A recent study by the German Centre for Cardiovascular Research (DZHK), based on routine clinical data from a German health insurance provider, confirms the superior effectiveness of the antiplatelet drug Prasugrel over Ticagrelor in the treatment of acute coronary syndromes (ACS). The study confirms the findings of the randomised ISAR-REACT5 study on the efficacy and safety of both drugs and also shows how innovative database analyses can supplement randomised study results.
The DZHK-funded randomised controlled trial ISAR-REACT5, published in 2019, showed that Prasugrel is superior to Ticagrelor in patients with ACS. However, it was previously unclear whether these results could also be transferred to clinical practice. The research team used health insurance claims from 17,642 patients with ACS to investigate the ISAR-REACT5 question in a real-world setting.
In clinical practice, Prasugrel showed a significantly reduced risk of serious cardiovascular events (death, myocardial infarction, stroke) compared to Ticagrelor when the inclusion and exclusion criteria of the ISAR-REACT5 study were replicated in the database. The result is comparable to that of the randomised study, which also reported a significant risk reduction for Prasugrel compared to Ticagrelor.
With regard to the safety endpoint (severe bleeding), there was no significant difference between Prasugrel and Ticagrelor either in routine care or in the ISAR-REACT5 study. It should be emphasised that the results were more pronounced in patients with ST elevation myocardial infarction (STEMI). Here, Prasugrel was the superior treatment option both in the randomised study and in routine care.
‘The confirmation of our study results by this important database analysis is extremely gratifying,’ says Prof. Dr Adnan Kastrati from the German Heart Centre Munich, principal investigator of the randomised ISAR-REACT5 study. ‘The work shows how important it is to verify the generalisability of RCT results in clinical practice in order to further develop evidence-based care.’
Can observational studies replace clinical trials in the long term?
Could observational studies even replace clinical studies in cardiology in the future? This question is answered by Dr Nils Krüger from TUM University Hospital, German Heart Centre Munich, DZHK scientist and author of the study. ‘Our results show that a well-designed and carefully conducted database study can lead to similar clinical and regulatory decisions if the underlying data are fit-for-purpose, meaning they adequately represent the study population and healthcare setting. We also have a societal responsibility to analyse these large datasets and extract the evidence they contain’, explains Krüger.
The great advantage of routine data analyses is their efficiency: they use existing data, such as German health insurance claims in this case, and thus enable rapid and cost-effective implementation. The new approach is particularly relevant when randomised controlled trials, also known as RCTs, are difficult or impossible to conduct due to ethical or practical obstacles. ‘While RCTs are often based on optimal experimental conditions, observational studies reflect actual clinical practice. Our results confirm that Prasugrel is similarly effective and safe in routine care as it is in the controlled environment of a RCT,’ says Krüger.
A paradigm shift in evidence generation
With the increasing availability of routine data, which is also becoming widely accessible in Germany as a result of the Health Data Utilisation Act, the Munich research team is observing a paradigm shift in evidence generation. ‘If we systematically analyse the data to determine the circumstances under which they allow reliable conclusions to be drawn, we will be able to answer new, highly relevant questions with greater confidence - for example in areas where RCTs often provide insufficient conclusions, such as the question of the effectiveness of cardiovascular therapies specifically in women or in older, multimorbid patients,’ adds Krüger.
Building on the findings of the study presented, for which Krüger received a Young Investigator Award from the German Cardiac Society , the young physician is conducting research at Harvard Medical School in Boston, USA, to develop novel methods for deriving causal effects from routine data. This includes further research that emulates questions from randomized trials, the evaluation of the effectiveness and safety of new treatment strategies for rare cardiovascular diseases, as well as the use of artificial intelligence methods to predict individual treatment effects. ‘The aim of this work is to further improve cardiovascular care on the basis of practical evidence,’ says Krüger.
The study, published in JAMA Network Open, emphasises the importance of developing innovative studies that validate the results of RCTs in practice and evaluate the underlying data to generate novel evidence that guides clinical decision-making.
Original publication:
Ticagrelor vs Prasugrel for Acute Coronary Syndrome in Routine Care. Krüger N, et al., JAMA Network Open doi:10.1001/jamanetworkopen.2024.48389
Contact: Dr. Nils Krüger, TUM University Hospital, German Heart Centre Munich , nils.kruger(at)tum.de
