08 Sep 2020
Timing of oral P2Y12 inhibitor administration in non-ST elevation acute coronary syndrome
Selected in JACC by S. Brugaletta
What do you do in your daily practice: Do you use routine pre-treatment in NSTEMI patients? Have you modified your practice based on the new ESC guidelines?
References
Authors
Tarantini G, Mojoli M, Varbella F, Caporale R, Rigattieri S, Andò G, Cirillo P, Pierini S, Santarelli A, Sganzerla P, Cacciavillani L, Babuin L, De Cesare N, Limbruno U, Massoni A, Rognoni A, Pavan D, Belloni F, Cernetti C, Favero L, Saia S, Fovino LN, Masiero G, Roncon L, Gasparetto V, Ferlini M, Ronco F, Rossini R, Paoo Canova P, Trabattoni D, Russo A, Guiducci V, Penzo C, Tarantino F, Mauro C, Corrada E, Esposito G, Berti S, Martinato M, Azzolina D, Gregori D, Angiolillo DJ, Musumeci G and for the DUBIUS Investigators, on behalf of the Italian Society of Interventional Cardiology (SICI-GISE)
Reference
J Am Coll Cardiol. 2020 Aug 31. Epublished DOI:10.1016/j.jacc.2020.08.053
Published
August 2020
Link
Read the abstractReviewer
Latest contributions
Optical coherence tomography- vs angiography-guided coronary stent implantation in calcified lesions: the ILUMIEN IV trial Percutaneous coronary treatment with Bioadaptor implant vs drug-eluting stent : 2-year outcomes from BIOADAPTOR RCT Coronary revascularisation deferral based on quantitative flow ratio or fractional flow reserve: a post-hoc analysis of the FAVOR III Europe trialMy Comment
Why this study? – the rationale/objective
Oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration was not well defined at the time of the study.
How was it executed? – the methodology
It is a randomised, adaptive, open-label, multi-centre, clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention (PCI) were further randomised to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of a composite of death from vascular causes (death from cardiovascular causes or cerebrovascular causes and any death without another known cause), non- fatal myocardial infarction (MI), or non-fatal stroke and major or fatal bleeding (type 3, 4 and 5 on the Bleeding Academic Research Consortium [BARC] scale), at 30 days after randomisation.
What is the main result?
1449 patients were 1:1 randomised to downstream or upstream oral P2Y12 inhibitor administration. A prespecified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]). These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment).
Critical reading and the relevance for clinical practice
This study shows that in NSTEMI there is no difference in benefit in administrating ticagrelor before or after coronary angiography. In particular, the answer to this question was so futile that the trial was stopped before completing the planned enrollment of patients. This premature interruption was also caused by the fact that outcomes herein considered were better than expected.
This is something already seen in other trials which failed in their primary endpoints, which can be explained by the fact that NSTEMI care is better now than some years ago, mainly driven by an improvement of the overall health care of these patients. Moreover, time to coronary angiography was less than 23 hours, making any advantage of one strategy over the other theoretically very small, especially not taking into account peri-procedural myocardial infarction. The inclusion of such event in primary endpoint would have required an increase in study budget for event adjudication, which a study not driven by industry is unfortunately not able to afford.
Although the trial for all these reasons is not sufficient to confidently give a definite conclusion, the new 2020 ESC guidelines for NSTEMI treatment, presented a few days before the DUBIUS trial, helps us in the decision-making process of routine pre-treatment with DAPT. These guidelines, based on the ISAR-REACT 5 and ACCOAST trials, do not recommend administering routine pre-treatment of DAPT without knowing coronary anatomy with the highest class of evidence (IIIa).
Tell us what you do in your daily practice: Do you use routine pre-treatment in NSTEMI patients? Have you modified your practice based on the new ESC guidelines?
3 comments
I am worried about downgrading the recommendation to class III, As in our center there is only Clopidogrel available and if we give it just before PTCA after knowing the coronary anatomy ,there will be no enough platelet inhibition due to slow onsetand less potency of the drug .I think the policy of no pretreatment may be only for more potent P2Y12 inhibitors .What do you think ? Many thanks
I am worried about downgrading the recommendation to class III, As in our center there is only Clopidogrel available and if we give it just before PTCA after knowing the coronary anatomy ,there will be no enough platelet inhibition due to slow onsetand less potency of the drug .I think the policy of no pretreatment may be only for more potent P2Y12 inhibitors .What do you think ? Many thanks
We are still using DAPT in NSTEMI patients before proceeding for Coronary Angiography alongwith Preloading strategy.