A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI

Abstract

SummaryOutcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12 receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment period, the risk of bleeding became particularly prominent during the chronic course of therapy. It may therefore be a valid approach to substitute prasugrel for clopidogrel in the early phase of chronic antiplatelet treatment after PCI. In the Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, we aim to compare standard prasugrel therapy with a de-escalating antiplatelet treatment approach guided by platelet function testing (PFT). The study is an investigator-initiated European multicentre, randomised clinical trial in biomarker-positive ACS patients after successful PCI. Two thousand six hundred patients will be randomised prior to hospital discharge in a 1:1 fashion to either receive standard prasugrel therapy (control group) or de-escalating therapy (one-week prasugrel followed by one-week clopidogrel and PFT-guided maintenance therapy from day 14 after hospital discharge, monitoring group). Patients of the monitoring group with high on-clopidogrel platelet reactivity (HPR) based on Multiplate analyzer testing (HPR: ≥ 46U per consensus definition) will be switched back to prasugrel, whereas those without HPR (<46 U) will continue clopidogrel treatment. The overall study treatment duration will be one year in both groups. The primary endpoint of the study is net clinical benefit (combined incidence of cardiovascular death, myocardial infarction, stroke and bleeding ≥ grade 2 according to BARC criteria) one-year after randomisation. TROPICAL-ACS is the first large-scale, randomised controlled trial assessing the clinical value of a PFT-guided de-escalation of antiplatelet treatment in biomarker positive ACS patients undergoing PCI.ClinicalTrials.gov Identifier: NCT01959451

Role of genetic testing in patients undergoing percutaneous coronary intervention

“…It may be argued that these trials were flawed by target population, antiplatelet medications, platelet function assay, HPR cut-off values, timing of testing, among other variables, which were not adequate to test for the study hypothesis [125]. Indeed, lessons learned from these studies have led to the development of perhaps more appropriately designed trials, such as the TROPICAL-ACS which will determine whether individualizing antiplatelet therapy based on platelet function tests remains an arena to nurture further research [126]. …”

Guided de-escalation of DAPT in acute coronary syndrome patients undergoing percutaneous coronary intervention with BVS implantation: a post-hoc analysis from the randomized TROPICAL-ACS trial

“…Key exclusion criteria were a history of TIA or stroke and need for oral anticoagulation. More details on inclusion and exclusion criteria were published previously [ 1 ]. In this specific post-hoc analysis we investigated the study subgroup of patients who received an ABSORB (Abbott) bioresorbable vascular scaffold (BVS) during the index PCI procedure.…”

“…Two weeks after discharge all patients had an outpatient visit that included blood sampling for PFT on the Multiplate analyzer (Roche Diagnostics, Rotkreuz, Switzerland). Details of this whole-blood based method have been published previously and a status of HPR for this assay was defined according to the current consensus document of the Working Group on HPR by an ADPtest aggregation value of ≥ 46 U [ 1 , 15 ]. In the guided de-escalation group, testing results determined the further course of treatment.…”

“…The key secondary endpoint was defined as class ≥ 2 bleeding events at 12 months defined according to BARC criteria. Further details on study endpoints were reported previously [ 1 ].…”

“…In the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, a platelet function testing (PFT)-guided dual antiplatelet therapy (DAPT) de-escalation strategy with an early switch from prasugrel to clopidogrel was found to be equally effective and safe when compared to standard treatment with uniform and potent platelet inhibition in biomarker positive acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) [ 1 , 2 ]. Additionally, among younger ACS patients, there was a net clinical benefit from PFT-guided DAPT de-escalation, driven by a reduction in bleeding events during long-term treatment [ 3 ].…”