who underwent revascularisation with coronary artery bypass grafting were excluded from the analysis.1
While positive benefits of ticagrelor treatment in patients with kidney disease were seen in this study, ticagrelor was associated with more bleeding events.1 However, the authors note that the study’s findings support the notion that the proven benefit of ticagrelor observed in the clinical trial results can be applied in a real-world setting.1,2,3
NOTES TO EDITORS
About Brilinta (ticagrelor)
Brilinta is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclo-pentyl-triazolo-pyrimidines (CPTPs). Brilinta works by inhibiting platelet activation and has been shown to reduce the rate of atherothrombotic CV events, such as heart attack or CV death, in patients with acute coronary syndromes (ACS).
Brilinta, co-administered with aspirin, also known as acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with ACS, or for patients with a history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event.
PRACTICAL evaluated outcomes in a large population of real-world acute coronary syndrome (ACS) patients treated with ticagrelor or clopidogrel in Sweden who were enrolled into the SWEDEHEART registry. It included consecutive survivors of an acute MI, discharged on DAPT with either ticagrelor or clopidogrel, between 2010 and 2013. Primary outcome was the composite of death, readmission for MI or stroke at one year. Secondary outcomes included the individual components of the primary outcome. Bleeding outcomes were readmission to hospital with bleeding and bleeding in-hospital in those undergoing PCI.
PRACTICAL lead researchers are part of the TOTAL-AMI network of researchers with collaborators based at Uppsala Clinical Research Center, Uppsala, Danderyd University Hospital, Karolinska University Hospital and Karolinska Institute, Sweden, as well as the National Heart Centre in Singapore.
About AstraZeneca in Cardiovascular, Renal & Metabolism
Cardiovascular, renal and metabolism is one of AstraZeneca’s main therapy areas and platforms for future growth.
By following the science to understand more clearly the underlying links between the heart, kidney and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of these diseases and even regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CVRM health for millions of patients worldwide.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
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2 Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045–57.
3 James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 2010;122:1056-67.
4 Subbiah AK, Chhabra YK, Mahajan S. Cardiovascular disease in patients with chronic kidney disease: a neglected subgroup. Heart Asia. 2016;8:56-61.
5 Thompson S, James M, Wiebe N, et al. Cause of Death in Patients with Reduced Kidney Function.J Am Soc Nephrol. 2015;26:2504-11.
6 Fox CS, Muntner P, Chen AY, et al. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation. 2010;121:357-65.
7 Szummer K, Lundman P, Jacobson SH, et al. Influence of renal function on the effects of early revascularization in non-ST-elevation myocardial infarction: data from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Circulation. 2009;120:851-8. 9
8 Goldenberg I, Subirana I, Boyko V, et al. Relation between renal function and outcomes in patients with non-ST-segment elevation acute coronary syndrome: real-world data from the European Public Health Outcome Research and Indicators Collection Project. Arch Intern Med. 2010;170:888-95.
9 Wagner L-A, Tata AL, Fink JC. Patient Safety Issues in CKD. Am J Kidney Dis. 2015;66:159-169.
10 National Institutes of Health. Chronic Kidney Disease and Kidney Failure. Available at: https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=34 Accessed March 2018.
11 Ojo A. Addressing the Global Burden of Chronic Kidney Disease Through Clinical and Translational Research. Transactions of the American Clinical and Climatological Association. 2014; 125: 229-246.